Title of Invention

SYNTHETIC POLYSACCARIDES, PROCESS FOR THEIR PREPERATION AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

Abstract Synthetic polysaccarides. process for their preperation and pharmaceutical compositions containing them The present invention relates to synthetic polysaccharides comprising a region for binding to antithrombin III consisting of a sequence of five monosaccharides bearing in total two carboxylic acid functions and at least four sulpho groups, this region being bound directly at its non-reducing end by a thrombin-binding region comprising a sequence of 10 to 25 monosaccharide units chosen from hexoses, pentoses or deoxy sugars in which the hydroxyl groups are, independently, etherified with a (C1- C6) alkyl group or esterified in the form of sulpho groups, as well as its salts, in particular its pharmaceutically acceptable salts.
Full Text

The present invention relates to novel synthetic polysaccharides possessing the















anticoagulant ^ and antithrombotic







pharmacological activities of heparin.












WE CLAIMS
1. Synthetic polysaccharide comprising a region for binding to antithrombin III consisting of a sequence of five monosaccharides bearing in total two carboxylic acid functions and at least four sulpho groups, this region being bound directly at its non-reducing end by a thrombin-binding region comprising a sequence of 10 to 25 monosaccharide units chosen from hexoses, pentoses or deoxy sugars in which the hydroxyl groups are, independently, etherified with a (C^-Cg) alkyl group or esterif ied in the form of sulpho groups, as well as its salts, in particular its pharmaceutically acceptable salts.
2. Polysaccharide according to Claim 1, of formula:
in which
- the wavy line denotes a bond either below or above
the plane of the pyranose ring,

denotes a polysaccharide Po containing n identical or different monosaccharide units, which is linked via its anomeric carbon to Pe,

is a diagrammatic representation of a monosaccharide unit of pyranose structure chosen from

hexoses, pentoses and the corresponding deoxy sugars, this unit being linked via its anomeric carbon to another monosaccharide unit, and the hydroxyl groups of this unit being substituted with identical or different groups -X, the groups X being chosen from (C1-C5)alkyl groups and sulpho groups,
n is an integer from 10 to 25,
Pe represents a pentasaccharide of structure:

R1 represents a (C1-C6)alkyl or a sulpho group, -R1a represents Ra or constitutes, with the oxygen, atom to which it is linked and the carbon atom bearing the carboxylic function on the same ring, a group

R represents a (C1-C6)alkyl group,
W represents an oxygen atom or a methylene group, or one of their salts, in particular a salt which is pharmaceutically acceptable.
3. Salt of a polysaccharide according to Claim 2,
in which the cation is chosen from cations of alkali
metals, in particular sodium and potassium.
4. Polysaccharide and salt according to either of
Claims 2 and 3, of formula:



denotes a particular family of polysacch-arides Po, linked via their anomeric carbon to Pe as defined for (I) ,

is as defined for (I) ,
the OXs are as defined for (I) and, for the same monosaccharide, may be identical or different,
the monosaccharides contained in []^ form a disaccharide repeated m times, the monosaccharides contained in [], form a disaccharide repeated t times,
m ranges from 1 to 8, t ranges from 0 to 5 and p ranges from 0 to 1, it being understood that 5 and their salts, in particular their pharmaceutically acceptable salts.
5. Polysaccharide and salt according to either of Claims 2 and 3, of formula:



Ill
denotes a particular family of polysaccharides Po, linked via their anomeric carbon to Pe as defined for (I),
is as defined for (I),
the OXs are as defined for (I) and, for the same monosaccharide, may be identical or different,
the monosaccharide contained in [].. is repeated m' times, the monosaccharide contained in []. is repeated t' times and the monosaccharide contained in []p. ia repeated p' times,
m' ranges from 1 to 5, t' ranges from 0 to 24 and p' ranges from 0 to 24, it being understood that 10 and their salts, in particular theiir pharmaceutically acceptable salts.
6. Salt according to either of Claims 2 and 2, the
anion, of which has the formula:

in which t represents 5, 6 or 7, and the cation being a pharmaceutically acceptable monovalent cation, as well as their corresponding acids.
7. Salt according to either of Claims 2 and 3, the
anion of which has the formula:


in which t represents 5, 5 or 7, and where the cation is a pharmaceutically acceptable monovalent cation, as well as their corresponding acids.
8. Salt according to either of Claims 2 and 3, the
anion of which has the formula:

in which m represents 1, 2 or 3 and t represents 2, 3, 4 or 5, and where the cation is a pharmaceutically acceptable monovalent cation, as well as their corresponding acids.
9. Polysaccharides chosen from:
• Methyl 0-(3-O-methyl-2,4,6-tri-O-sulpho-a-D-
glucopyranosyl)-(1-4)-O-(3-O-methyl-2,6-di-O-sulpho-β-
D-glucopyranosyl)-(1-4)-[0-(3-O-methyl-2,6-di-O-sulpho-
a-D-glucopyranosyl)-(1-4)-O-(3-O-methyl-2,6-di-O-
sulpho-(3-D-glucopyranosyl) - (1-4) ] 4-O- (2, 3-di-O-methyl-6-
0-sulpho-a-D-glucopyranosyl) - (1-4) -O- (2, 3-di-O-methyl-
P-D-glucopyranosyluronic acid)-(1-4)-O-(2,3,6-tri-O-
sulpho-a-D-glucopyranosyl)-(1-4)-O-(2,3-di-O-methyl-a-
L-idopyranosyluronic acid)-(1-4)-2,3,6-tri-O-sulpho-a-
D-glucopyranoside, sodium salt
• Methyl 0-(3-O-methyl-2,4,6-tri-O-sulpho-a-D-
glucopyranosyl)-(1-4)-O-(3-O-methyl-2,6-di-O-sulpho-β-
D-glucopyranosyl)-(1-4)-[0-(3-O-methyl-2,6-di-O-sulpho-
a-D-glucopyranosyl)-(1,4)-O-(3-O-methyl-2,6-di-O-sulpho-β-D-glucopyranosyl)-(l-4)]5-O-(2, 3-di-O-methyl-G-O-sulpho-a-D-glucopyranosyl) -(1-4)-O-(2,3-di-O-methyl-p-D-glucopyranosyluronic acid)-(1,4)-O-(2,3,6-tri-O-sulpho-a-D-glucopyranosyl)-(1-4)-O-(2,3-di-O-methyl-a-

L-idopyranosyluronic acid) - (1-4) -2,3, 6-tri-O-sulpho-α-D-glucopyranoside, sodium salt
• Methyl 0-(3-O-methyl-2,4,6-tri-O-sulpho-α-D-glucopyranosyl)-(1-4)-O-(3-O-methyl-2,6-di-O-sulpho-β-D-glucopyranosyl)-(1-4)-[0-(3-O-methyl-2,6-di-O-sulpho-a-D-glucopyranosyl)-(1-4)-O-(3-O-methyl-2,6-di-O-sulpho-β-D-glucopyranosyl)-(l-4)]s-O-(2, 3-di-O-methyl-G-O-sulpho-α-D-glucopyranosyl) -(1-4)-O-(2,3-di-O-methyl-P-D-glucopyranosyluronic acid) -(1-4)-O-(2,3,6-tri-O-sulpho-α-D-glucopyranosyl)-(1-4)-O-(2,3-di-O-methyl-α-L-idopyranosyluronic acid) -(1-4)-2,3,S-tri-O-sulpho-α-D-glucopyranoside, sodium salt
• Methyl 0-(2,3-di-O-methyl-4,6-di-O-sulpho-α-D-glucopyranosyl)-(1-4)-[0-(2,3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl)-(1-4)-] -O-(2,3-di-O-methyl-β-D-glucopyranosyluronic acid)-(1,4)-O-(2,3,6-tri-O-sulphO" a-D-glucopyranosyl)-(1-4)-O-(2,3-di-O-methyl-α-L-idopyranosyluronic acid)-(1-4)-2,3,6-tri-O-sulpho-α-D-glucopyranoside, sodium salt
• Methyl 0-(2,3-di-O-methyl-4,6-di-O-sulpho-α-D-glucopyranosyl)-(1-4)-[O-(2,3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl)-(1-4)-] 13-O-(2,3-di-O-methyl-β-D-glucopyranosyluronic acid)-(1-4)-O-(2,3,6-tri-O-sulpho-a-D-glucopyranosyl)-(1-4)-O-(2,3-di-O-methyl-α-L-idopyranosyluronic acid)-(1-4)-2,3,6-tri-O-sulpho-α-D-glucopyranoside, sodium salt
• Methyl 0-(2,3-di-O-methyl-4,S-di-O-sulpho-α-D-glucopyranosyl)-(1-4)-[0-(2,3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl)-(1-4)-] 15-O-(2,3-di-O-methyl-β-D-glucopyranosyluronic acid)-(1-4)-O-(2,3,6-tri-O-sulpho-a-D-glucopyranosyl)-(1-4)-O-(2,3-di-O-methyl-α-L-idopyranosyluronic acid)-(1-4)-2,3,6-tri-O-sulpho-α-D-glucopyranoside, sodium salt
• Methyl 0-(3-O-methyl-2,4,6-tri-O-sulpho-α-D-glucopyranosyl)-(1-4)-O-(3-O-methyl-2,6-di-O-sulpho-β-D-glucopyranosyl)-(1-4)-[0-(3-O-methyl-2,6-di-O-sulpho-a-D-glucopyranosyl)-(1-4)-O-(3-O-methyl-2,6-di-O-sulpho-β-D-glucopyranosyl)-(l-4)]2-[
O-(2,3, 6-tri-O-methyl-α-D-glucopyranosyl)-(l-4)-O-(2,3,6-tri-O-methyl-

p-D-glucopyranosyl)-(l-4)]2-O-2,3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl)-(l-4)-O-(2,3-di-O-methyl-β-D-glucopyranosyluronic acid) -(1-4) -O-(2,3,6-tri-O-sulpho-α-D-glucopyranosyl)-(1-4)-(2,3-di-O-methyl-α-L-idopyranosyluronic acid)-(l-4)-2,3,6-tri-O-sulpho-α-D-glucopyranoside, sodium salt
o Methyl 0-(3-O-methyl-2,4,5-tri-O-sulpho-α-D-glucopyranosyl) - (1-4) -O- ( 3-O-methyl-2 , 6-di-O-sulpho-|3-D-glucopyranosyl)-(1-4)-[0-(3-O-methyl-2,6-di-O-sulpho-a-D-glucopyranosyl ) -(1-4)-O-(3-O-methyl-2,5-di-O-sulpho-β-D-glucopyranosyl) -(l-4)]2-[0-(2,3,6-tri-O-methyl-α-D-glucopyranosyl)-(l-4)-O-(2,3,6-tri-O-methyl-p-D-glucopyranosyl)-(l-4)]3-O-2,3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl)-(1-4)-O-(2,3-di-O-methyl-β-D-glucopyranosyluronic acid)-(1-4)-O-(2,3,6-tri-O-sulpho-α-D-glucopyranosyl)-(1-4)-(2,3-di-O-methyl-α-L-idopyranosyluronic acid)-(1-4)-2,3,6-tri-O-sulpho-α-D-glucopyranoside, sodium salt
o Methyl 0-(3-O-methyl-2,4,6-tri-O-sulpho-α-D-glucopyranosyl) - (1-4)-O-(3-O-methyl-2,6-di-O-sulpho-β-D-glucopyranosyl)-(1-4)-O-(3-O-methyl-2,6-di-O-sulpho-a-D-glucopyranosyl) - (1-4)-O-(3-O-methyl-2,6-di-O-sulpho-β-D-glucopyranosyl) -(l-4)-[0-(2,3,6-tri-O-methyl-α-D-glucopyranosyl)-(l-4)-O-(2,3,6-tri-O-methyl-p-D-glucopyranosyl)-(l-4)]4-O-2,3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl)-(1-4)-O-(2,3-di-O-methyl-β-D-glucopyranosyluronic acid)-(l-4)-O-(2,3,6-tri-O-sulpho-α-D-glucopyranosyl)-(1-4)-(2,3-di-O-methyl-α-L-idopyranosyluronic acid)-(1-4)-2,3,6-tri-O-sulpho-α-D-glucopyranoside, sodium salt
o Methyl 0-(3-O-methyl-2,4,6-tri-O-sulpho-α-D-glucopyranosyl) -(1-4)-O-(3-O-methyl-2,6-di-O-sulpho-β-D-glucopyranosyl)-(1-4)-O-(3-O-methyl-2,6-di-O-sulpho-a-D-glucopyranosyl) - (1-4)-O-(3-O-methyl-2,6-di-O-sulpho-β-D-glucopyranosyl)-(l-4)-[0-(2,3,6-tri-O-methyl-α-D-glucopyranosyl)-(l-4)-O-(2,3,6-tri-O-methyl-p-D-glucopyranosyl)-(1-4)13-O-2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl)-(l-4)-O-(2,3-di-O-methy1-β-D-glucopyranosyluronic acid)-(l-4)-O-(2,3,6-tri-O-

sulpho-α-D-glucopyranosyl)-(1-4)-(2,3-di-O-methyl-α-L-idopyranosyluronic acid)-(1-4)-2,3,6-tri-O-sulpho-α-D-glucopyranoside, sodium salt
o Methyl 0-(3-O-methyl-2,4,6-tri-O-sulpho-α-D-glucopyranosyl) - (1-4) -O- ( 3-O-methyl-2 , 6-di-O-sulpho-(3-D-glucopyranosyl)-(l-4)-[0-(2,3,6-tri-O-methyl-α-D-glucopyranosyl)-(l-4)-O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl)-(l-4)]4-O-2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl) -(l-4)-O-(2,3-di-O-methyl-β-D-glucopyranosyluronic acid)-(1-4)-O-(2,3,6-tri-Q-sulpho-a-D-glucopyranosyl) -(1-4)-(2,3-di-O-methyl-α-L-idopyranosyluronic acid)-(1-4)-2,3,6-tri-O-sulpho-α-D-glucopyranoside, sodium salt
o Methyl 0-(3-O-methyl-2,4,6-tri-O-sulpho-α-D-glucopyranosyl) - (1-4)-O-(3-O-methyl-2,6-di-O-sulpho-β-D-glucopyranosyl)-(l-4)-[0-(2,3,6-tri-O-methyl-α-D-glucopyranosyl)-(l-4)-O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl)-(l-4)]5-O-2,3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl)-(l-4)-O-(2,3-di-O-methyl-β-D-glucopyranosyluronic acid)-(1-4) -O-(2,3,6-tri-O-sulpho-a-D-glucopyranosyl)-(1-4)-(2,3-di-O-methyl-α-L-idopyranosyluronic acid)-(1-4) -2,3,6-tri-O-sulpho-α-D-glucopyranoside, sodium salt.
10. Process for the preparation of the compounds of formula (I) , wherein, in a first step, a fully protected precursor of the desired polysaccharide (I) , containing a protected precursor of the Pe region elongated at its non-reducing end by a protected precursor of the sulphated polysaccharide Po, is synthesized and, in a second step, the negatively-enlarged groups are then introduced and/or demasked. 11. Compound of formula


in which T1 and Tn, which may be identical or different, represent a temporary, semi-permanent or permanent substituent, and Z is a protecting group for a hydroxyl function.
12. Compound of formula:

in which T1 and Tn, which may be identical or different, represent a temporary, semi-permanent or permanent substituent, Z is a protecting group for a hydroxyl function.
13. Pharmaceutical compositions containing, as active principle, a polysaccharide or salt according to any one of Claims l to 9, in the form of a salt with a pharmaceutically acceptable base or in acid form, in combination or as a mixture with an inert, non-toxic, pharmaceutically acceptable excipient,
14. Pharmaceutical composition according to Claim 13, in the form of dosage units, in which the active principle is mixed with at least one pharmaceutical excipient.
15. Composition according to Claim 14, in which each dosage unit contains from 0.1 to 100 mg of active principle.
16. Composition according to Claim 15, in which each dosage unit contains from 0.5 to 50 mg of active principle.

Dated this 14 day of July 1997



Heparin belongs to the family of glycosaminoglycans (GAGs), which are heterogeneous natural sulphated polysaccharides.
Heparin preparations are mixtures of chains comprising a number of monosaccharide units ranging from 10 to 100 and more. In addition to this size heterogeneity there is a structural heterogeneity, as regards the nature of the constituent monosaccharides and also as regards the substituents which they bear (L. Roden in: The Biochemistry of Glycoproteins and Glycosaminoglycans, Ed by Lennarz W.J,, Plenum Press, New York and London, 267-371, 1980).
Each family of natural GAGs generally possesses a wide range of pharmacological activities. All are combined in the preparations which may be obtained from natural products. Thus, for example, the heparin and heparan sulphates possess an antithrombotic activity which is associated with the simultaneous action of several coagulation factors.
Heparin catalyses, in particular via antithrombin III (AT III), the inhibition of two enzymes involved in the blood coagulation cascade, namely factor Xa and factor IIa (or thrombin) . Low molecular weight heparin (LMWH) preparations contain chains formed of 4 to 3 0 monosaccharides and have the property of acting more selectively on factor Xa than on thrombin.
Certain synthetic oligosaccharides, in particular those described in EP 84,999, have the property of selectively inhibiting, via antithrombin III, factor Xa without having any activity on thrombin.
It is known that the inhibition of factor Xa requires binding of the heparin to AT III via the antithrombin-binding region (ABR), and that the

inhibition of factor Ila (thrombin) requires binding to AT (III) , via ABR, as well as to thrombin via a less well-defined binding region (TBR).
The synthetic oligosaccharides corresponding to the ABR region of heparin are known and manifest an antithrombotic activity in venous thrombosis. These compounds are described in EP 529,715 and EP 621,282 and in Canadian patent 2,040,905.
The efficacy of these oligosaccharides in the prevention of arterial thrombosis is, nevertheless, hampered by their inability to inhibit thrombin.
A synthesis of glycoaminoglycans of heparin type which are capable of inhibiting thrombin via the AT (III) activator presents great difficulties and, indeed, this has never been achieved.
With the aim of rediscovering the activity of thrombin-inhibitor and factor Xa-inhibitor products, in EP-A-0,649,854 it has been proposed to connect two small oligosaccharides (an ABR and a TBR) by a species {'spacer") which is not involved in the biological activity.
It has now been found that novel polysaccharide derivatives may be synthesized relatively simply and are biologically active. They are, in particular, anticoagulant and antithrombotic. Furthermore, on account of the production of these polysaccharides by synthesis, it is possible to selectively modify their structure, and in particular to remove unwanted sulphate substituents involved in the interaction with certain proteins. Thus, polysaccharides may be obtained which are powerful antithrombotic and anticoagulant agents and which may furthermore escape in vivo the action of proteins such as platelet factor 4 (PF4), which neutralize the effect of heparin in particular on thrombin.
Thus, it has been found, surprisingly, that sulphated and alkylated polysaccharides may be powerful antithrombotic and anticoagulant agents depending on

the arrangement of the alkyl and sulphate groups borne by. the carbohydrate skeleton.
More generally, it has been found that by preparing polysaccharide sequences, it is possible to modify with precision the GAG-type activities in order to obtain very active products which have the properties of heparin.
Thus, according to one of its aspects, the present invention relates to a novel synthetic polysaccharide comprising an antithrombin III-binding region consisting of a sequence of five monosaccharides bearing in total two carboxylic acid functions and at least four sulphate groups, this region being extended at its non-reducing end by a thrombin-binding region comprising a sequence of 10 to 25 monosaccharide units chosen from hexoses, pentoses or deoxy sugars in which al 1 the hydroxy1 groups are, independently, etherified with a (C1-C6) alkyl group or esterified in the form of sulphate groups, as well as its salts, in particular its pharmaceutically acceptable salts•
Preferably, the invention relates to a polysaccharide as defined above, characterized in that all its hydroxyl groups are etherified with a methyl or are esterified in the form of a sulpho group and its salts, in particular its pharmaceutically acceptable salts.
The products of the present invention are, in particular, polysaccharides represented by the following formula:

in which
- the wavy line denotes a bond either below or above the plane of the pyranose ring,


denotes a polysacchaR1de Po containing n identical or different monosacchaR1de units, which is linked via its anomeR1c carbon to Pe,

is a diagrammatic representation o£ a monosacchaR1de unit of pyranose structure chosen from hexoses, pentoses and the corresponding deoxy sugars, this unit being linked via its anomeR1c carbon to another monosacchaR1de unit, and the hydroxyl groups of this unit being substituted with identical or different groups -*X, the groups X being chosen from (Gi.Ci)alkyl groups and sulpho groups,
- n is an integer from 10 to 25,
- Pe represents a group,acchaR1de of structure:

in which
- R1 represents a (C1-C6)alkyl or a sulpho group,
- R1a represents R1 or constitutes, with the oxygen atom to which it is attached and the carbon atom beaR1ng the carboxylic :function on the same R1ng, a group
C-CH2-O,
- R represents a (C1-C6)alkyl,
- W represents an oxygen atom or a methylene group,
or one of their salts, in particular a salt which is pharmaceutically acceptable.

It will be noted in general in the present descR1ption that a wavy line denotes a bond either below or above the plane of the pyranose R1ng.
The monosaccharides contained in Po may be identical to or different from each other, and the interglycoside linkages may be of the a or β type.
These monosaccharides are advantageously chosen from the D or L hexoses allose, altrose, glucose, mannose, galose, idose, galactose and talose (in this case h=3) or from the D or L pentoses R1bose, arabinose, xylose and lyxose (in this case h=2) . Other monosaccharides such as, for example, deoxy sugars may also be used (h = 1 and/or -CH2OX = CH3) .
When, in the pentasaccharides Pe, the unit W represents an oxygen atom and R1a is as defined for R1, these pentasaccharides constitute known compounds descR1bed in particular in patents EP 300,099, EP 529,715, EP 621,282 and EP 649,854 as well as in the literature. They are obtained from synthons which are also descR1bed in the literature by C. van Boeckel and M. Petitou, Angew. Chem. Int. Ed• Engl., 1993, 32, 1671-1690.
When, in the pentasaccharides Pe, Rxa is other than R1 and/or W represents a carbon atom, these pentasaccharides are prepared using novel synthons which constitute a further aspect of the invention.
When, in the pentasaccharides Pe, the unit of L-iduronic acid type is replaced with a unit whose conformation is locked by a bR1dge, these pentasaccharides are prepared using novel synthons which constitute a further aspect of the invention.
Thus, according to another of its aspects, the present invention relates to novel intermediates which are useful for the preparation of compounds (I).
The polysaccharide part Po may consist of 10 to 25 al ylated and di- or tR1sulphated monosaccharide units.

The polysaccharide 'part Po may consist of 10 to 2 5 alkylated and mono- or disulphated monosaccharide units.
The polysaccharide part Po may consist of 10 to 25 uncharged and/or partially charged and/or fully charged alkylated monosaccharide units.
The charged or uncharged units may be dispersed along the entire length of the chain or they may, in contrast, be grouped in charged or uncharged saccharide regions.
The linkages may be 1,2; 1,3; 1,4; 1,5; 1,6; and of the a or p type.
In the present descR1ption, it has been chosen to represent the conformations 1C4 for L-iduronic acid and 4C1 for D-glucuronic acid, but it is well known that, in general, the conformation of the monosaccharide units in solution fluctuates. Thus, L-iduronic acid may be of 104 2So or 1C1 conformation.
Preferred compounds according to the invention are those of formula (I.A):

denotes a particular family of polysaccharides Po, linked via their anomeR1c carbon to Pe as defined for (I) ,


is as defined for (I),
- the OXs are as defined for (I) and, for the same
polysaccharide, may be identical or different,
the monosaccharides contained in []m form a disaccharide repeated m times, the monosaccharides contained in []t form a disaccharide repeated t times,
- m ranges from 1 to 8, t ranges from 0 to 5 and p
ranges from 0 to 1, it being understood that
5 and their salts, in particular their pharmaceutically acceptable salts.
Advantageous compounds are the salts whose anion corresponds to formula (I.l):

in which t represents 5, 6 or 7, and the cation is a pharmaceutically acceptable monovalent cation, as well as the corresponding acids.
The salts whose anion corresponds to formula (1.2) :

in which t represents 5, 6 or 7, and the cation is a pharmaceutically acceptable monovalent cation, as well as the corresponding acids, are also advantageous.

The salts whose anion has the formula (1.3):

in which m represents 1, 2 or 3 and t represents 2, 3, 4 or 5, and the cation is a pharmaceutically acceptable monovalent cation, as well as the corresponding acids, are particularly advantageous.
Other preferred compounds according to the invention are those of formula (II.A):

denotes a specific family of polysaccharides Po, linked via their anomeR1c carbon to Pe as defined for (I),

is as defined for (I),

- the groups OX are as defined for (I) and, for the same monosaccharide, may be identical or different,
- the monosaccharide contained in []m' is repeated m' times, the monosaccharide contained in []' is repeated t' times, t' ranges from 0 to 24 and p' ranges from 0 to 24, it being understood that 10 and the pharmaceutically acceptable salts thereof.
The preferred salts of the invention are those chosen from alkali metal cations and even more preferably those in which the cation is Na" or K*.
The following polysaccharides are particularly preferred:
• Methyl O-(3-O-methyl-2,4,6-tR1-O-sulpho-α-D-glucopyranosyl) - (l->4) -O- (3"O-methyl-2, 6-di-O-sulpho-β-D-glucopyranosyl) - (l->4) - [O- (3-0"methyl-2, 6-di-O-sulpho-a-D-glucopyranosyl) - (l-»4) -O- (3-O-methyl-2, 6-di-O-sulpho-β-D-glucopyranosyl) - (l->4) ]4-O- (2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl)-(l->4) -O-(2 , 3-di-O-methyl-(3-D-glucopyranosyluronic acid) - (1—4) -O- (2,3,6-tR1-O-sulpho-α-D-glucopyranosyl)-(l->4) -O-(2,3-di-O-methyl-α-L-idopyranosyluronic acid) - (1-4)-2,3,6-tR1-O-sulpho-α-D-glucopyranoside, sodium salt
• Methyl O-(3-0"methyl-2,4,6-tR1-O-sulpho-α-D-glucopyranosyl) - (l->4) -O- {3-O-methyl-2, 6"di-O-sulpho-β-D-glucopyranosyl) - (1->4) -[O- (3-O-methyl-2; 6-di-O-sulpho-a-D-glucopyranosyl)-(1,4)-O-(3-O-methyl-2,6-di-O-sulpho-3-D-glucopyranosyl) - (l->4) ]s-O- (2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl)-(l->4) -O-(2, 3-di-O-methyl-β-D-glucopyranosyluronic acid)-(1,4)-O-(2,3,6-tR1-O-sulpho-α-D-glucopyranosyl)- (1→4) -O-(2,3-di-O-methyl-α-L-idopyranosyluronic acid)-(1→4) -2,3, 6-tR1-O-sulpho-α-D-glucopyranoside, sodium salt
• Methyl O-(3-O-methyl-2,4,6-tR1-O-sulpho-α-D-glucopyranosyl) - (l->4) -O- (3-O-methyl-2, 6-di-O-sulpho-β-D-glucopyranosyl) - (1→4) - [O- (3-O-methyl-2, 6-di-O-sulpho-α-D-glucopyranosyl) - (1→4) -O- (3-O-methyl-2 , 6-di-O-sulpho-β-D-glucopyranosyl) - (1→4) ] g-O- (2 , 3-di-O-methyl-6-O-sulpho--D-glucopyranosyl) - (1→4) -O- (2, 3-di-O-methyl-β-D-glucopyranosyluronic acid)- (1→4)-O-(2,3,6-

tR1-O-sulpho-α-D-glucopyranbsyl)- (l→4) -O-(2, 3-di-O-methyl-α-L-idopyranosyluronic acid)- (l->4) -2, 3, 6-tR1-O-sulpho-α-D-glucopyranoside, sodium salt
• Methyl O-(2,3-di-O-methyl-4,6-di-O-sulpho-α-D-glucopyranosyl) - (l->4) - [O- (2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl)-(1-^4) -] n-O-(2,3-di-O-methyl-β-D-glucopyranosyluronic acid) -(1, 4) -O-(2, 3, 6-tR1-O-sulpho-α-D-glucopyranosyl)- (1-^4 ) -O-(2, 3-di-O-methyl-α-L-idopyranosyluronic acid) - (l→4) -2,3; 6-tR1-O-sulpho-α-D-glucopyranoside, sodium salt
• Methyl O-(2, 3-di-O-methyl-4,6-di-O-sulpho-α-D-glucopyranosyl) - (1^4) - [O- (2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl)-(l→4) -] 13-O-(2,3-di-O-methyl-β-D-glucopyranosyluronic acid) - (1-^4) -O-(2, 3, 6-tR1-O-sulpho-α-D-glucopyranosyl)- (1^4) -O-(2, 3-di-O-methyl-α-L-idopyranosyluronic acid)- (l→4) -2,3, 6-tR1-O-sulpho-α-D-glucopyranoside, sodium salt
• Methyl O-(2, 3-di-O-methyl-4,6-di-O-sulpho-α-D-glucopyranosyl) - (l->4) - [O- (2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl) - (1→4) -] 15-O- (2, 3-di-O-methyl-3-D-glucopyranosyluronic acid) - (l->4)-O-(2, 3, 6-tR1-O-sulpho-α-D-glucopyranosyl)- (l->4) -O-(2, 3-di-O-methyl-α-L-idopyranosyluronic acid)- (l->4) -2,3, 6-tR1-O-sulpho-α-D-glucopyranoside, sodium salt
• Methyl O-(3-O-methyl-2,4,6-tR1-O-sulpho-α-D-glucopyranosyl) - (1^4) -O- (3-O-methyl-2, 6-di-O-sulpho-(3-D-glucopyranosyl) - (l→4) - [O- (3-O-methyl-2, 6-di-O-sulpho-α-D-glucopyranosyl) - (1-^4) -O- (3-O-methyl-2, 6-di-O-sulpho-β-D-glucopyranosyl) - (1^4) ] 2- [O- (2, 3, 6-tR1-O-methyl-α-D-glucopyranosyl) - (l→4) -O- (2,3, 6-tR1-O-methyl-p-D-glucopyranosyl) - (l->4) ] 2-O-2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl) - (1^4) -O- (2, 3-di-O-methyl-β-D-glucopyranosyluronic acid) - (l→4) -O-(2,3,6-tR1-O-sulpho-α-D-glucopyranosyl) - (1→4) - (2, 3-di-O-methyl-α-L-idopyranosyluronic acid) - (l→4) -2, 3, 6-tR1-O-sulpho-α-D-glucopyranoside, sodium salt
• Methyl O-(3-O-methyl-2, 4, 6-tR1-O-sulpho-α-D-glucopyranosyl) - (l->4) -O- (3-O-methyl-2, e-di-O-sulpho-β-D-glucopyranosyl)- (1-^4) -[O-(3-O-methyl-2, 6-di-O-sulpho-

^ α-D-glucopyranosyl)- (1->4) -O-(3-O-methyl-2,6-di-O-sulpho-β-D-glucopyranosyl)-(1^4) ] — [O-(2,3,6-tR1-O-methyl-α-D-glucopyranosyl)- (1^4) -O-(2, 3, 6-tR1-O-methyl-p-D-glucopyranosyl) - (1->4) ] 3-O-2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl)- (l->4) -O-(2, 3-di-O-methyl-3-D-glucopyranosyluronic acid) - (l->4) -O-(2, 3,6-tR1-O-sulpho-α-D-glucopyranosyl) - (1->4) -(2, 3-di-O-methyl-α-L-idopyranosyluronic acid) - (1-^4) -2,3, 6-tR1-O-sulpho-α-D-glucopyranoside, sodium salt
• Methyl O-(3-O-methyl-2,4,6-tR1-O-sulpho-α-D-glucopyranosyl)- (1^4) -O-(3-O-methyl-2, 6-di-O-sulpho-β-D-glucopyranosyl) - (l->4) -O- (3-O-methyl-2, 6-di-O-sulpho-α-D-glucopyranosyl)- (l->4) -O-(3-O-methyl-2,6-di-O-sulpho-β-D-glucopyranosyl)-(l->4) - [O- (2, 3, 6-tR1-O-methyl-α-D-glucopyranosyl)- (1^4) -O-(2, 3, 6-tR1-O-methyl-p-D-glucopyranosyl) - (1^4) ] 4-O-2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl) - (1^-4) -O- [2, 3-di-O-methyl-β-D-glucopyranosyluronic acid) - (1^4) -O-(2, 3, 6-tR1-O-sulpho-α-D-glucopyranosyl)- (l->4) -[2, 3-di-O-methyl-α-L-idopyranosyluronic acid)- (1->4) -2, 3, 6-tR1-O-sulpho-α-D-glucopyranoside, sodium salt
• Methyl O-(3-O-methyl-2,4,6-tR1-O-sulpho-α-D-glucopyranosyl)- (l->4) -O-(3-O-methyl-2, 6-di-O-sulpho-β-D-glucopyranosyl) - (l->4) -O- (3-O-methyl-2, 6-di-O-sulpho-α-D-glucopyranosyl)- (l->4) -O-(3-O-methyl-2,6-di-O-sulpho-β-D-glucopyranosyl)- (l->4) -[O-(2, 3, 6-tR1-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2, 3, 6-tR1-O-methyl-P-D-glucopyranosyl) - (1^4) ] 3-O-2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl) - (l->4) -O- [2, 3-di-O-methyl-β-D-glucopyranosyluronic acid)- (l->4) -O-{2, 3, 6-tR1-O-sulpho-α-D-glucopyranosyl)- (l->4) -(2, 3-di-O-methyl-α-L-idopyranosyluronic acid) - (l-»4)-2,3, 6-tR1-O-sulpho-α-D-glucopyranoside, sodium salt
• Methyl O-(3-O-methyl-2,4,6-tR1-O-sulpho-α-D-glucopyranosyl) - (l->4) -O- (3-O-methyl-2, 6-di-O-sulpho-β-D-glucopyranosyl)- (l->4) -[O-(2, 3, 6-tR1-O-methyl-α-D-glucopyranosyl) - (l->4)-O-{2, 3,6-tR1-O-methyl-β-D-glucopyranosyl) - (1^4) ]4-O-2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl)- (l->4) -O-(2, 3-di-O-methyl-β-D-

glucopyranosyluronic acid) - (1^4) -O-(2, 3, 6-tR1-O-sulpho-α-D-glucopyranosyl)- (1-^4 ) -(2, 3-di-O-methyl-α-L-idopyranosyluronic acid)-(l->4) -2,3, 6-tR1-O-sulpho-α-D-glucopyranoside/ sodium salt
• Methyl O- (3-O-inethyl-2, 4, 6-tR1-O-sulpho-α-D-glucopyranosyl) - (l->4) -O- (3-O-methyl-2, 6-di-O-sulpho-β-D-glucopyranosyl)- (1-^4) -[O-(2, 3, 6-tR1-O-methyl-α-D-glucopyranosyl)- (l->4) -O-(2, 3, e-tR1-O-methyl-β-D-glucopyranosyl) - (l->4) ] 5-O-2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl)- (l->4) -O-{2, 3-di-O-methyl-β-D-glucopyranosyluronic acid) - (l->4) -O-(2, 3, 6-tR1-O-sulpho-α-D-glucopyranosyl)- (1">4) -(2, 3-di-O-methyl-α-L-idopyranosyluronic acid) - (l-»4) -2, 3, 6-tR1-O-sulpho-α-D-glucopyranoside, sodium salt.
The present invention relates to a process for the preparation of the compounds of formula (I) , wherein, in a first step, a fully protected precursor of the desired polysaccharide (I) , containing a protected precursor of the Pe region (this region being shown in Scheme 1) elongated at its non-reducing end by a protected precursor of the sulphated polysaccharide Po, is synthesized and, in a second step, the negatively-charged groups are then introduced and/or demasked.

In a first approach, the fully protected precursor of the tetrasaccharide part EFGH of the pentasaccharide may be used. A polysaccharide Po which contains at its reducing-terminal end the missing unit

D of Pe is then added in order to obtain, after coupling, the entire ABR which is thus restored.
In another approach, the fully protected precursor of the disaccharide part GH of the pentasaccharide may be used. A polysaccharide Po precursor of the TBR which contains at its reducing-terminal end the missing unit DEF of Pe is then added in order to obtain, after coupling, the entire ABR which is thus restored.
These Pe precursors are synthesized as indicated above from synthons descR1bed in the literature or forming part of the present invention.
The polysaccharide precursor part of Po is synthesized according to reactions which are well known to those skilled in the art, using the methods for synthesizing oligosaccharides (G.J. Boons, Tetrahedron, 1996, 52, 1095-1121) or an oligosaccharide when a glycosidic-linkage-donating oligosaccharide is coupled with a glycosidic-linkage-accepting oligosaccharide in order to lead to another oligosaccharide whose size is equal to the sum of the sizes of the two reactive species.
This sequence is repeated until the desired compound of formula (I) is obtained. The nature and profile of the charge of the desired final compound determine the nature of the chemical species used in the vaR1ous steps of the synthesis, according to rules which are well known to those skilled in the art.
A preferred method for the preparation of the Po precursors according to the present invention is shown in Scheme 2 below:


The term temporary is understood to refer to a substituent which is conserved for a limited number of steps, the term semi-permanent is understood to refer to a substituent which is conserved for a larger number of steps, and the term permanent is understood to refer to a substituent which is conserved to the end of the synthes is; the permanent substituents are removed duR1ng the final step. Certain permanent groups may form part of the final molecule.
In Scheme 2, (a) represents a glycosidic-linkage-donor monosaccharide in which Z is a temporairy protecting group of a hydroxyl function and Y is an anomeR1c-carbon activator, Tn, which may be identical or different, are temporary, semi-permanent or permanent substituents of all the other hydroxyl functions.

The compound (b) which possesses an unsubstituted hydroxy1 group represents a glycosidic-linkage-acceptor monosaccharide in which Tn, which may be identical or different, are temporary, semipermanent or permanent substituents of the hydroxyl groups. T1 is a temporary, semi-permanent or permanent protecting group of the anomeR1c position. It is removed when it is desired to activate .the anomeR1c carbon.
With the aim of obtaining the compounds of the invention, the glycosidic-linkage donor (a) and the glycosidic-linkage acceptor (b) react together to give the disaccharide (c).
The disaccharide (c) obtained above is converted specifically into a glycosidic-linkage-donor disaccharide (d) by removal of T1 and introduction of Y and/or into a glycosidic-linkage acceptor (e) by removal of Z.
Next, the glycosidic-linkage donor (d) and the glycosidic-linkage acceptor (e) react together to give the tetrasaccharide (f) in which t represents 1.
Repetition of this sequence of reactions gives an oligo- or a polysaccharide (f) in which t is greater than 1.
It is also possible, using the process represented in Scheme 2, to obtain a large vaR1ety of fully protected oligo- or polysaccharides such as (g) in which the oligosaccharides [ ] m and [ ] t are fully protected precursors of differently charged regions of the compounds of the invention.
In the following step of the process, the compounds such as (f) and (g) are converted into glycosidic-linkage donors and are coupled to the non-reducing terminal unit of fully protected precursors of Pe.
As has been mentioned above, the oligosaccharide of the non-reducing terminal unit of a glycosidic-linkage-donor polysaccharide (g) may constitute a part of Pe, in the case where (g) is

coupled to the non-reducing terminal unit of a fully protected oligosaccharide which is the precursor of the residue of the structure of Pe.
The compounds of the invention are obtained from their fully protected polysaccharide precursors using the following sequence of reactions:
- the alcohol functions which need to be converted into a sulpho group and the carboxylic acids are deprotected by removal of the Tn groups used to protect them duR1ng the development of the skeleton, then
- the sulpho groups are subsequently introduced.
The compounds of the invention may, naturally, be prepared using vaR1ous strategies known to those skilled in the art of oligosaccharide synthesis.
The process descR1bed above is the preferred process of the invention. However, the compounds of formula (I) may be prepared by other well-known methods of sugar chemistry descR1bed, for example, in Monosaccharides, Their chemistry and their roles in natural products, P.M. Collins and R.J. FerR1er, J. Wiley Sc sons, 1995 and in G.J. Boons, Tetrahedron, 1996, 52, 1095-1121.
The precursor of the part of the pentasaccharide Pe when W represents an oxygen atom and R1a is R1 is prepared according to oligosaccharide synthesis methods and particularly according to the methods descR1bed in patents EP 84,999, EP 3 01,618, EP 454,220 and EP 529,715 and in patent applications EP 93204769 and EP 94202470. When complete protection is carR1ed out, it is possible, using suitable protecting groups, to obtain a free hydroxyl group on position 4 of the non-reducing terminal unit (D) . The fully protected precursor of Pe is then coupled to this position using the known methods of oligosaccharide synthesis.
The pentasaccharide Pe in which W represents a carbon atom and R1a is R1, of formula:


in which T1 and Tn,, which may be identical or different, represent a temporary, semi-permanent or permanent substituent, Z is a protecting group for a hydroxyl function which is itself obtained by a synthesis carR1ed out by means of a radical reaction between a free-radical-generating monosaccharide and a monosaccharide containing a double bond, the C-disaccharide thus obtained then being converted into synthon (II.1) according to the standard methods descR1bed above according to C. van Boeckel and M. Petitou.
The synthon of formula (II. 1) , which is particularly useful in the synthesis of the compounds (II), is of formula:

(II.l) or compound 90 This synthon is prepared according to the reaction scheme descR1bed in Scheme 22 below.

The pentasaccharide Pe which features a substituent R1a which constitutes an L-iduronic acid unit of locked configuration, of formula:

in which R and R1 are as defined for (I) and W represents an oxygen atom, are obtained from the synthon of formula:

in which T1 and Tn, which may be identical or different, represent a temporary, semi-permanent or permanent substituent, Z is a protecting group for a hydroxyl function which is itself obtained by a synthesis carR1ed out according to the methods descR1bed in the literature M.K. Gurjar et al., Tetrahedron letters, 1995, 36, 11, 1937-194 0, 1933-1936 and 1994, 35, 14, 2241-2244.
The synthon of formula (III. 1) which is particularly useful for synthesizing the compounds (III) is of formula:

This synthon is prepared according to the reaction scheme descR1bed in Scheme 34 below.

The intermediates '(II.l) and (III.l) are novel intermediates which are particularly useful for prepaR1ng the compounds (I) according to the invention.
The pentasaccharides Pe may thus be obtained from these disaccharide synthons (II.1) or (III.l) in the way descR1bed in the publication by C.A.A. van Boeckel and M. Petitou, Angew. Chem. Int. Ed, Engl. mentioned above.
The term semi-permanent groups used above is understood to refer to the groups which can be removed firstly after the glycosylation reactions when the carbohydrate skeleton contains the desired number of units, without removing or adversely affecting the other groups present, thereby allowing the introduction of desired functional groups into the positions they occupy.
The permanent groups are groups capable of maintaining the protection of the OH functions duR1ng introduction of the functional groups in place of the semi-permanent groups.
These groups are chosen from those which are compatible with the functional groups introduced after removal of the semi-permanent groups. They are, moreover, groups which are inert towards the reactions carR1ed out to install these functional groups and which may be removed without these functional groups being adversely affected.
According to the invention, the permanent groups are preferably (C1-C6)alkyl groups.
Examples of semi-permanent and/or temporary groups which may be mentioned are benzyl and acetyl, levulinyl, p-methoxybenzyl groups, etc,.
The substituents in position 3 of the uronic units of the target compound may already be present in the starting synthons, along with the substituent R1.
The protecting groups used in the process for prepaR1ng the compounds (I) are those commonly used in sugar chemistry, for example in Protective Groups in

Organic Synthesis, TW Greene, John Wiley & sons, New York, 1981.
The protecting groups are advantageously chosen, for example, from acetyl, halomethyl, benzoyl, levulinyl, benzyl, substituted benzyl, optionally substituted tR1tyl, tetrahydropyranyl, allyl, pentenyl, tert-butyldimethylsilyl (tBDMS) or tR1methylsilylethyl groups (etc.).
The activating groups are those conventionally used in sugar chemistry, for example according to G.J. Boons, Tetrahedron, 1996, 52, 1095-1121, These activating groups are chosen, for example, from imidates, thioglycosides, pentenylglycosides, xanthates, phosphites and halides.
The process descR1bed above makes it possible to obtain the compounds of the invention in the form of salts• In order to obtain the corresponding acids, the compounds of the invention in the form of salts are placed in contact with a cation-exchange resin in acidic form.
The compounds of the invention in acidic form may then be neutralized with a base in order to obtain a desired salt-
For the preparation of the salts of the compounds of formula (I), any organic or inorganic base may be used, giving, with the compounds of formula (I), pharmaceutically acceptable salts.
Sodium hydroxide, potassium hydroxide, calcium hydroxide or magnesium hydroxide is preferably used as ■ base. The sodium and calcium salts of the compounds of formula (I) are the preferred salts.
In step (a) of the process, the protecting groups used are those usually used by those skilled in the art of sugar chemistry, for example according to EP 84,999 or alternatively according to Protective Groups in Organic Synthesis, TW Greene, J, Wiley & sons, 1995.
The compounds (I) thus obtained may optionally be salifled.

The compounds of formula (I) above also compR1se those in which one or more hydrogen or carbon atoms have been replaced with their radioactive isotope, for example tR1tium or carbon-14. Such labelled compounds are useful in pharmacokinetic, metabolism or research studies, and in biochemical tests as ligands.
The compounds according to the invention formed the subject of biochemical and pharmacological studies which showed that they possess very advantageous properties.
The compounds of the present invention which bind selectively to AT III with an affinity equal to or greater than that of hepaR1n possess the anticoagulant and antithrombotic properties of hepaR1n.
The overall antithrombotic activity of the products of formula (I) was evaluated intravenously or subcutaneously in rats, in a model of venous stasis and induction by thromboplastin, according to the method descR1bed by J. Reyers et al. in Thrombosis Research, 1980, 18, 669-674 as well as in a model of arteR1al thrombosis consisting of a shunt implanted between the carotid artery and the jugular vein of rats, as descR1bed by Umetsu et al. Thromb. Haemost., 1978, 39, 74-83. In these two expeR1mental models, the ED50 of the compounds of the invention is at least of the same order as or less than that of the other synthetic hepaR1noids already known (ED50 between 5 and 500 (ig/kg) . The compounds of the invention thus have a
specificity of action and an anticoagulant and antithrombotic activity which are particularly advantageous.
By virtue of their biochemical and pharmaceutical activity, the compounds of the present invention are very advantageous medicines. Their toxicity is entirely compatible with this use. They are also very stable and are thus particularly suitable for constituting the active pR1nciple of pharmaceutical specialty products.

Furthermore, the dompounds of the invention are not neutralized by large doses of cationic platelet proteins such as platelet factor 4 (PF4) released duR1ng activation of these proteins in the process of thrombosis. The compounds of the invention are thus particularly advantageous for the treatment and prevention of thrombosis of arteR1al or venous oR1gin.
They may be used in vaR1ous pathologies which are consecutive to a modification of the haemostasis of the coagulation system, which appears in particular duR1ng disorders of the cardiovascular and cerebrovascular system, for instance thromboembolic disorders associated with atherosclerosis and with diabetes, such as unstable angina, cerebral attacks, restenosis after angioplasty, endarterectomy and the installation of endovascular prostheses; or thromboembolic disorders associated with rethrombosis after thrombolysis, with infarction, with dementia of Lschaemic oR1gin, with peR1pheral arteR1al diseases, with haemodialysis and with auR1cular fibR1llations or alternatively duR1ng the use of vascular prostheses of aortocoronary bR1dges. These products may moreover be used for the treatment or prevention of thromboembolic pathologies of venous oR1gin such as pulmonary embolism. They may be used for preventing or treating thrombotic complications which appear duR1ng surgical interventions or together with other pathologies such as cancer and bacteR1al or viral infections. When they are used duR1ng the installation of prostheses, the compounds of the present invention may coat the prostheses and thus make them haemocompatible. In particular, they may be bound to intravascular prostheses (stents). In this case, they may optionally be chemically modified by introduction of a suitable arm onto the reducing or non-reducing end, as descR1bed in EP 649,854.
The compounds of the present invention may also be used as adjuvants duR1ng endarterectomy performed with small porous balloons.

The compounds of the invention are very stable and are thus particularly suitable for constituting the active pR1nciple of medicines.
According to another of its aspects, the subject of the present invention is thus a pharmaceutical composition containing, as active pR1nciple, a synthetic polysaccharide as defined above.
The invention preferably relates to pharmaceutical compositions containing, as active pR1nciple, a compound of formula (I) , (1.1), (1.2) or (1.3) or one of its pharmaceutically acceptable salts, optionally in combination with one or more inert and suitable excipients.
In each dosage unit, the active pR1nciple is present in amounts adapted to the daily doses envisaged. In general, each dosage unit is conveniently adjusted according to the dosage and type of administration planned, for example tablets, gelatin capsules and the like, sachets, ampules, syrups and the like, drops and transdermal or transmucous patches, such that one dosage unit contains from 0.1 to 100 mg of active pR1nciple, preferably 0,5 to 50 mg.
The compounds according to the invention may also be used in combination with another active pR1nciple which is useful for the desired therapy such as, for example, antithrombotic agents, anticoagulants or platelet-antiaggregating agents, for example such as dipyR1damole, aspiR1n, ticlopidine, clopidogrel or antagonists of the glycoprotein Ilb/IIIa complex.
The pharmaceutical compositions are formulated for administration into mammals, including man, for the treatment of the abovementioned diseases.
The pharmaceutical compositions thus obtained are advantageously in vaR1ous forms such as, for example, injectable or dR1nkable solutions, tablets, coated tablets or gelatin capsules. The injectable solutions are the preferred pharmaceutical forms. The pharmaceutical compositions of the present invention are useful in particular for the preventive or curative

treatment of disorders of/the vascular wall, _ such_ as atherosclerosis, the hypercoagulability states observed, for example, after surgical .operations, tumour development or deregulation of coagulation, which are induced by bacteR1al, viral or enzymatic activators. The dosage may vary widely as a function of the age, weight and state of health of the patient, the nature and seveR1ty of the complaint and the route of administration. This dosage compR1ses the administration of one or more doses of from 0.1 mg to 100 mg per day approximately, preferably from 0.5 to 5 0 mg per day approximately, intramuscularly or subcutaneously, in continuous administrations or administrations at regular intervals.
The subject of the present invention is thus also pharmaceutical compositions which contain, as active pR1nciple, one of the above compounds optionally combined with another active pR1nciple. These compositions are prepared so as to be able to be administered via the digestive or parenteral route.
In the pharmaceutical compositions of the present invention for oral, sublingual, subcutaneous, intramuscular, intravenous, transdermal, transmucous, local or rectal administration, the active ingredient ■nay be administered in unit forms of administration, nixed with standard pharmaceutical vehicles, to animals and to man. The appropR1ate unit forms of administration compR1se oral forms such as tablets, jelatin capsules, powders, granules and oral suspensions or solutions, sublingual and buccal administration forms, subcutaneous, intramuscular. Intravenous, intranasal or intraoccular administration forms and rectal administration forms.
When a solid composition in tablet form is prepared, the main active ingredient is mixed with a Pharmaceutical vehicle such as gelatin, starch, Lactose, magnesium stearate, talc, gum arable or the -ike. The tablets may be coated with sucrose or other suitable mateR1als or alternatively they may be treated

such that they have a sustained or delayed activity and so that they release a predetermined amount of active pR1nciple continuously.
A preparation in gelatin capsules is obtained by mixing the active ingredient with a diluent and pouR1ng the mixture obtained into soft or hard gelatin capsules,
The water -dispersible powders or granules may contain the active ingredient mixed with dispersing agents or wetting agents, or suspending agents, for instance polyvinylpyrrolidone, as well as with sweeteners or flavour enhancers.
For rectal administration, use is made of suppositoR1es which are prepared with binders that melt at rectal temperature, for example cocoa butter or polyethylene glycols.
For parenteral, intranasal or intraoccular administration, steR1le, injectable solutions, isotonic saline solutions or aqueous suspensions which contain pharmacologically compatible dispersing agents and/or wetting agents, for example propylene glycol or butylene glycol, are used.
For transmucous administration, the active
pR1nciple may be formulated in the presence of a
promoter such as a bile salt or in the presence of a
hydrophilic polymer such as, for example,
hydroxypropylcellulose, hydroxypropylmethylcelluose,
hydroxyethylcellulose, ethylcellulose,
carboxymethylcellulose, dextran, polyvinylpyrrolidone, pectins, starches, gelatin, casein, acrylic acids, acrylic esters and their copolymers, vinyl polymers or copolymers, vinyl alcohols, alkoxypolymers, polyethylene oxide polymers and polyethers, or a mixture thereof.
The active pR1nciple may also be formulated in the form of microcapsules, optionally with one or more vehicles or additives.
The active pR1nciple may also be in the form of a complex with a cyclodextR1n, for example α-, β- or

y-cyclodextR1n, 2-hydrcrxypropyl-β-cyclodextR1n or methyl-β-cyclodextR1n.
The active pR1nciple may also be released by a small balloon containing it or by an endovascular expander introduced into blood vessels. The pharmacological efficacy of the active pR1nciple is thus not adversely affected.
Subcutaneous administration is the preferred route.
The following methods, preparations and schemes illustrate the synthesis of the vaR1ous intermediates which are useful for obtaining the polysaccharides according to the invention.
The examples below also illustrate the invention without, however, limiting it.
The following abbreviations are used: TBDMS: tert-butyldimethylsilyl; Lev: levulinyl; Bn: benzyl; Bz: benzoyl; TLC: thin-layer chromatography; 01m: tR1chloroacetimidyl; LSIMS: Liquid Secondary Ion Mass Spectrometry; ESIMS: Electron Spray Ionization Mass Spectrometry; TMS: tR1methylsilyl; TSP: sodium tR1methylsilyltetradeuteR1opropionate; Tf: tR1flate; MS: molecular sieves; All: allyl; PMB: p-methoxybenzyl; SE: tR1methylsilylethyl,
Dowex®, Sephadex®, Chelex® and Toyopearl® are registered trademarks.
In the methods, the preparations and in the examples descR1bed below, general procedures relating to catalytic coupling of the imidates, cleavage of the levulinic esters, catalytic coupling of the thioglycosides, saponification, methylation and selective deprotection of the p-methoxybenzyl group, the deprotection and sulphation of the oligo- and polysaccharides by hydrogenolysis of the benzyl ethers or of the esters, saponification of the esters or sulphations may be performed applying the general methods below to the appropR1ate intermediates.

GENERAL METHODS METHOD 1. Coupling to imidates catalysed by tert-butyldimethylsilyl triflate.
A solution of tert-butyldimethylsilyl triflate in dichloromethane (IM, 0.2 mol/mol of imidate) is added, under argon and at -20°C, to a solution of the imidate and the glycosyl acceptor in dichloromethane (17.5 ml/mmol) in the presence of 4 A molecular sieves. After 1O-20 minutes (TLC), solid sodium hydrogen carbonate is added. The solution is filtered, washed with water, dR1ed and evaporated to dryness. METHOD 2. Cleavage of the levulinic group.
The compound to be deprotected is dissolved in a 2/1 ethanol/toluene mixture (42 ml/mmol) and hydrazine acetate (5 mol/mol) is added. The mixture is left stirR1ng for 15-30 minutes (TLC) and concentrated. METHOD 3. Coupling to the thioglycosides catalysed by N-iodosuccinimide/silver triflate.
The thioglycoside and the glycosyl acceptor are dissolved in anhydrous toluene (18 ml/mmol of thioglycoside) in the presence of 4 A molecular sieves in a round-bottomed flask made of inactinic glass. The mixture is stirred for 1 hour at room temperature. It is cooled to 0°C and N-iodosuccinimide (3 mol/mol of thioglycoside) is added, followed by silver triflate (0.28 mol/mol of thioglycoside). After 1O-15 minutes (TLC), solid sodium hydrogen carbonate is added. After filtration, the solution is washed with aqueous IM sodium thiosulphate solution, water, dR1ed and evaporated.
METHOD 4. Saponification, methylation and selective deprotection of the p-methoxybenzyl group.
Saponification of the esters. The compound to be saponified is dissolved in a 1/1 dichloromethane/ methanol mixture (4 ml/mmol). Sodium methoxide is added and the mixture is stirred for 20 minutes and neutralized with a 50 H+ Dowex® resin. The solution is

concentrated and this compound is used in the following step without puR1fication.
Methylation, Sodium hydR1de is added portionwise, at 0oC, to a mixture of the above crude product and methyl iodide in N,N-dimethylformamide (7 ml/mmol). After complete reaction, the mixture is poured into water and extracted with ethyl acetate. The organic phases are washed with water, dR1ed and evaporated to dryness.
Cleavage of the p-methoxybenzyl. The above crude compound is dissolved in a 9/1 acetonitrile/water mixture (20 ml/mmol) . At O^'C, ammonium ceR1um nitrate (0.5 mol/mol) is added. The reaction mixture is stirred for 2 hours (monitored by TLC), saturated sodium hydrogen carbonate solution is added and the mixture is extracted with ethyl acetate, dR1ed and evaporated. METHOD 5. Deprotection and sulphation of the oligo- and polysaccharides.
Hydrogenolysis of the benzyl ethers and benzyl esters. A solution of the compound in glacial acetic acid is left stirR1ng for 6-12 hours (TLC) under a hydrogen atmosphere (40 bar) in the presence of 5 % Pd/C catalyst (twice the mass of the compound) . After filtration, the product is used directly in the following step.
Saponification of the esters. Aqueous 5 M sodium hydroxide solution (in an amount such that the concentration of sodium hydroxide is 0.5 M at the end of the addition) is added to a solution of an ester in methanol (150 ml/mmol). After 2-5 hours, water is introduced and the mixture is passed through a column of Sephadex® G-25 gel (1.6 x 115 cm) eluted with water. The eluate is concentrated, passed through a Dowex® 50 H"" column (2 ml) and freeze-dR1ed. At this stage, it is confirmed by 1H NMR that all the protecting groups have been removed. If necessary, the product is subjected to a further hydrogenation and/or saponification.
Sulphation. triethylamine/sulphur trioxide complex (5 mol/mol of hydroxy1 function) is added to a

solution of the compound to be sulpha ted in dimethylformamide (5 mg/ml) . After one day at 55oC/ the solution is placed at the top of a Sephadex® G-25 column (1.6 x 115 cm), eluted with 0.2 M sodium chloR1de. The fractions containing the product are concentrated and desalified using the same column eluted with water. The final compound is obtained after freeze-drying.



PREPARATION 1
Ethyl 2,4,6-tri-O-acetyl-3-O-methyl-l-thio-β-D-
glucopyranoside (2).
1,2,4,6-Tetrα-O-acetyl-3-O-methyl-β-D-glucopyranose 1 (69 g, 0.19 mmol), (B. HelfeR1ch et al., J. prakt. Chem., 132, 321 (1932)) is dissolved in toluene (580 ml). Ethanethiol (28 ml, 0.38 mmol) is added, followed by dropwise addition of a solution of trifluoroborane diethyl etherate (1 M in toluene, 190 ml). The mixture is left stirR1ng for 1.5 hours (TLC), solid sodium hydrogen carbonate is introduced and the mixture is filtered, washed with water, dR1ed and concentrated. Chromatography on a column of silica (3/1 cyclohexane/ethyl acetate) gives 2 (37 g, 54 %). [α]D -26 (c = 1. dichloromethane). 1H NMR (CDCl3) . 5 5.05-4.96 (m, 2H, H-2, H-4), 4.39, (d, IH, J = 9.5 Hz, H-1), 4.18-4,12 (m, 2H, H-6, H-6'), 3.60 (m, IH, H-5), 3.50 (dd, IH, J - 9.3 Hz, H-3), 3.41 (s, 3H, OCH3) , 2.65-2.53 (m, 2H, SCH2CH3) , 2.12, 2.11, 2.09 (3s, 9H, 3 Ac), 1.25 (t, IH, SCH2CH3) . PREPARATION 2
Ethyl 4,6-O-benzylidene-3-O-methyl-l-thio-β-D-
glucopyranosidtt (3).
Compound 2 (37 g, 0.1 mmol) is dissolved in a 1/2 mixture of methanol and dichloromethane (1.5 1). 2 M sodium methoxide solution (150 ml) is added. After 0.5 hour at room temperature, the mixture is neutralized with Dowex® 50 (H+) resin, filtered and
concentrated.
The above crude compound is dissolved in anhydrous acetonitrile (1 1) and a,α-dimethoxytoluene (30 ml, 0.2 mol) and camphorsulphonic acid (2.3 g, 10 mmol) are added. The mixture is left stirR1ng for 1.5 hours (TLC), triethylamine (1.4 ml) is added and the mixture is concentrated. The residue obtained is precipitated in ethyl ether and gives 3 (27 g, 81 %) . [α]D -60 (c = 1.63, dichloromethane). 1H NMR (CDCl3)

7.51-7.34 (m, 5H, Ph) , 5.55 (s, IH, CeHsCH) , 4.5 6 (d, IH, J = 9.2Hz, H-1), 2.75 (m, 2H, SCHsCifs) . 1.32 (t, 3H, SCH2CH3) .
Anal. Calculated for C16H22O5S (326.41) : C, 58.58; H, 6.79; S, 9.82. Found: C, 58.99; H, 6.74; S, 9.75. PREPARATION 3
Ethyl 2-O-bon2yl-4,S-O-benzylidone-S-O-methyl-l-thio-β-D-glucopyranoside (4).
Sodium hydR1de (2.00 q, 83.3 mmol) is added, at
0oC, to a solution of 3 (23 g, 71.0 mmol) and benzyl
bromide (11 ml, 93.0 mmol) in N,N-dimethylformamide
(200 ml) . The mixture is left stirR1ng for 2 hours
(TLC), methanol is added and the reaction mixture is
poured into water. It is extracted with ethyl acetate,
washed with water, dR1ed and concentrated. The residue
is precipitated in ethyl ether in order to obtain 4
(18.8 g, 63 %). m.p. 123°C. [α]D -35 (c - 0.63,
dichloromethane) . 1H NMR (CDCl3) 5 7.5O-7.25 (m, lOH,
2Ph), 5.55 (s, IH, CeHsCif) , 4.54 (d, IH, J = 9.7 Hz, H-
1), 4.34 (m, IH, H-6), 3.75 (t, IH, J = 10,2 Hz, H-6'),
3.65 (s, 3H, OCH3) , 3.6O-3.33, (m, 4H, H-5, H-4, H-3, H-
2), 2.75 (m, 2H, SCH2CH3) . 1.32 (t, 3H, SCHaCifa) .
Anal. Calculated for C23H28O5S (416.54): C, 66.32, H, 6.78; S, 7.70. Found: C, 66.25; H, 7.28; S, 7.54. PREPARATION 4
Ethyl 2,6-di-O-benzyl-3-O-methyl-l-thio-β-D-
glucopyranosida (5).
A solution of trifluoroacetic anhydR1de (0.65 ml, 4.50 mmol) in trifluoroacetic acid (16 ml, 0.21 mmol) is added, under argon, to a solution of 4 (28.8 g, 69.0 mmol) and triethylsilane (33 ml, 0.21 mmol) in dichloromethane (120 ml). The mixture is left stirR1ng for 2 hours and diluted with ethyl acetate and aqueous 1 M sodium hydroxide solution is added to pH 9. The mixture is extracted with ethyl acetate, washed with water, dR1ed and evaporated to dryness. The residue is puR1fied on a column of silica

f-
(3/1 and then 2/1 cyclohexane/ethyl acetate) in order o" obtain 5 (17.4 q, 60 %). [α]D -47 (c = 1, dichloromethane) . 1H NMR (CDCl3) 5 7.45-7.25 (m, lOH, 2Ph), 4.47 (d, IH, J = 9,3 Hz, H-1), 3.66 (s, 3H, OCH3) , 3.61-3.40 (m, 2H, H-4 and H-5) , 3.36-3.19 (m, 2H, H-2 and H-3), 2.73 (m, 2H, SCH2CH3) , 1.31 (t, 3H, SCH2CH2) .
Anal. Calculated for C23H30O5S (418,55) : C, 66.00, H, 7,22; S7.66. Found C, 65.62; H, 7,28; S, 7.21.
PREPARATION 5
Ethyl 2,6-O-di-benzyl-4-O-lovulinyl-3-O-methyl-l-thio-p-D-glucopyranoaide (6).
Compound 5 (17.3 g, 41.4 mmol) is dissolved in
anhydrous dioxane (400 ml). Levulinic acid (9.60 g,
83.0 mmol), 1-(3-dimethylaminopropyl)-3-
ethylcarbodiimide (16 g, 86 mmol) and 4-dimethylaminopyR1dine (1 g/ 8.3 mmol) are added. The mixture is left stirR1ng for 4 hours, extracted with ethyl acetate, washed successively with aqueous 5 % potassium hydrogen sulphate solution, with water, with saturated aqueous sodium hydrogen carbonate solution, with water, dR1ed and concentrated. The residue is puR1fied on a column of silica (6/1 toluene/ethyl acetate) in order to obtain pure 6 (19.9 g, 93 %). [α]d - 5 (c - 1.46, dichloromethane) . LSIMS, positive mode: m/z thioglycerol + NaCl, 539 (M+Na)+; thioglycerol + KF, 555 (M+K)^. 1H NMR (CDCl3) 5 7.4O-7.20 (m, lOH, 2Ph) , 4.92 (m, IH, H-4), 2.8-2.4 (m, 6H, SCH2CH3 and 0(C:0)CH2CH2(C:0)CH3) , 2.16 (s, 3H, 0(C:0)CH2CH2(C:0)CH3) , 1,32 (t, IH, J = 7.3 Hz, SCH2CH3) .
Anal. Calculated for CaaHssOiS (516.55): C, 65.09, H, 7.02; S, 6.21. Found: C, 65,30; H, 7.03; S, 5.75.
PREPARATION 6 Allyl 4,6-O-benzylidene-3-O-methyl-β-D-glucopyranoside
(7).
trifluoromethanesulphonic acid (1.10 ml, 0.012 mol) is added to a suspension of commercial 3-O-methylglucose (135 g, 0.7 mol) in allyl alcohol (1 1) ,

The mixture is heated at 120oC for 2 hours. It is neutralized by addition of triethylamine (2 ml) and evaporated to dryness.
α,α-Dimethoxytoluene (136 ml, 0.9 mol) and camphorsulphonic acid (25 g, 0.13 minol) are added to the above crude compound dissolved in N,N-dimethylformamide (2 1) . The mixture is heated at 80°C for 1 hour under vacuum. It is neutralized by addition of triethylamine (21 ml) and extracted with ethyl acetate, washed with water, dR1ed and concentrated in order to obtain a solid α/p mixture = 3/2, (144 g, 57 %), This mixture is recrystallized from ethanol in order to obtain pure 7-a (60 g, 26 %) . Chromatography
of part of the mother liquors on a column of silica (3/1 cyclohexane/ethyl acetate) gives pure 7-p (7.6 g), 7-a/p (6.8 g) and pure 7-a (1.4 g).
Compound 7-P: [α]D "43 (c = 1, dichloromethane). m.p.: 131°C. 1H NMR (CDCl3) 5 7.5O-7.2 6 (m, 5H, Ph) , 6.01-5.90 (m, IH, OCH2(CH:CH2) ) , 5.55 (s, IH, CeHsCff) , 5.38-5.32 (m, 2H, OCH2(CH:CH2) ) , 4.47 (d, IH, J -7.5 Hz, H-1) , 4.42-4.32 (m, 2H, H-6' and 0Ci?2 (CH :CH2) ) , 4.21^4.15 (m, IH, OCH2 (CHrCHa) ) , 3.80 (dd, IH, J = 10.2 Hz, H-6), 3.67 (s, 3H, OCH3) .
Anal. Calculated for C17H22O6 (322.36) : C, 63.34; H, 6.88. Found: C, 63.23; H, 7.12.
PREPARATION 7
Allyl 2-O-acetyl-4,6-O-benzylidane-3-O-ni«thyl-β-D-gluco-
pyranosida (8).
7 (11.5 g, 35.7 mmol) is dissolved in dichloromethane (100 ml) and acetic anhydR1de (4.0 ml, 42.8 mmol), triethylamine (6.40 ml, 46.4 mmol) and 4-dimethylaminopyR1dine (440 mg, 3.60 mmol) are added. The mixture is left stirR1ng for 2 hours (TLC), washed successively with aqueous 5 % potassium hydrogen sulphate solution, with water, with saturated aqueous sodium hydrogen carbonate solution, with water, dR1ed and evaporated until a solid 8 (12.3 g, 95%) is obtained, m.p. 115°C. [α]D -68 (c = 1, dichloro-

methane). LSIMS, positiv4 mode: m/z thioglycerol + NaCl, 387 (M+Na)+; thioglycerol + KF, 403 (M+K)+. 1H NMR
(CDCl3) 5 7.51-7.34 (m, 5H, Ph), 5.98-5.78 (m, IH, OCH2(CH:CH2) ) , 5.56 (s, IH, C6H5C6H5CH) , 5.32-5.17 (m, 2H, OCH2(CH:Cif2) ) , 4.99 (dd, J = 8 Hz, IH, H-2), 4.55
(d, J = 7.9 Hz, IH, H-1), 4.39-4.29 (m, 2H, H-6 and OC;f2{CH:CH2) ) , 4.14-4.04 (m, IH, OH2 (CH: CH2) ) 3.82 (t, J = 10.2Hz, IH, H-6'), 3.60 (s, 3H, OCH3) , 2.12 (s, 3H, Ac) .
Anal. Calculated for C19H24O7 (366.39): C, 62.63; H, 6.64. Found: C, 62.63/ H, 6.64.
PREPABATZON 8
Allyl 2-O-acetyl-6-O-benzyl-3-O-mathyl-β-D-glucopyrano-
side (9).
A solution of trifluoroacetic anhydR1de (306 fil, 2.10 mmol) in trifluoroacetic acid (10 ml) is added, at 0oC, to a solution of 8 (12.0 g, 33.3 mmol) and triethylsilane (21.3 ml, 133 mmol) in anhydrous dichloromethane (50 ml) . The mixture is left stirR1ng for 4 hours (TLC), diluted with ethyl acetate and aqueous IM sodium hydroxide solution is added to pH 9. The mixture is extracted with ethyl acetate, washed with water, dR1ed and concentrated. The residue is puR1fied on a column of silica (8/5 cyclohexane/acetone) to give pure 9 (10 g, 82 %) . [α]D -40 (c = 1.06, dichloromethane). 1H NMR (CDCl3) 6 7.35-7.28 (m, 5H, Ph) , 5.87-5.79 (m, IH, OCH2 (CH :CH2) ) , 5.28-5.14 (m, 2H, OCH2(CH:CH2) ) , 4.43 (d, IH, J = 7.9Hz, H-1), 4.41-4.28 (m, IH, OCH2 (CH:CH2) ) , 4.1O-4.02 (m, IH, OCff2(CH:CH2) , 3.77-3.75 (m, 2H, H-6 and H-6'), 3.51 (s, 3H, OCH3), 3.30 (dd, IH, J = 8.9Hz, H-3), 2.8 (d, IH, OH) ,
Anal. Calculated for C19H26O7 (366.39): C, 62.28/ H, 7.15. Found: C, 61.73: H. 7.19.



PREPARATION 9
Allyl 2-O-acetyl-6-O-benzyl-3-O-methyl-4-O-(2,6-di-O-benzyl-4-O-levulinyl-3-O-mothyl-α-D-glucopyranosyl)-β-D-glucopyranoside (10).
The thioglycoside 6 (17.4 q, 33.7 mmol) and the glycosyl acceptor 9 (10.3 q, 28.1 mmol) are dissolved in dichloroethane (150 ml) . 4 A molecular sieves are added and the mixture is left stirR1ng for 1 hour. A solution of N-iodosuccinimide (8.30 g, 33.7 mmol) and trifluoromethanesulphonic acid (0.30 ml, 3.30 mmol) in a mixture of dichloroethane and ethyl ether (415 ml, 1:1) is added, at -20oC and under an argon atmosphere. The mixture is left stirR1ng for 10 minutes (TLC) , sodium hydrogen carbonate is added and the mixture is filtered, washed successively with aqueous IM sodium thiosulphate solution, with water, with saturated aqueous sodium hydrogen carbonate solution, with water, dR1ed and concentrated. The residue is puR1fied on a column of silica (11/1 dichloromethane/ethyl acetate) in order to give the pure disaccharide 1O-a (11.7 g, 52 %) . [α]D + 38 (c = 1.01, dichloromethane) . 1H NMR (CDCl3) 5 7.35-7.23 (m, 15H, 3 Ph) , 5,9O-5.80 (m, IH, OCH2(CH:CH2) ) , 5.47 (d, IH, J = 3.6 Hz, H-1'), 5.27-5.14 (m, 2H, OCH2(CH:CH2) ) , 5.05-4.90 (m, 2H, H-4' and H-2), 4.42 (d, IH, J = 7.6 Hz, H-1), 4,38-4,32 (m, IH, OCH2(CH:CH2) ) , 4.15-4.0 (m, IH, OCH2(CH:CH2) ) , 3.90 (dd, IH, J = 8.8 Hz, H-4), 3.54, 3.34 (2 s, 6H, 2 OCH3) . 2.75-2.40 (m, 4H, 0 (C:0) CH2CH2 (C:0) CH3) , 2.16, 2.10 (2 s, 6H, Ac and 0 (C:0) CH2CH2 (C:0) CH3) .
Anal. Calculated for C45H56O14 (820.94) : C, 65.84; H, 6.88. Found: C, 65.74; H, 6.90. PREPARATION 10
Prop-1'-onyl-2-O-acetyl-6-O-benzyl-3-O-methyl-4-O-(2,6-di-O-benzyl-4-O-levulinyl-3-O-methyl-α-D-glucopyranoayl)-β-D-glucopyranoaida (11).
1,5-Cyclooctadienebis[methyldiphenylphos-phine] iR1dium hexafluorophosphate (5.80 mg, 0.70 μmol) is added to a solution of 10 (1.36 g, 1.66 mmol) in peroxide-free tetrahydrofuran (4.30 ml). The solution

is degassed, placed under an argon atmosphere and hydrogen is introduced. The mixture is left stirR1ng for 10 minutes (TLC) and evaporated. The residue is taken up in dichloromethane, washed with saturated aqueous sodium hydrogen carbonate solution, with water, dR1ed and concentrated. The residue is puR1fied on a column of silica (3/1 toluene/ethyl acetate) in order to obtain pure 11 (1.04 g, 76 %), [α]D + 47 (c = 1.1, dichloromethane). LSIMS, positive mode: m/z thioglycerol + NaCl, 951 (M + Na)+; thioglycerol + KF, 967 (M + K)+ 1H NMR (CDCl3) δ 7.34-7.23 (m, 15H, 3 Ph) , 6.21-6.16 (m, IH, 0 (CH:CH) CH3) , 5.45 (d, IH, J = 3.5 Hz, H-1'), 5.13-4.97 (m, 3H, H-4', H-2 and 0 (CH: Cif) CH3) , 4.6 (d, IH, J = 7.55 Hz, H-1), 3.96 (dd, IH, J = 8.9 Hz, H-4'). 3.54, 3.34 (2 s, 6H, 2 OCH3) , 2.74-2.36 (m, 4H, 0(C:0)CH2CH2(C:0)CH3) , 2.15, 2.08 (2s, 6H, Ac and 0{C:0)CH2CH2{C:0)CH3) 1.56-1.51 (dd, 3H, 0 (CH : CH) CH3)
Anal. Calculated for C45H56O14 (820.94) : C, 65.84; H, 6.88. Found: C, 66.21; H, 6.92. PREPAHATIOM 11
2-O-Acetyl-6-O-benzyl-3-O-methyl-4-O-(2,6-di-O-benzyl-4-O-levulinyl-3-O-methyl-α-D"-glucopyranosyl) -a,p-D-glucopyranose (12).
A solution of mercuR1c chloR1de (3.9 g, 14.3 mmol) in a mixture of acetone and water (26 ml, 5/1) is added dropwise to a solution of 11 (7.8 g, 9.53 mmol) and mercuR1c oxide in the same solvent (80 ml) . The mixture is left stirR1ng for 1 hour, filtered and concentrated. It is extracted with dichloromethane and the extracts are washed with saturated aqueous potassium iodide solution, with water, dR1ed and concentrated. The residue is puR1fied on a column of silica (10/1 and then 4/1 dichloromethane/acetone) in order to obtain 12 (6.70 g,
90 %) .
[α]D + 92 (c = 1.37, dichloromethane) . TLC, RF 0.31, 14/1 dichloromethane/acetone. 1H NMR (CDCl3) δ 7.37-7.24 (m, 15H, 3 Ph), 5.46 (d, IH, J = 3.5 Hz, H-1'), 5.37 (d, J = 3.6 Hz, H-la), 4.58 (d, J = 8 Hz, H-lp), 3.54,

3.39, 3.36 (3s, 6H, 2 OCH3) , 2.75-2.4 (m, 4H, 0(C,:0)CH2CH2(C:O)CH3) , 2.16, 2.15 (2s,6H,Ac and 0 (C:O)CH2CH2(C:O)CH3) , 2,16, 2.15 (2s, 6H, Ac and 0(C:O)CH2CH2(C:O)CH3) .
Anal. Calculated for C42H52O14 (780.83); C, 64.60; H, 6.71. Found: C, 65.09; H, 6.82. PREPARATION 12
2-O-Acetyl-6-O-benzyl-3-O-methyl-4-O-(2,6-di-O-bonzyl-4-O-levulinyl-3-O-methyl-α-D-glucopyranosyl)-a,p-D-glucopyranose trichloroacetimidate (13).
Compound 12 (5.00 g, 6.4 mmol) is dissolved in
dichloromethane (50 ml) and trichloroacetonitrile
(3.9 ml, 38.8 mmol) and potassium carbonate (1.5 g,
11.6 mmol) are added, under argon. The mixture is left
stirR1ng for 16 hours (TLC) and filtered. The filtrate
is puR1fied on a column of silica (8/1 and then 4/1
dichloromethane/acetone) in order to give a mixture
(a/p = 60/40) of imidates 13 (5.22 g, 87 %). TLC, RF
0.66 and 0.51, 20/1 dichloromethane/acetone. -1H NMR
(CDCl3) δ 8.62-8.59 (2s, IH, N:H-a and p), 7.37-7.23 (m,
15H, 3 Ph) , 6.51 (d, J = 3.7 Hz, H-la) , 5.81 (d, J =
7.1 Hz, H-IP) , 5.50 (d, IH, J = 3.5 Hz, H-1') , 3.55,
3.41, 3.37 (3s, 9H, 3 OCH3) , 2.75-2.40 (m, 4H,
0(C:O)CH2CH2(C:O)CH3) , 2.16, 2.07, 2.04 (3s, 6H, Ac and
(C:O)CH2CH2(C:O)CH3) .
Anal. Calculated for C44H52CI3NO14 (925.26): C, 57.12; H, 5.66; N, 1.51. Found: C, 57.31; H, 5.87; N, 1.55.
PREPARATION 13
Allyl 2-O-acetyl-6-O-benzyl-3-O-methyl-4-O-(2,6-di-O-bon2yl-3-O-methyl-α-D-glucopyranosyl)-β-D-glucopyranoside (14).
Compound 10 (3.11 g, 3.80 mmol) is treated according to Method 2 in order to give 14 (2.70 g, 97 %) . [α]D + 25 (c = 1.7, dichloromethane). LSIMS, positive mode: m/z thioglycerol + NaCl, 745 (M+Na)+; thioglycerol + KF, 761 (M+K)+. 1H NMR (CDCl3) d 7.33-7.20 (m, 15H, 3 Ph) , 5.87-5.78 (m, IH, OCH2 (CH:CH2) ) , 5.50 (d, IH, J = 3.5 Hz. H-1'), 5.3O-5.17 (m, 2H,

OCH(CH:Cff2) ) , 5.02 (dd, (H, H-2), 4.43 (d, IH, J = 7.6 Hz, H-1), 4.34-4.28 (m, IH, 0CH2 (CH: CH2) ) , 4.12-4.02 (m, IK, OCH2(CH:CH2) ) , 3.63, 3.36 (2s, 6H, 2 OCH3) , 2.10 (3, 3H, Ac).
Anal. Calculated for C40H50O12 (722.84); C,
6 6.4 7; H, 6.97. Found: C, 66.31; H, 7.24,



PREPAIIATION 14
Allyl O-(2,6-di-O-benzyl-4-O-levulinyl-3-O-methyl-α-D-glucopyranosyl) - (1^4) -O- (2-O-acetyl-6-O-benzyl-3-O-methyl-β-D-glucopyranosyl) - (1-^4) -O- (2, 6-di-0"benzyl-3-O-methyl-α-D-glucopyranosyl) - (1→4) -2-O-acotyl-6-O-benzyl-3-O-niothyl-β-D-glucopyranosido (15) .
A mixture of the imidate 13 (4.22 g, 4.56 mmol) and the glycosyl acceptor 14 (2.63 g, 3.64 mmol) is treated according to Method 1. The product is puR1fied on a column of silica (3/2 and then 1/1 toluene/ethyl ether) in order to give the tetrasaccharide 15 (4.31 g, 80 %) . [αlo + 52 (c = 0.66, dichloromethane) . 1H NMR (CDCl3) 6 7.35-7.23 (m, 30H, 6 Ph) , 5.83-5.79 (m, IH, OCH2(Cff:CH2) ) , 5.47 (d, 2H, J = 3.5 Hz, H-1'" and H-1'), 5.25-5.14 (m, 2H, OCH2 (CH :CH2) ) , 4.38 (d, IH, J = 7.7 Hz, H-1"), 4.30 (d, IH, J = 8 Hz, H-1), 4.32-4.25 (m, IH, OCH2(CH:CH2) ) , 4.08-4.02 (m, IH 0Cif2 (CH rCHa) ) , 3.56, 3.53, 3.34, 3.27 (4s, 12H, 4 OCH3) , 2.78-2.4 0 (m, 4H, 0(C:O)Cff2CH2(C:O)CH3) , 2.15, 2.09, 1.85 (3s, 9H, 2 Ac and 0 (C :0) CH2CH2 (C :0) CH3) .
Anal. Calculated for C82H100O25 (1485.7): C, 66.29; H, 6.78. Found: C, 66.10; H, 6.79. PREPARATION 15
O- (2,6-Di-'O-b«nzyl-4-O-levulinyl-3-O-xBothyl-α-D-glucopyranosyl) - (l->4) -O- (2-O-acotyl-6-O-b«nzyl-3-O-methyl-β-D-glucopyranosyl)- (l->4) -O-(2,S-di-O-baznyl-S-O-mothyl-α-D-glucopyranoayl) - (1^4) -2-O-acatyl-6-O-benzyl-3-O-methyl-a,p-D-glucopyranosa (16).
Compound 15 (2.30 g, 1.54 mmol) is treated as in Preparation 10. After 10 minutes, a solution of N-bromosuccinimide (0.30 g, 1.70 mmol) in dichloromethane (15 ml) and water (5.50 ml) is added to the reaction mixture. The mixture is left stirR1ng for 5 minutes (TLC) . It is diluted with dichloromethane, washed with saturated aqueous sodium hydrogen sulphate solution, with water, dR1ed and concentrated. The residue is puR1fied on a column of silica (3/2 toluene/ethyl acetate) in order to give pure 16 (1.57 g, 71% over the two steps) . [α]o +69 (c = 0.87, dichloromethane) .

11H NMR {CDCl3) S 7,38-7.20{m, 30H, 6 Ph) , 5.47 (d, IH, J = 3.5 Hz, H-1"' and H-1'), 5.36 (d, IH, J = 3.5 Hz, H-la) , 4.55 (d, IH, J = 8 Hz, H-1), 4.36 {d, IH, J = 8 Hz, H-1"), 3.56, 3.54, 3.39, 3.36, 3.28 (5s, 9H, 3 OCH3), 2.75-2.35 (m, 4H, 0 (C :0) CH2CH2 (C : 0) CH3) , 2.16, 2.13, 2.12, 1.86 (4s, 9H, 2 Ac and 0(C:O)CH2CH2(C:O)CH3) . PREPARATION 16
O- (2,6-Di-O-benzyl-4-O-levulinyl-3-O-iaothyl-α-D-glucopyranosyl) - (l->4) -O- (2-'O-acetyl-6-O-bonzyl-3-O-methyl-β-D-glucopyranosyl) - (l->4) -O- (2 , 6-di-O-b«nzyl-3-O-mothyl-α-D-glucopyranosyl) - (l->4) -2-O-acatyl-6-O-benzyl-3-O-methyl-a,P-D-glucopyranoa# trichloroacetimidata (17).
A mixture of 16 (1.5 g, 1.04 mmol), trichloroacetonitrile (0.63 ml, 6.22 mmol) and potassium carbonate (0.26 g, 1,87 mmol) in dichloromethane (15 ml) is left stirR1ng for 16 hours at room temperature. The solution is filtered and
concentrated. It is puR1fied on a column of silica (4/1
toluene/acetone + 1 7 of triethylamine) in order to
/ 00
give 17 (1.47 g, 89.6 %), TLC, R? 0.5 7/2 toluene/acetone. PREPARATION 17
Allyl O-(2,6-di-O-benzyl-3-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2-O-acatyl-6-O-benzyl-3-O-mathyl-β-D-glucopyranoayl) - (l->4) -O- (2, 6-di-O-b«nzyl-3-O-methyl-α-D-glucopyranosyl) - (1-^4) -2-O-acotyl-6-O-benzyl-3-O-mathyl-β-D-glucopyranosida (18).
The delevulination of 15 (1.3 g, 0.87 mmol) is carR1ed out according to Method 2 in order to give 18 (1.05 g, 86 %). [α]D +40 (c = 0.6, dichloromethane). 1H NMR (CDCl3) 6 7.36-7.23 (m, 30H, 6 Ph) , 5.83-5.78 (m, IH, OCH2(CH:CH2) ) , 5.50 (d, IH, J = 3.5 Hz, H-1''), 5.47 (d, IH, J = 3.5 Hz, H-1'), 5.25-5.21 (dd, IH, J = 1.6 Hz, J = 17 Hz, OCH2(CH:CH2) ) , 5.15-5.13 (dd, IH, J =
1.4 Hz, J = 10 Hz, OCH2(CH:CH2) ) , 4.38 (d, IH, J =
6.4 Hz, H-1"), 4.31 (d, IH, J = 6.5 Hz, H-1), 4.08-4.02

(m, IH, OCH2(CH:CH2) ) , 3.5§ (m, IH, H-4'"), 3.67, 3.53, 3.39, 3.29 (4s, 12H, 4 OCH3) , 2.09, 1.86 (2s, 6H, 2 Ac). PREPARATION 18
Allyl O- (2 , 6-di-O-benzyl-4-O-levulinyl-3-O-inethyl-α-D-glucopyranosyl) - (1—^4) - [O- (2-O-acetyl-6-O-benzyl-3-O-methyl-β-D-glucopyranosyl)- (1→4) -O-(2,6-di-O-benzyl-3-O-methyl-α-D-glucopyranosyl) - (l->4) ] 3-2-O-acetyl-6-O-benzyl-3-O-methyl-β-D-glucopyranoside (19).
A mixture of 18 (842 mg, 0.53 mmol) and 17 (1.17 g, 0.74 mmol) is treated according to Method 1. The product is puR1fied on a Toyopearl® HW-50 column (110 X 3.2 cm; 1/1 dichloromethane/ethanol) in order to give 19 (1.44 g, 85%). [α]D + 57 (c = 1.01, dichloromethane) . 1H NMR (CDCl3) d 7.35-7.20 (m, 60H, 12 Ph) , 5.83-5.78 (m, IH, OCH2 (Cif: CH2) ) , 5.24-5.21 (dd, IH, OCH2(CH:CH2) ) , 5.16-5.13 (dd, IH, OCH2 (CH rCHz) ) , 3.59, 3.56, 3.51, 3.47, 3.33, 3.26 (6s, 24H, 8 OCH3) , 2.75-2.35 (m, 4H, 0 (C :0) CH2Ci/2 (C :0) CH3) , 2.15, 2.09, 1.85, 1.84 (4s, 15H, 4 Ac and 0 (C :0) CH2CH2 (C :0) Cif3) ;
6 of the main anomeR1c protons: 5.48; 4.37;
4.29; 4.23 ppm.
Anal. Calculated for CO56047H188 (2815.51): C, 66.56; H, 6.73. Found: C, 66.22; H, 6.75.



PREPARATION 19
O-(2 , 6-Di-O-benzyl-4-O-levulinyl-3-O-methyl-α-D-glucopyranosyl)-(1-4)-[O-(2-O-acetyl-6-O-benzyl-3-O-methyl-β-D-glucopyranosyl)-(1-4)-O-(2,6-di-O-benzyl-3-O-methyl-α-D-glucopyranosyl) - (1-4) ]3-2-O-acetyl-6-O-benzyl-3-O-methyl-a,p-D-glucopyranose (20).
Compound 19 (720 mg, 0.25 mmol) is treated as in Preparation 15. The product is puR1fied on a column of silica (3/2 and then 4/3 toluene/ethyl acetate) in order to obtain 20 (555 mg, 78 %). [α]D +70 (c = 0.94, dichloromethane). TLC, RF 0.43, 1/1 toluene/ethyl acetate. PREPARATION 20
O- (2,6-Di-O-benzyl-4-O-lavTilinyl-3-O-methyl-α-D-glucopyranosyl)-(1-4)-[O-(2-O-acetyl-6-O-benzyl-3-O-methyl-β-D-glucopyranoayl)-(1-4)-O-(2,6-di-O-banzyl-3-O-methyl-α-D-glucopyranoayl) - (1-4) ] 3-2-O-acatyl-6-O-benzyl-3-O-mothyl-a,p-D-glucopyrano3a trichloroacetiaidate (21).
Compound 20 (540 mg, 0.195 mmol) is treated as in Preparation 16. The product is puR1fied on a column of silica (3/2 toluene/ethyl acetate + 1 % of
triethylamine) in order to give a mixture (a/p = 27/73) of the imidates 21 (455 mg, 80 %) . TLC, RF 0.48, 3/2 toluene/ethyl acetate. 1H NMR (CDCl3) δ 8.60, 8.59 (2s, IH, N:Ha and p) , 7.35-7.21 (m, 60H, 12 Ph) , 2.75-2.40 (m, 4H, 0(C:O)CH2CH2(C:O)CH3) , 2.16, 2.06, 2,04, 1.85, 1.84 (5s, 15H, 4 Ac and 0 (C:O) CH2CH2 (C:O) CH3) .
1H NMR (CDCl3) δ of the main anomeR1c protons: 6.50; 5.79; 5.51; 5.48; 4.29; 4.25 ppm.



PREPARATION 21
Phenyl 2,4,6-tri-O-acetyl-3-O-mothyl-l-thio-α-D-glucopyranosida (22).
1,2,4,6-Tetrα-O-acetyl-3-O-methyl-β-D-glucopyranose 1 (5.23 g, 14.4 mmol) is dissolved in toluene (45 ml). Thiophenol (3.0 ml, 28.8 mmol) is added, foil owed by dropwise addition of trifluoroborane diethyl etherate (1.77 ml, 14.4 mmol) and the mixture is then heated at 50°C for 0.5 hour. It is diluted with dichloromethane, washed with saturated aqueous sodium hydrogen carbonate solution, with water, dR1ed and concentrated. The residue is puR1fied on a column of silica (5/2 cyclohexane/ethyl acetate) to give 22-a (1.00 g, 17 %) and 22-p (2.71 g, 46 %) .
22-a, RF 0.44, 3/2 cyclohexane/ethyl acetate.
[α]D + 230 (c = 1, dichloromethane) . ESIMS, positive
mode: m/z + NaCl, 435 (M+Na)%- +KF, 451 (M+K)\ 1H NMR
(CDCl3) 5 7.46-7.27 (m, 5H, Ph) , 5.89 (d, IH, J =
5.6 Hz, H-1), 5.05-4.97 (m, 2H, H-2 and H-4), 4.49-4.42
(m, IH, H-5), 4.25-4.18 (m, IH, H-6), 4.05-4.00 (m, IH,
H-6'). 3.66, (dd, IH, J = 9.5 Hz, H-3) , 3.51 (s, 3H,
OCH3), 2.16, 2.12, 2.00 (3s, 9H, 3 Ac).
Anal. Calculated for C19H24O8S (412.46) : C, 55.33; H, 5.87; S, 7.77. Found: C, 55.25; H, 5.90; S, 7.75.
PREPARATION 22
Phenyl 4,6*O*benzylidenO-2,3-di-O-methyl-l-thio-α-D-glycopyranoside (23) .
Compound 22 (970 mg, 2.35 mmol) is dissolved in a 2/1 mixture of methanol and dichloromethane (18 ml) . 2M sodium methoxide solution (150 ml) is added. After 0,5 hour at room temperature, the mixture is neutralized with Dowex® 50 (H+) resin, filtered and concentrated.
a,α-Dimethoxytoluene (0.7 ml, 4.0 mmol) and camphorsulphonic acid (51 mg, 0.22 mmol) are added to the above crude reaction mixture in acetonitrile (22 ml) . The mixture is left stirR1ng for 1 hour.

neutralized by addition of triethylamine (0.50 ml) and concentrated.
Sodium hydR1de (73.0 mg, 2.80 mmol) is added, at 0°C, to a solution of the above crude product and methyl iodide (163 μ1, 4.0 mmol) in N,N-dimethylformamide (9 ml). The mixture is left stirR1ng for 1 hour and methanol is added. The mixture is extracted with ethyl acetate, washed with water, dR1ed and concentrated to obtain 23 in solid form (840 mg, 94 %). m.p.: 178°C. [α]D + 330 (c = 1, dichloromethane). ESIMS, positive mode: m/z + NaCl, 411.4 (M+Na)+, +KF, 427.4 (M+K)+, 1H NMR (CDCl3) S 7.5O-7.24 (m, lOH, 2 Ph) , 5.71 (d, IH, J = 3.4 Hz, H-1) , 5.52 (s, IH, C6H5CH) , 3.62 (s, 3H, OCH3) , 3.55 (s, 3H, OCH3) .
Anal. Calculated for C21H24O5S (388.48): C, 64.92; H, 6,23; S, 8.25. Found: C, 64.87; H, 6.17; S, 7.85.
PREPARATION 23
Phenyl 6-O-ban2yl-2,3-di-O-inothyl-l-thio-α-D-
glucopyranoside (24).
Compound 23 (792 mg, 0.47 mmol) is treated as in Preparation 4. The product is puR1fied on a column of silica (7/2 and then 2/1 cyclohexane/ethyl acetate) to give 24 (318 mg, 80 %). [α]D + 243 (c = 1, dichloromethane). ESIMS, positive mode: m/z + NaCl, 413 (M+Na)\- +KF, 429 (M+K)*. 1H NMR (CDCl3) δ 7.52-7.22 (m, lOH, 2 Ph), 5.71 (d, IH, J = 5.3 Hz, H-1), 3.64 and 3.49 (2s, 6H, 2 OCH3) , 3.36 (dd, IH, H-3) •
Anal. Calculated for C21H26O5S (390.50) : C, 64.59; H, 6.71; S, 8.21. Found: C, 64.05; H, 6.88; S, 7.74.
PREPARATION 24
Phenyl O- (2 , 6-di-O-benzyl-4-O-le'VTilinyl-3-O-methyl-α-D-glucopyranosyl) - (1-4) -O- (2-O-acetyl-6-O-banzyl-3-O-methyl-β-D-glucopyranosyl)-(1-4)-6-O-benzyl-2,3-di-O-methyl-l-thio-α-D-glucopyranoside (25).
A mixture of 13 (436 mg, 0.47 mmol) and 24 (153 mg, 0.39 mmol) is treated according to Method 1.

The product is puR1fied column (Sephadex® LH20, 1/1 ethanol/dichloromethane) to give pure 25 (30 9 mg, 68 %). [α]D -^ 144 (c = 1, dichloromethane) . ESIMS, positive mode: m/z + NaCl, 1175 (M+Na)%- +KF, 1191 {M+K)\ 1H NMR (CDCl3) δ 7.51-7.21 (m, 25H, 5 Ph) , 5.73 (d, IH, J = 5.2 Hz, H-1), 5.48 (d, IH, J = 3.5 Hz, H-1"), 4.46 (d, IH, J = 8 Hz, H-1'), 3.7, 3.54, 3.5, 3.31 (4s, 12H, 4 OCH3), 2.7O-2.41 (m, 4,H, 0(C:O)CH2CH2(C:O)CH3) , 2.16, 2,01 (2s, 6H, 1 Ac and
0(C:O)CH2CH2(C:O)Cff3) •
Anal. Calculated for C63H76O18S: C, 65.61; H,
6.64; S, 2.78. Found: C, 65.02; H, 6.60; S, 2.72. PREPARATION 25
Methyl O-(2,6-di-O-benzyl-4-O-levulinyl-3-O-mathyl-α-D-glucopyranosyl)-(1-4)-O-(2-O-ac«tyl-6-O-benzyl-3-O-mothyl-β-D-glucopyranosyl)-(1-4)-O-(6-O-b«nzyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(benzyl 2,3-di-O-methyl-β-D-glucopyranosyluronate)-(1-4)-O-(3,6-di-O-acetyl-2-O-bonzyl-α-D-glucopyranoayl)-(1-4)-O-(benzyl 2,3-di-O-methyl-α-L-idopyranosyluronate)-(1-4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (27).
A solution of N-iodosuccinimide (92 mg, 0.38 mmol) and triflic acid (37.5 |il, 0.38 mmol) in a 1/1 solution of 1,2-dichloroethane and ethyl ether (22 ml) is added, at -25°C and under argon, to a mixture of 25 (451 mg, 0.39 mmol) and 26 (434 mg, 0.31 mmol) , (P. Westerduin, et al. BioOrg. Med. Chem., 1994, 2, 1267) in 1,2-dichloroethane (7.5 ml) in the presence of 4 A molecular sieves (400 mg) . After 30 minutes, solid sodium hydrogen carbonate is added. The solution is filtered, washed with sodium thiosulphate solution, with water, dR1ed and evaporated. The residue is puR1fied on a column of Sephadex® LH-20 (1/1 dichloromethane/ethanol) and then on a column of silica (1/1 and then 2/3 cyclohexane/ethyl acetate) to give pure 27 (487 mg, 64 %) . [α]D + 63 (c = 0.54, dichloromethane), TLC, Rf 0.28, 2/1 cyclohexane/ethyl acetate. ESIMS, positive mode: m/z + NaCl, 2454 (M+Na)""; +KF, 2 4 69 (M+K)\ 1H NMR (CDCl3) 5 7.38-7.2 (m, 5 OH,

10 Ph), 3.56, 3.52, 3.48, 3.46, 3.44, 3.42, 3.39, 3.30, 3.17 (95, 27H, 9 OCH3) , 2.75-2.4 (m, 4H, 0(C:O)Cf/2CH2C:O)CH3) , 2.15, 1.98, 1.97, 1.87, (4s, 12H, 3 Ac and 0 (C :0) CH2CH2 (C :0) Cffs) ; main anomeR1c protons: 5.57; 5.47; 5.30; 5.18; 4.57; 4.29; 4.08. PREPARATION 26
Methyl O-(2,6-di-O-benzyl-3-O-methyl-α-D-glucopyranosyl)-(1-4)-(2-O-acetyl-6-O-bonzyl-3-O-methyl-β-D-glucopyranosyl)-(1-4)-O-(6-O-bsnzyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(benzyl 2,3-di-O-methyl-β-D-glucopyranosyluronate)-(1-4)-O-(3,6-di-O-acetyl-2-O-benzyl-α-D-glucopyranosyl)-(1-4)-O-(benzyl 2,3-di-O-methyl-α-L-idopyranosyluronate)-(1-4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (28).
The delevulinization of 27 (498 mg, 0.2 mmol) is carR1ed out according to Method 2 to give 28 (402 mg, 84 %). [α]o + 64 (c = 1, CH2CI2) . ESIMS, positive mode: m/z 2352.9 (M+NH4)*. 1H NMR (CDCl3) S 7.38-7.20 (m, 50H, 10 Ph) , 3.67, 3.52, 3.49, 3.46, 3.44, 3.41, 3.40, 3.28, 3.17 (9s, 27H, 9 Ac) , 2.65 (d, IH, J = 2.14 Hz, OH), 1.98, 1.96, 1.87 (3s, 9H, 3 Ac) ; main anomeR1c protons: 5.55; 5.49; 5.30; 5.18; 4.56; 4.31; 4.08.
Anal. Calculated for C127H152O41 (2334.48) : C, 65.34; H, 6.56. Found: C, 65.40; H, 6.62. PREPARATION 27
Methyl O-(2,6-di-O-banzyl-4-O-levulinyl-3-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(2-O-acetyl-6-O-b«nzyl-3-O-mothyl-β-D-glucopyranoayl)-(1-4)-[O-(2,6-di-O-benzyl-3-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(2-O-ac«tyl-6-O-bonzyl-3-O-methyl-β-D-glycopyranosyl) - (1-4) ]4-O- (6-O-benzyl-2,3-di-O-niethyl-α-D-glucopyranosyl) - (1-4) -O-(benzyl 2,3-di-O-methyl-β-D-glucopyranosyluronate)- (1-4)-O-(3,6-di-O-acetyl-2-O-benzyl-α-D-glucopyranosyl)-(1-4) -O- (benzyl 2,3-di-O-methyl-α-L-idopyranosyl\aronate) -(1-4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (29).
A mixture of 21 (340 mg, 1.16 mmol) and 28
(256 mg, 1.09 mmol) is treated according to Method 1.
The residue is puR1fied on a column of Toyopearl® HW-40

(3.2 X 70 cm, 1/1 dichloromethane/ethanol) to give the pure 15-mer 29 (421 mg, 76 %). [α]D +65 (c = 1, dichloromethane) . ESIMS, positive mode: m/z + KF, 2584.3 (M+2K)2+- 1736.5 (M+3K)3+1H NMR (CDCl3) δ 7.35-7.18 (m, 105H, 21 Ph), 2.75-2.4 (m, 4H, 0(C:O)C/f2CH2(C:O)CH3) , 2.15, 1.97, 1.95, 1.87, 1.84, 1.83 (6s, 24H, 7 Ac, and 0 (C : 0) CH2CH2 (C : 0) CH3) ; main anomeR1c protons: 5.55; 5.4 8; 5.30; 5.18; 4.56; 4.29; 4.22; 4.08.



PREPARATION 28
Methyl O-(2,6-di-O-benzyl-3-O-methyl-α-D-gluco-pyranosyl)-(1-4)-O-(2-O-acetyl-6-O-benzyl-3-O-methyl-β-D-glucopyranosyl)-(1-4)-[O-(2,6-di-O-benzyl-3-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(2-O-acetyl-6-O-benzyl-3-O-methyl-β-D-glycopyranosyl)- (1-4)]4-O-(6-O-benzyl-2,3-di-O-methyl-α-D-glucopyranoayl)-(1-4)-O-(benzyl 2,3-di-O-methyl-β-D-glucopyranosyluronate)-(1-4)-O-(3,6-di-O-acetyl-2-O-benzyl-α-D-glucopyranosyl)-(1-4)-O-(benzyl 2,3-di-O-methyl-α-L-idopyranosyluronate)-(1-4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (30).
Compound 29 (342 mg, 0.067 mmol) is treated according to Method 2 to give 30 (253 mg, 75 %). [α]D + 5 9 (c = 0.92, dichloromethane) . ESIMS, positive mode: m/z + KF, 2535.6 (M+2K)^\ 1H NMR (CDCl3) 6 of the main anomeR1c protons: 5.55; 5.50; 5.48; 5,30; 4.56; 4.30; 4.22; 4.08.
Anal. Calculated for C275H328O85 (4993.37): C, 65.57; H, 6.60. Found: C, 65.09; H, 6.57, PREPARATION 29
Methyl O-(2,6-di-O-benzyl-4-O-levulinyl-3-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(2-O-acetyl-6-O-benzyl-3-O-methyl-β-D-glucopyransoyl)-(1-4)-[O-(2,6-di-O-benzyl-3-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(2-O-acetyl-6-O-benzyl-3-O-methyl-β-D-glycopyranosyl)- (1-4)]e-O-(6-O-benzyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(benzyl 2,3-di-O-methyl-β-D-glucopyranoayluronate)- (1-4)-O-(3,6-di-O-acetyl-2-O-benzyl-α-D-glucopyranoayl)-(1-4)-(benzyl 2,3-di-O-methyl-α-L-idopyranosyluronate)-(1-4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (31).
A mixture of 17 (32.7 mg, 20.6 mmol) and 30 (80.7 mg, 16.3 mmol) is treated according to Method 1. The product is puR1fied on a column of Toyopearl® HW-40 (1/1 dichloromethane/ethanol) to give 19-mer 31 (60 mg, 59 %) . [α]D + 61 (c = 0,82, dichloromethane) . ESIMS, positive mode: m/z + NaCl, 2162.4 (M+3Na)3+- +KF, 2178.5 (M+3K)2+.
1H NMR (CDCl3) δ of the main anomeR1c protons:
5.55; 5.48; 5.30; 5.17; 4.56; 4.22; 4.08.



PREPARATION 30
Ethyl O-(4,6-O-benzylidene-α-D-glucopyranosyl)-(1-4)-6-
O-trityl-l-thio-β-D-glucopyranoside (33).
To a suspension of 32 (50.0 g, 0.105 mol)
(J. Westman and M. Nilsson, J. Carbohydr. Chem., 1995,
14(7), 949-960) in dichloromethane (620 ml) under argon
are added triethylamine (35 ml, 0.252 mol), trityl
chloR1de (29.3 g, 0.105 mol) and
4-dimethylaminopyR1dine (1.28 g, 10 mmol). The mixture is maintained at reflux for 2 hours (TLC), left to cool to room temperature, diluted with dichloromethane (500 ml) and then washed successively' with cold aqueous 10 % potassium hydrogen sulphate solution, with water and with saturated sodium chloR1de solution. The solution is dR1ed, concentrated and filtered on a column of silica (65/35 and then 50/50 toluene/acetone) in order to obtain the crude product 33, which is
sufficiently pure to be used in the following step. An analytic sample is chromatographed. [α]D +53 (c =
0.74, dichloromethane) . ESIMS, negative mode: m/z 715 (M-H)+. 1H NMR (CD2CI2) 5 7.52-7.25 (m, 20H, 4Ph) , 5.42 (s, CeHsCff) , 4.97 (d, J = 3.5 Hz, H-1') , 4.40 (d, J = 9.6 Hz, H-1), 3.82 (t, J = 9.3 Hz, H-3') , 3.70, 3.68 (m, 2H, H-3, H-4), 3.60 (dd, J « 2.0, 11.0 Hz, H-6a) , 3.55 (td, J = 5.2, 9.7, 9.7 Hz, H-5') , 3.49-3.45 (m, 3H, H-2, H-2', H-5), 3.38 (dd, J = 10.5 Hz, H-6'a), 3.33 (dd, H-6'b), 3.3O-3.27 (m, 2H, H-4', H-6b), 2.9O-2.77 (m, 2 H, SCH2CH3) , 1.4O-1.37 (t, 3H, CH2CH3) .
Anal. Calculated for C40H44O10S: C, 67.02; H, 6.19; S, 4.47. Found: C, 66.83; H, 6.19; S, 4.19. PREPARATION 31
Ethyl O- (4, 6*-O->banzylidene-2,3-di-O-mathyl-α-D-gluco-pyranosyl)-(1-4)-2,3-di-O-mothyl-6-O-trityl-l"thio-β-D-glucopyranoside (34) .
Methyl iodide (34 ml, 0.536 mol) is added dropwise, under argon, to a solution of compound 33 (64.1 g) in N,N-dimethylformamide (600 ml). The solution is cooled to 0°C and sodium hydR1de (13.5 g, 3.536 mol) is added slowly. The suspension is stirred


for 2 hours at room temperature and then cooled to 0°C
and methanol (35 ml) is added dropwise and, after stirR1ng for 2 hours, the mixture is diluted in ethyl acetate (500 ml) and water (600 ml). The aqueous phase is extracted with ethyl acetate and the organic phases are washed with water, dR1ed and concentrated. The residue 34 is sufficiently pure for the following step. An analytical sample is puR1fied on a column of silica (70/30 cyclohexane/acetone). [α]D + 45 (c = 0.83, dichloromethane). ESIMS, positive mode: m/z + NaCl, 795 (M+Na)%- +KF, 811 (M+K)+, 1H NMR (CDCl3) δ 7.52-7.19 (m, 20H, 4Ph), 5.51 (d, J = 3-3 Hz, H-1') / 5.43 (s, CeHsC/f) , 4.45 (d, J = 9.8 Hz, H-1), 3.60, 3.59, 3.51, 3.49 (4s, 12H, 4OCH3), 2.86 (q, 2H, J = 7.5 Hz, SCH2CH3) , 1.40 (t, 3H, SCH2CH3) .
Anal • Calculated for C44H52O10S: C, 68.37; H, 6.78; S, 4.15. Found: C, 68.28; H, 6.98; S, 4.09. PREPARATION 32
Ethyl O-(2,3-di-O-methyl-α-D-glucopyranosyl)-(1-4)-2,3-di-O-methyl-l-thio-β-D-glucopyranosida (35).
A suspension of crude product 34 (67.4 g) is heated at 80oC for 2 hours in aqueous 60 % acetic acid solution (470 ml)• The reaction mixture is cooled, filtered and concentrated. The residue is treated with sodium methoxide (940 mg) in methanol (200 ml) for 1 hour. The solution is then neutralized with Dowex® 50WX4 (H*) resin and then filtered, concentrated and puR1fied on a column of silica (60/40 toluene/acetone) in order to obtain 35 (27.9 g, 60 % over three steps). [α]D + 26 (c = 1.07, dichloromethane). ESIMS, positive mode: m/z, +NaCl, 465 (M+Na)+• +KF, 481 (M+K)+, 1H NMR (CDCl3) δ 5.62 (d, J = 3.9 Hz, H-1'). 4.35 (d, J = 9.8 Hz, H-1), 3.64, 3.64, 3.59, 3.58 (4s, 12H, 4OCH3) , 1.29 (t, 3H, J = 7.4 Hz, SCH2CH3) .
Anal. Calculated for C18H34O10S. H2O: C, 46.94; H, 7.87; S, 6.96. Found: C, 47.19; H, 7.72; S, 6.70.

PREPARATION 33
Ethyl O-(6-O-acetyl-2,3-di-O-methyl-α-D-gluco-pyranosyl)-(1-4)-6-O-acotyl-2,3-di-O-methyl-l-thio-β-D-glucopyranoside (36) .
A solution of triol 35 (5.86 g, 13.2 mmol) and N-acetylimidazole (3.21 g, 29.1 mmol) in 1,2-dichloroethane (120 ml) is refluxed for 16 hours. A further portion of N-acetylimidazole (440 mg, 3.96 mmol) is added and the mixture is stirred for 4 hours. It is left to cool to room temperature and methanol (2 ml) is then added. The mixture is stirred for a further 1 hour and then diluted with dichloromethane (1 1), washed successively with cold aqueous IM hydrochloR1c acid solution, with cold water, with saturated aqueous sodium hydrogen carbonate solution, with water, dR1ed and concentrated. The residue is chromatographed (3.5/1 toluene/acetone) in order to obtain the diacetate 36 (3.97 g, 57 %). [α]D + 33 (c = 1.90, dichloromethane) . ESIMS, positive mode: m/2, +NaCl, 549 (M+Na)%- +KF, 565 (M+K)+, 1H NMR (CDCl3) S 5.51 (d, J = 3.9 Hz, H-1'), 4.34 (d, J = 9.8 Hz, H-1), 3.64, 3.63, 3.59, 3.56 (4s, 12H, 4OCH3) , 2.11, 2.06 (2s, 6H, 2Ac), 1.31 (t, 3H, J = 7.4 Hz, SCH2CH3) .
Anal- Calculated for C22H38O12: C, 50.17; H, 7.27; S, 6.09. Found: C, 50.15; H, 7.49; S, 5.89. PREPARATION 34
Ethyl O-(6-O-acetyl-4-O-levulinyl-2,3-di-O-mothyl-α-D-glucopyranosyl)-(1-4)-6-O-ac«tyl-2,3-di-O-mathyl-l-thio-β-D-^glucopyranosida (37) .
To a solution of diacetate 36 (19.4 g, 36.8 mmol) in dioxane (400 ml), under argon, are added levulinic acid (7.53 ml, 73.5 mmol), l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloR1de (14.1 g, 73.5 mmol) and 4-dimethylaminopyR1dine (900 mg, 7.35 mmol). The mixture is stirred for 3.5 hours, diluted with dichloromethane (1.5 1) and then washed successively with water, with aqueous 10 % potassium hydrogen sulphate solution, with water, with aqueous 2 % sodium hydrogen carbonate solution, with

water and then dR1ed and concentrated. The residue is chromatographed (97/3 and then 79/21 dichloromethane/ acetone) in order to obtain the deR1vative 37 (21.8 g,
95 %) . [α]D + 40 (c = 0.72, dichloromethane) . ESIMS, positive mode: m/z, + NaCl, 647 (M+Na)+; +KF, 663
(M+K)+, 1H NMR (CDCl3) δ 5.56 (d, J = 3.9 Hz, H-1'), 4.35 (d, J = 9.8 Hz, H-1), 3.64, 3.60, 3.58, 3.55 (4s, 12H, 4OCH3) , 2.7 6-2.71 (m, 4H, 0 (C:O) CH2CH2 {C:O) CH3) , 2.19, 2.08, 2.07 (3s, 9H, 2Ac and 0 (C : 0) CH2CH2 (C :0) Cffa) , 1.31 (t, 3H, J = 7.4 Hz, SCHsCffs) .
Anal. Calculated for C27H44O14S: C, 51.91; H, 7.10; S, 5.13. Found: C, 51.88; H, 7.05; S, 4.96. SCHEME 10: Synthesis of dlsaccharides 38 and 40

PREPARATION 35
O-(6-O-Ac#tyl-4-O-levulinyl-2,3-di-O-inethyl-α-D-glucopyranosyl) -(1-4) -6-O-acetyl-2,3-di-O-niothyl-a,p-D-glucopyranosa trichloroacetimxdata (38).
To a solution of thioglycoside 37 (9.53 g, 15.3 mmol) in a 1/1 dichloromethane/ethyl ether mixture (180 ml) are added water (1.4 ml, 76.3 mmol), N-iodosuccinimide (6.84 g, 30.5 mmol) and silver triflate (0.51 g, 1.98 mmol). After 15 minutes (TLC) , saturated aqueous sodium hydrogen carbonate solution (5 ml) is added and the reaction mixture is diluted in dichloromethane (1.5 1), washed with water, aqueous IM sodium thiosulphate solution and aqueous 2 % sodium hydrogen carbonate solution. The solution is dR1ed and concentrated and the residue is puR1fied on a column of silica (80/40 and then 100/0 ethyl acetate/cyclohexane)

in order to give a solid which is used, without
characteR1zation, in the following step. A solution of
the above compound (7.88 q, 13.6 mmol) in
dichloromethane (120 ml) under argon is treated with caesium carbonate (7.08 g, 21.7 mmol) and trichloroacetonitrile (6.81 ml, 67.9 mmol). After 40 minutes (TLC), the mixture is filtered, concentrated and puR1fied (8 5/15 toluene/acetone) in order to obtain the imidate 38 (9.16 q, 83 % over two steps). [α]D + 118 (c = 1.00, dichloromethane) . ESIMS, positive mode: m/z +NaCl, 745 (M+Na)+,- 741 (M+NH4)^ 1H NMR (CDCl3) δ 8.66, 8.65 (2s, IH, a and P N:H), 6.52 (d, J = 3.6 Hz, H-la), 5.70 (d, J = 7.5 Hz, H-IP), 5.58 (d, J = 3.7 Hz, H-1' ) , 2.7 8-2.57 (m, 4H, 0 (C :0) CH2CH2 (C : 0) CH3) , 2.18, 2.07, 2.06 (3s, 9H, 2Ac and 0 (C :0) CH2CH2 (C : 0) Cffs) .
Anal. Calculated for C27H40CI3NO15- 0.5 H2O: C, 4 4.18; H, 5.63; N, 1.98. Found: C, 44.14; H, 5.61; N, 1.97.
PREPARATION 36
2- (trimethylsilyl)ethyl O- (6-O-acatyl-4-O-lavulinyl-2,3-di-O-m0thyl-α-D^glucopyranosyl)-(1-4)-6-O-acatyl-2,3-di-O-mothyl-a,p-D-glucopyranosida (39).
The thioglycoside 37 (10.6 g, 16.94 minol) is treated according to Method 3 with 2-(trimethylsilyl)ethanol (4.8 ml, 33.90 mmol) in a 1/2 dichloromethane/ethyl ether mixture (105 ml) . The residue obtained is puR1fied by chromatography (1/1 acetone/dichloromethane) in order to obtain compound 39 (9.80 g, 85 %) in the form of a mixture of anomers (a/p 65/35). ESIMS, positive mode: m/z +NaCl, 703 (M+Na)+, 1H NMR (CDCl3) δ 5.58 (d, J = 3.9 Hz, H-1') / 4.94 (d, J = 3.5 Hz, H-la), 4.26 (d, J = 7.7 Hz, H-lp) , 2.76-2.56 (m, 4H, 0(C:O)CH2CH2(C:O)CH3) , 2.17, 2.08, 2.05 (3s, 9H, 2Ac and 0 (C:O) CH2CH2 (C:O) CH3) , 1.18-0.88 (m, 2H, OCH2Cff2Si (CH3)3) , 0.02 (s, 9H, CH2CH2Si (CH3)3) .
Anal. Calculated for C3oH520i5Si: C, 52.92; H, 7.69. Found: C, 53.29; H, 7.75.



according to Method 3 in a 1/2 dichloromethane/ethyl ether mixture (105 ml). The residue is purified by chromatography on silica (3/1 and then 9/1 acetone/cyclohexane) in order to obtain 41 (4.81 g, 69 %) . [alo + 143 (c = 0.56, dichloromethane) . ESIMS, positive mode: m/z, + NaCl, 1167 (M+Na) %• + KF, 1183 (M+K) +, 'H NMR (CDCl3) 5 5,57 (d, J = 3. 9H2, H-1'" ) . 5.44, 5.41 (2d, J - 3.8H2, H-1", H-1') , 4,96 (d, J = 3. 6Hz, H-1) , 2.78-2.58 (m, 4H, 0(C:O) CffaCffa (C: 0) CH3) , 2.18, 2.12, 2.12, 2.09, 2.06, (5s, 15H, 4Ac and 0(C:O)CH2CH2(C:O)CJf3) / 1.21-0.97 (m, 2H, OCHsC/faSi (CH3) 3) , 0.03 (S, 9H, OCH2CH2Si (CHs) 3) .
Anal. Calculated for C5oH84027Si: C, 52.44; H, 7,39. Found: C, 52.29; H, 7.46

Ethyl O-(6-O-acatyl-4-O-lovulinyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(1-4)-[O-(6-O-acetyl-2,3-di-O-m0thyl-α-D-glucopyranosyl)- (1-4)-]2"6"(O-acetyl-2,3-di-O-methyl-1-thio-β-D-glucopyranosida (42).
A solution of imidate 38 (1.10 g, 1.52 mmol) and glycosyl acceptor 36(806 mg, 1,38 mmol) are treated in a 1/2 dichloromethane/ethyl ether mixture (22 ml) according to Method 1. The product is purified by chromatography on silica (2.5/1 and then 3/1 ethyl

acetate/cyclohexane) in order to obtain 42 (1.12 g, 71-,%). [α]D + 95 (c = 1.00, dichloromethane) . ESIMS,
positive mode: m/z, + NaCl, 1111 (M+Na)+; + KF, 1127 {M+K)+, 1H NMR (CDCl3) δ 5.55 (d, J = 3.9Hz, H-1'"), 5.39, 5.37 (2d, J = 3.8 and 3.9 Hz, H-1", H-1'), 4,34 (d, J = 9.7Hz, H-1), 2.84-2.51 (m, 6H, SCH2CH3, 0(C:O)CH2CH2(C:O)CH3) , 2.17, 2.10, 2.09, 2.08, 2.04, (5s, 15H, 4Ac and 0 (C :0) CH2CH2 (C :0) CH3) , 1.30(t,3H, J 7 .4Hz, SCH2CH3) .
Anal. Calculated for C47H76O26S: C, 51.83; H, 7.03; S, 2.94. Found: C, 51.66; H, 7.02; S, 2.94.



PREPARATION 40
2-(trimethylsilyl)ethyl [O-(6-O-acetyl-2,3-di-O-methyl-α-D-glucopyranosyl)- (1-4) -]3-6-O-acetyl-2,3-di-O-methyl-α-D-glucopyranoside (43).
Compound 41 (4.71 g, 4.11 mmol) is reacted as in Preparation 37 in order to obtain, after column chromatography (3/2 cyclohexane/acetone), the deR1vative 43 (4.11 g, 95 %). [α]^ + 154 (c = 0.63,
dichloromethane). ESIMS, positive mode: m/z, + NaCl, 1069 (M+Na)%' + KF, 1085 (M+K)+, 1H NMR (CDCl3) δ 5.46, 5.46 (2d, 3H, J = 3.9Hz, H-1', H-1", H-1'" ) , 4.95 (d, J = 3.5Hz, H-1), 2.81 (d, J = 4.4Hz, OH), 2.11, 2.09, 2.08 (3s, 12H, 4Ac) , 1.19-0.97 (m, 2H, OCH2CH2Si (CH3) 3) . 0.03, (s, 9H, OCH2CH2Si(Cff3)3) .
Anal. Calculated for C45H78025Si: C, 51.61; H, 7.51. Found: C, 51.39; H, 7.54.
PREPARATION 41
2-(trimethylsilyl)ethyl O-(6-O-acetyl-4-O-levulinyl-2,3-di-O-methyl-α-D-glucopyramosyl)-(1-4)-[O-(6-O-acetyl-2 , 3-di-O-methyl-α-D-glucopyranosyl) - (1-4) -] 6~6"* O-acetyl-2,3-di-O-methyl-α-D-glucopyranoside (44).
Thioglycoside 42 (3.86 g, 3.54 mmol) and the glycosyl acceptor 43 (3,60 g, 3.44 mmol) are treated according to Preparation 38. The product is chromatographed (7/2 and then 2/1 dichloromethane/acetone) in order to obtain 44 (5.71 g, 80 %) . [α]D + 161 (c = 0.65, dichloromethane). ESIMS, positive mode: monoisotopic mass = 2072.8, chemical mass = 2074,2, expeR1mental mass = 2074 ± 1 a.m.u. 1H NMR (CDCl3) δ 5.54, (d, J = 3.8Hz, H-1 unit NR) , 5.47-5.40 (m, 6H, H-1), 4.95 (d, J = 3,7H2, H-1 unit R) , 2.84-2.51 (m, 4H, 0 (C :0) CH2CH2 (C :0) CH3) / 2.17, 2.13, 2.12, 2.11, 2.11, 2.08, 2.05 (7s, 27H, 8Ac and 0(C:O)CH2CH2(C:O)Cif3, 1.18-0.97 (m, 2H, OCH2CH2si (CH3) 3) , 0.03 (s, 9H, OCH2CH2Si (CH3) 3) .
Anal. Calculated for C9oH14805iSi: C, 52.12; H, 7.19. Found: C, 51.98; H, 7.25.

PREPARATION 42
2-(trimethylsilyl)ethyl [O-(6-O-acetyl-2,3-di-O-methyl-α-D-glucopyranosyl)- (1-4)-]7-6-O-acetyl-2,3-di-O-methyl-α-D-glucopyranosido (45).
IM Hydrazine hydrate solution in a 3/2 acetic acid/pyR1dine mixture (7.3 ml) is added, at 0°C, to a solution of compound 44 (3.00 g, 1.45 mmol) in pyR1dine (5 ml) . After stirR1ng for 20 minutes, the reaction mixture is evaporated, diluted in dichloromethane (400 ml), washed with aqueous 10 % potassium hydrogen sulphate solution, water, aqueous 2 % sodium hydrogen carbonate solution and water. The solution is dR1ed and concentrated and the residue is chromatographed in order to obtain 45 (2.43 g, 85 %) . [α]D + 167 (c = 0.57, dichloromethane). ESIMS, positive mode: monoisotopic mass = 1974.8, chemical mass = 1976.1, expeR1mental mass = 1975.4 ± 2 a.m.u., 1H NMR (CDCl3) 5 5.47-5.40 (m, 7H, H-1), 4.95 (d, J = 3.7Hz, H-1 unit R) , 2.80 (d, J = 4.4Hz, OH), 2.13, 2.11, 2.10, 2.08, 2.07 (5s, 24H, 8Ac) , 1.18-0.97 (m, 2H, OCH2CH2Si (CH3) 3), 0.03 (s, 9H, OCH2CH2Si (CH3)3) .
Anal. Calculated for C85Hi42049Si: C, 51.66; H, 7.24. Found: C, 51.32; H, 7.26.
PREPARATION 43
2-(trimethylsilyl)ethyl O-(6-O-acetyl-4-0*levulinyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(1-4)-[O-(6-O-acetyl-2,3-di-O-methyl-α-D-glucopyrauiosyl) - (1-4) -]10-6-O-acetyl-2,3-di-O-methyl-α-D-glucopyranoside (46).
Compound 42 (1.35 g, 1.24 mmol) and compound 45 (2.38 g, 1.20 mmol) are treated according to Preparation 38. The residue is chromatographed (4/3 cyclohexane/acetone) in order to obtain 46 (2.56 g, 71%) . [α]D + 166 (c = 0.88, dichloromethane) . ESIMS, positive mode: monoisotopic mass = 3001.3, chemical mass = 3003.2, expeR1mental mass = 3004 ± 1 a.m.u. 1H NMR (CDCl3) δ 5.54, (d, J = 3.8Hz, H-1 unit NR) , 5.47-5.40, (m, lOH, H-1), 4.95 (d, J = 3.7H2, H-1 unit R) , 2.81-2.51 (m, 4H, 0 (C : 0) CH2CH2 (C :0) CH3) , 2.17, 2.13,

2.12, 2.11, 2.11, 2.08', 2.05 {7s, 39H, 12Ac and 0(C:O)CH2CH2(C:O)CH3) , 1.17-0.96 (m, 2H, OCHsCifsSi (CH3) 3) , 0.03 (s, 9H, OCH2CH2Si (CH3) 3) .
Anal. Calculated for Ci3oH2i2075Si: C, 51.99; H, 7.12. Found: C, 51.63; H, 7.12.
PREPARATION 44
(6-O-acetyl-4-O-lovulinyl-2,3-di-O-methyl-α-D-gluco-pyranosyl)-(1-4)~[O-(6-O-acetyl-2,3-di-O-methyl-α-D-glucopyranosyl) - (1-4) -]io-6-O-acatyl-2 ,3-di-O-methyl-a,[3-D-glucopyranosa trichloroacetxmldate (47) .
(a) A solution of glycoside 46 (400 mg, 0.133 mmol) in a 2/1 trifluoroacetic acid/dichloromethane mixture (2 ml) is stirred for 1,5 hours (TLC) . The solution is diluted in a 2/1 toluene/n-propyl acetate mixture (12 ml), concentrated and coevaporated with toluene (5 x 10 ml) . The residue is purified (4/3 acetone/cyclohexane) in order to obtain a solid (364 mg) .
(b) The solid obtained above is dissolved in dichloromethane (2.5 ml). Caesium carbonate (65 mg, 0.200 mmol) and trichloroacetonitrile (63 ml, 0.620 mmol) are added and the mixture is stirred for 2.5 hours and then filtered (Celite), concentrated and purified on a column of silica (50/50/0.1 cyclohexane/acetone/triethylamine) in order to obtain the imidate 47 (348 mg, 86 %) . [α]D + 185 (c = 0.91, dichloromethane). ESIMS, positive mode: monoisotopic mass = 3044.1, chemical mass = 3047.3, expeR1mental mass = 3046.9 ± 0.2 a.m.u. 1H NMR (CD2CI2) 5 8.61, 8.58
(2s, IH, a and P N:H), 6.35 (d, J = 3.7H2, H-la unit R), 5.59, (d, J = 7.5Hz, H-lb unit R) , 5.38 (d, J = 3.8Hz, H-1 unit NR), 5.32-5.25 (m, lOH, H-1), 2.64-2.40 (m, 4H, 0{C:O)CH2CH2{C:O)CH3) , 2.02, 1.96, 1.95, 1.94, 1.93, 1,89 (6s, 39H, 12Ac and 0 (C:O) CH2CH2 (C:O) CH3) .
Anal. Calculated for C127H200CI3NO25: C, 50.06; H, 6.61; N, 0.46. Found: C, 49.93; H, 6.52; N, 0.42.



PREPABATION 45
(6-O-acetyl-4-O-levulinyl-2,3-di-O-methyl-α-D-gluco-pyranosyl)-(1-4)-[O-(6-O-acetyl-2,3-di-O-methyl-α-D-glucopyranosyl) - (1-4) -] 2-6-O-acotyl-2 , 3-di-O-methyl-α, p-D-glucopyranose trichloroacatimidate (48).
Compound 41 (200 mg, 0.174 mmol) is treated according to Preparation 4 4. The reaction mixture is purified on a column of silica (3/2 toluene/acetone) in order to obtain the imidate 48 (230 mg, 77 %). ESIMS, positive mode: m/z, + NaCl, 1210 (M+Na) ^; + KF, 122 6 (M+K)+, 1H NMR (CDCl3) 5 8.66-8. 64 (2s, IH, a and p N:H), 6.51 (d, J = 3.6Hz, H-lp) , 5.71 (d, J = 7.5Hz, H-lp) , 2.9O-2.52 (m, 4H, 0 (C :0) CH2CH2 (C : 0) CH3) , 2.17, 2.11, 2.11, 2.09, 2.05 (5s, 4 Ac and 0{C:O)CH2CH2(C:O)CH3) .
PREPARATION 46
Mathyl O- (6-O-acatyl-4-O-levulinyl-2 , 3-di-O-methyl-α-D-glucopyranosyl) - (1-4) -[O- (6-"O-acotyl-2,3-di-O-methyl-α-D-glucopyranosyl) - (1-4) -] 2-O- (benzyl-2,3-di-O-methyl-β-D-glucopyranosyluronata)-(1-4)-O-(3,6-di-O-acatyl-2-O-benzyl-α-D-glucopyranoayl)-(1-4)-O-(benzyl-2,3-di-O-mothyl-α-L-ido-pyranosyluronate)-(1-4)-2,3,6-tri-O-benzyl-α-D-glucopyranosida (49) .
The imidate 48 (73 mg, 0.061 mmol) and the glycosyl acceptor 26 (82 mg, 0.059 mmol) are treated according to Preparation 39. The compound is purified on a Sephadex LH-20 chromatography column (1/1
dichloromethane/ethanol) and then on a column of silica
(3/1 toluene/acetone) to give the deR1vative 49 (98 mg,
69 %) . [α]D + 95 (c = 1.01, dichloromethane) . ESIMS,
positive mode: monoisotopic mass = 2414.97, chemical
mass = 2416.97, expeR1mental mass = 2416.2. 1H NMR
(CDCl3) 5 7.43-7.20 (m, 30H, 6Ph), 5.55 (d, J = 3.9H2,
H-1 unit NR), 5.50 (d, J = 3.9Hz, H-1 unit NR-3), 5.44,
5.38 (2d, J = 3.7 and 3.9Hz, H-1 unit NR-1, unit NR-2),
5.29 (d, J = 6.8H2, H-1 unit R-1), 5.17 (d, J = 3.5Hz,
H-1 unit R-2), 4.56 (d, J - 3.7H2, H-1 unit R) , 4.10
(d, J = 7.9Hz, H-1 unit R-3), 2.81-2.50 (m, 4H,

0(C:O)CH2CH2(C:O)CH3) , 2/l7, 2.15, 2.11, 2.09, 2.05, 2.00 (7s, 21H, 6Ac and 0 (C : 0) CH2CH2 (C : 0) CH3) .
Anal. Calculated for C120H158CI3O51: C, 5 9.63; H, 6.59. Found: C, 59,23; H, 6.58.
PREPARATION 47
Methyl[O-(6-O-acetyl-2,3-di-O-methyl-α-D-glucopyrano-syl) - (1-4) -] 3"O- (benzyl-2 , 3-di-O-methyl-β-D-glucopyrano-syluronate)-(1-4)-O-(3,6-di-O-acetyl-2-O-benzyl-α-D-glucopyranosyl)-(1-4)-O-(banzyl-2,3-di-O-methyl-α-L-idopyranosyluronato)-(1-4)-2,3,6-tri-O-benzyl-α-D-glucopyranosidtt (50).
The octasaccharide 49 (120 mg, 0.050 mmol) is
reacted as in Preparation 37. The residue is purified
on a column of silica (3/1 toluene/acetone) in order to
obtain compound 50 (95 mg, 83 %) . [α]D + 80 (C = 0.62,
dichloromethane). ESIMS, positive mode: monoisotopic
mass = 2316.9, chemical mass = 2318.4, expeR1mental
mass = 2318.2 ± 0.4 a.m.u. 1HNMR (CDCl3) δ 7.42-7.12
(m, 30H, 6Ph), 5.50, 5.46, 5.43, 5.40 (d, J = 3.9, 3.9,
3.7, 3.7Hz,
H-1 unit NR, unit NR-1, unit NR-2, unit NR-3) , 2.14, 2.10, 2.09, 2.08, 2.00, 1.88 (6s, 18H, 6Ac).
Anal, Calculated for C115H152O49: C, 5 9.57; H, 6.60. Found: C, 59.49; H, 6.61.



PREPARATION 48
Methyl O-(6-O-acetyl-4-O-levulinyl-2,3-di-O-methyl-α-D-glucopyranosyl) - (1-4)-[O-(6-O-acetyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(1-4) -] 15-O- (benzyl-2,3-di-O-methyl-β-D-glucopyranosyluronata)-(1-4)-O-(3,6-di-O-acetyl-2-O-benzyl-α-D-glucopyranosyl)-(1-4)-O-(benzyl-2,3-di-O-methyl-α-L-ido-pyrauiosyluronate)-(1-4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (51).
The imidate 47 (84 mg, 0.027 mmol) is treated with the glycosyl acceptor 50 (62 mg, 0.027 mmol) according to Preparation 39. The residue is first purified on a column of Toyopearl HW-4 0 and then on a
column of silica (1/1 cyclohexane/acetone) in order to obtain the deR1vative 51 (71 mg, 51 % not optimized) . [α]D + 136 (c = 0.95, dichloromethane) . ESIMS, positive mode: monoisotopic mass = 5200.11, chemical mass = 5203.39, expeR1mental mass = 5203.5. 1H NMR (CDCl3) δ 7.42-7.18 (m, 30H, 6Ph) , 5.54 (d, J = 3.8Hz, H-1 unit NR) , 5.51-5.40 (m, 15 H-1), 5.30 (d, J = 6.8Hz, H-1 unit R-1), 5.17 (d, J = 3.5Hz, H-1 unit R-2), 4.56 (d, J = 3.7Hz, H-1 unit R), 4.09 (d, J = 7.9Hz, H-1 unit R-3) , 2.85-2.53 (m, 4H, 0 (C:O) CH2CH2 (C:O) CH3) , 2.17, 2.16, 2.13, 2.11, 2.08, 2.05, 2.00, 1.88 (8s, 57H, 18Ac and
0(C:O)CH2CH2(C:O)CH3) .
Anal. Calculated for C24oH350O123.4H2O: C, 54.64 ; H, 6.84. Found: C, 54.51; H, 6.79.



PREPARATION 49
Ethyl O- (4 , 6-O-β-inethoxybenzylidene-α-D-glucopyrano-
syl)-(1-4)-l-thio-β-D-glucopyrano3ide (53).
Anisaldehyde dimethyl acetal (35.8 ml, 0.21 mol) and camphorsulphonic acid (4.44 g, 19,1 mmol) are added, at +5°C and under argon, to a solution of compound 52 (73.89 g, 0.19 mmol) (W.E. Dick Jr et J.E. Hodge, Methods in Carbohydrate Chemistry, 7, 1976, 15-18) in a 3.5/1 acetonitrile/N,N-dimethylformamide mixture (990 mmol) . After stirR1ng for 1.5 hours at room temperature, the mixture is neutralized by addition of triethylamine (2.96 ml, 21.0 eq.). The mixture is concentrated and the syrup is purified on a column of silica (100/0 and then 50/50 dichloromethane/methanol) in order to obtain 53 (58.6 g, 61 %, not optimized). [α]D + 47 (c = 1.03, methanol). ESIMS, positive mode: m/z, 503 (M-H)'. 1H NMR (CD3OD) 5 7,41, 6.89 (2d, 4H, CH3OC6/f4) / 5.51 (s, CHC34) f 5.20 (d, J = 3.6Hz, H-1'), 4.39 (d, J = 7.1Hz, H-1) , 3.7 8 (s, 3H, Cff30C6H4) , 2.75 (q, 2H, J = 7.0Hz, SCH2CH3) , 1.29 (t, 3H, SCH2Cff3) .
Anal. Calculated for C22H32O11S: C, 52.37; H, 6.39; S, 6.35. Found: C, 52.15; H, 6,61; S, 5.84.
PREPARATION 50
Ethyl O- (2,3-di-O-aceyl-4,6-β-mathoxybenzyliden«-α-D-glucopyranosyl)-(1-4)-2,3,6-tri-O-acetyl-l-thio-β-D-glucopyranoside (54).
triethylamine (65 ml, 0.47 mol) and acetic anhydride (89 ml, 0.94 mol) are added dropwise, at 0°C, to a suspension of 53 (47.22 g, 93.6 mmol) in dichloromethane (450 ml) . 4-DimethylaminopyR1dine (5.71 g, 46.8 mmol) is then added and the mixture is left stirR1ng for 1.5 hours at room temperature. The reaction is stopped by addition of methanol (45 ml, 1.12 mol) and then washed successively with cold aqueous 10 % potassium hydrogen sulphate solution, water, saturated sodium hydrogen carbonate solution and water. The solution is dried, concentrated and

crystallized (cyclohexanethyl acetate) in order to obtain 54 (64.9 g, 97 %). [α]o +21 (c = 1.00, dichloromethane) . pf 213-"215°C. ESIMS, positive mode: m/z + NaCl, 737 (M+Na)+, + KF, 753 (M+K)+, 1H NMR (CDCl3) δ 7,34, 6.86 (2d, 4H, CH3OCSH4) , 5.43 (s, CHC1H^) , 5.34 (d, J = 4.1Hz, H-1'). 4.54 (d, J = 9.9Hz, H-1), 3.78 is, 3H, CH3OCSH4) ,2.7 4-2.60 (m, 2H, SCffaCHa) , 2.10, 2.06, 2.03, 2.01 (4s, 15H, 5Ac) , 1.26 (t, 3H, SCH2Cif3) •
Anal. Calculated for C32H42O16S: C, 53.78; H, 5.92; S, 4.49. Found: C, 53.74; H, 6.08; S, 4.40.
PREPARATION 51
Ethyl O- (2,3-di-O-acotyl-4-β-mathoxybenzyl-α-D-gluco-
pyranosyl)-(1-4)-2,3,6-tri-O-acetyl-l-thio-β-D-gluco-
pyranoside (55) and ethyl O-(2,3-di-O-acotyl-4-β-
methoxybanzyl-α-D-gluGopyranosyl)-(1-4)-2,3-di-O-
acotyl-1-thio-β-D-glucopyranoside (56).
A suspension of 54 (25.0 g, 35.0 mmol),
borane/trimethylamine complex (20.4 g, 0.28 mol) and
molecular sieves (33 g, 4A) is stirred for 1 hour under
argon in toluene (810 ml). The mixture is cooled to 0*C
and aluminium chloR1de (14.0 g, 0.11 mol) is added
slowly. The reaction medium is stirred for 25 minutes
(TLC), poured into cold, aqueous 20 % potassium
hydrogen sulphate solution, stirred for 1 hour at 0°C
and then filtered (Celite) • The organic phase is washed
with water, with aqueous 2 % sodium hydrogen carbonate
solution, with water, dried and concentrated. The
ft
residue is purified on a column of silica in order to obtain 55 (7.37 g, 29 %, not optimized) and 56 (1.36 g, 6 %). An analytical sample of 55 is crystallized from a cyclohexane/ethyl acetate mixture, [α]D +30 (c = 1.00, dichloromethane) . m.p. 151-153o
C ESIMS, positive mode: m/z, + NaCl, 739 (M+Na)+, + KF, 755 (M+K)*. 1H NMR (CDCl3) δ 7.19, 6.87 {2d, 4H, CH3OC6H4) , 5.36 (d, J = 3.5Hz, H-1'), 4.54 (s, 2H, C6H4CH2) , 4.53 (d, J = 9.0Hz, H-1) , 2.7 O-2.65 (m, 2H, SCH2CH3) .
Anal. Calculated for C32H42O16S: C, 53.62; H, 6.19; S, 4.47. Found: C, 53.57; H, 6.21; S, 4.43,

Compound 56: [α]D + 19 (c = 1.11, dichloro-methane). ESIMS, positive mode: m/z + NaCl, 697 (M+Na)+, + KF, 713 (M+K)-. -H NMR (CDCl3) δ 7.17, 6.84 (2d, 4K, CH3OC5HJ , 5.3 6 (d, J = 4.5Hz, H-1' ) , 4.54 (d, J = IO.IH2, H-1) , 4 .49 (s, 2H, C6.CH2 , 2.69-2.64 (m, 2H, SCH2CH3) , 2.02, 2.01, 2.00, 1.96 (4s, 12H, 4Ac) , 1.2 5 (t, 3H, SCH2CH3) .
Anal. Calculated for C30CH42Os40; H, 6.27; S, 4.75. Found: C, 53.29; H, 6.39; S, 4.53.
PREPARATION 52
Ethyl O- (2,3-tri-O-acetyl-4-β-methoxybenzyl-α-D-gluco-pyranosyl)-(1-4)-2,3,6-tri-O-acetyl-l-thio-β-D-gluco-pyranoside (57).
Acetic anhydride (1.47 ml, 15.5 mmol) is added, at 0°C, to a mixture of 55 (5.6 g, 7.77 mmol), triethylamine (1.19 ml, 8,54 mmol) and 4-dimethylamino-pyR1dine (190 mg, 1.55 mmol) in dichloromethane (40 ml) . After stirR1ng for 40 minutes (TLC) at room temperature, the mixture is diluted with dichloromethane (50 ml) and washed with cold, aqueous 10 % potassium hydrogen sulphate solution, water, saturated sodium hydrogen carbonate solution and water. The solution is dried and concentrated and the residue is purified on a column of silica (35/65 ethyl acetate/cyclohexane) in order to obtain 57 (5.66 g, 96 %) . [α]D 44 (c = 1.03, dichloromethane). ESIMS, positive mode: m/z, + NaCl, 781 (M+Na) +, + KF, 7 97 (M+K)+, 'H NMR (CDCl3) δ 7.15, 6.85 (2d, 4H, CU,0C,HJ , 5.30 (d, J = 4.2Hz, H-1'), 4.53 (d, J = lO.OHz, H-1), 2.6 9-2.64 (m, 2H, SCH2CH3) , 2.09, 2.07, 2.04, 2.01, 2.00, 1.98 (6s, 18H, 6Ac) , 1.25 (t, 3H, SCH2CH3) .
Anal. Calculated for C34H46O17S. 52.82; H, 6.11; S, 4.22. Found: C, 53,77; H, 6.24; S, 4.09.


PREPARATION 53
Ethyl 4,6-O-benzylidene-2,3-di-O-methyl-l-thio-β-D-
glucopyranoside (59).
Sodium hydride (500 mg, 19.9 mmol) is added, at 0°C, to a mixture of compound 58 (2.59 g, 8.29 mmol) (A.F. Bochkov et al. , Izv. Akad. Nauk SSSR, Ser. Khim. (1968) , (1) , 179) and methyl iodide (1.70 ml, 19.9 mmol) in N,N-dimethylformamide (25 ml) and the mixture is allowed to return to a temperature of 20oC. The mixture is left stirR1ng for 30 minutes (TLC) and methanol is then added. The mixture is poured into water and extracted with ethyl acetate. The organic phase is washed successively with aqueous IM sodium thiosulphate solution and water, dried and concentrated. The residue is triturated in ethyl ether in order to obtain 59 (0.42 g, 15 %) ; purification of

the mother liquors on a column of silica (12/1 toluene/acetone) followed by crystallization allows an additional fraction of 59 (1.6 g, overall yield: 71 %) to be obtained, m.p.: 108°C. [α]D - 78 (c = 1.00, dichloromethane). LSIMS, positive mode: m/z thioglycerol + NaCl, 363 (M+Na)+,- thioglycerol + KF, 379
(M+K)+, 1H NNR (CDCl3) 5 7.51-7.33 (m, 5H, Ph) , 5.52 (s, IH, CgHsCH) , 4.45 (d, IH, J = 9.8Hz, H-1) , 3.64
(s, 3H, OCH3) , 3.62 (s, 3H, OCH3) , 2.78-2.68 (m, 2H, SCH2CH3) , 1.31 (t, 3H, J = 2.7Hz, SCH2CH3) .
Anal. Calculated for C17H24O5S (340.44) : C, 59,98; H, 7.11; S, 9.42. Found: C, 59.91; H, 7.15; S, 8.96.
PREPARATION 54
2-(trimethylsilyl)ethyl 4,6-O-benzylidene-2,3-di-O-
methyl-α-D-glucopyranoside (60).
Compound 59 (23.0 g, 67.5 mmol) and 2-
(trimethylsilyl)ethanol (19.4 ml, 135 mmol) are dissolved in a 2/1 mixture of ethyl ether and dichloromethane (345 ml) and 4 A molecular sieves (11 g) are added. The mixture is left stirR1ng for 1 hour at 25°C and N-iodosuccinimide (49.7 g, 220 mmol) is added, followed, at 0°C, by silver triflate (2.20 g, 8.78 mmol). The mixture is left stirR1ng for 20 minutes
(TLC), and solid sodium hydrogen carbonate is then added. The mixture is diluted with dichloromethane, filtered through Celite, washed successively with aqueous IM sodium thiosulphate solution and water, dried and evaporated to dryness. The residue is purified on a column of silica (15/1 and then 5/1 cyclohexane/ethyl acetate) in order to obtain 60p
(4.20 g, 15 %) and 60a (8.40 g, 31 %) .
Compound 60a. [α] D + 96 (c = 0.4, dichloromethane) . ESIMS, positive mode: m/z, 419 (M+Na)+; 435
(M+K)+, 1H NMR (CDCl3) 5 7.52-7.35 (m, 5H, Ph) , 5.54 (s, IH, CgHsCH) , 4.98 (d, IH, J = 3. 7Hz, H-1) , 3.64
(s, 3H, OCH3) , 3.62 (s,3H, OCH3) , 1.24-0.96 (m, 2H, OCH2CH2Si(CH3)3) , 0.00 (s, 9H, OCH2CH2Si (CH3) 3) .

Anal. Calculated for C20H32O6 (396.56) : C, 60.58; H, 8.13. Found: C, 60.26; H, 8.39.
PREPARATION 55
2-(trimethylsilyl)ethyl 6-O-benzyl-2,3-di-O-methyl-α-D-
glucopyranoside (61).
Compound 60 (21.1 g, 53.3 mmol) is dissolved in dichloromethane (154 ml). triethylsilane (34 ml, 213 mmol) is added at room temperature, followed by dropwise addition of a mixture of trifluoroacetic acid (16.3 ml, 213 mmol) and trifluoroacetic anhydride (0.49 ml, 3.47 mmol). The mixture is left stirR1ng for 2 hours and aqueous IM sodium hydroxide solution is added until the pH is basic. After separation of the phases by settling, the aqueous phase is extracted with ethyl acetate and the organic phases are then combined, dried and concentrated. The residue is purified on a column of silica (14/1 and then 12/1 dichloromethane/acetone) in order to obtain 61 (12.5 g, 59 %) . [α]D + 100 (c = 1.45, dichloromethane). 'H NMR 6 7.4O-7.20 (m, 5H, Ph) , 4.98 (d, IH, J = 3. 5Hz, H-1) , 3.62 (s, 3H, OCH3) , 3.4 9 (s, 3H, OCH3) , 1.14-0.91 (m, 2H, CH2CH2Si(CH3)3) , 0.00 (s, 9H, CH3CH3Si (CH3) 3) .
Anal. Calculated for C2oH3o06Si (398.58) : C, 60.27; H, 8.60. Found: C, 60.18; H, 8.81.
PREPARATION 56
2-(trimethylsilyl)ethyl O-(2,3,6-tri-O-acetyl-4-O-β-methoxybenzyl-α-D-glucopyranosyl) - (1-4)-O- (2,3,6-tri-O-acetyl-β-D-glucopyranosyl-(1-4)-6-O-benzyl-2,3-di-O-methyl-α-D-glucopyranoside (62).
A mixture of thioglycoside 57 (19.1 g, 25.1 mmol) and the glycosyl acceptor 61 (7.5 g, 18.7 mmol) is treated according to Method 3 in order to obtain, after purification on a column of silica (20/1 and then 10/1 dichloromethane/acetone), 62 (19.7 g, 95 %). [α]d +90 (c = 1.15, dichloromethane).
Anal. Calculated for C52H74023Si (10 95.24) : C, 57.03; H, 6.81. Found: C, 57.33; H, 6.85.















pyranosyl) - (1-4) ] 3-6-O-ben^yl-2, 3-di-O-methyl-a, p-D-glucopyranose (71) .
Compound 70 (876 mg, 0.41 mmol) is treated as in Preparation 44(a). The residue is purified on a column of silica in order to obtain a mixture of isomers (a/b = 60/40) of 71 (600 mg, 50 % over the two steps). [α]D +89 (c = 0.74, dichloromethane). ESIMS, positive mode: monoisotopic mass = 2028.97, chemical mass = 2 03 0.24, expeR1mental mass = 2030.19 ± 0.09 a.m.u. 1H NMR (CDCl3) δ 7.33-7.32 (m, 5H, Ph) , 5.65 (d, 3H, J = 3.8Hz H-1 unit NR, unit NR-2 and unit C) , 5.63 (d, IH, J = 3.8Hz, H-1 unit R-2), 5.33 (d, IH, J = 3.2Hz, H-la unit R) , 5.02 (t, IH, J = lO.lHz, H-4 unit NR), 4.59 (d, IH, J = 5.3Hz, H-lp unit R), 4.32 (d, IH, J = 7.9Hz, H-1 unit NR-1) , 4.30 (d, 2H, J = 7.9Hz, H-1 unit NR-3 and unit R-3) , 4.29 (d, IH, J = 7.9H2, H-1 unit R-1) , 2.8 O-2.50 (m, 4H, 0 (C:O) CH2CH2 (C:O) CH3) , 2.18 (s, 3H, 0(C:O)CH2CH2(C:O)CH3) .
PREPARATION 66
O- (4-O-Levulinyl-2,3,6-tri-O-methyl-α-D-gluco-pyranosyl) - (1-4) -O- (2, 3, 6-tri-O-methyl-β-D-gluco-pyranosyl) - (1-4) - [O- (2,3, 6-tri-O-methyl-α-D-gluco-pyranosyl)-(1-4)-O-(2,3,6-tri-O-methyl-β-D-gluco-pyranosyl) - (1-4) ] 3-6-O-benzyl-2, 3-di-O-methyl-α,β-D-glucopyranose trichloroacetlmidate (72).
To a solution of 71 (593 mg, 0.29 mmol) in dichloromethane (7 ml) are added potassium carbonate
(72.2 mg, 0.52 mmol) and trichloroacetonitrile (176 )il, 1.75 mmol) . The mixture is left stirR1ng for 16 hours, filtered and evaporated. The residue is filtered through silica gel (5/4 cyclohexane/acetone + 1 %o of triethylamine) in order to obtain a mixture of the anomers (a/p = 47/53) of the imidate 72 (414 mg, 46 %).
[α]D + 86 (c = 0.84, dichloromethane). 'H NMR (CDCl3) δ 7.33-7.32 (m, 5H, Ph) , 6.50 (d, IH, J = 3.5Hz, H-la unit R) , 5.65 (d, IH, J = 8.2Hz, H-lp, unit R) , 5.65
(d, IH, J = 3.8Hz, H-1 unit NR) , 5.64 (d, 2H, J = 3.8Hz, H-1 unit R-2 and unit C) , 5.61 (d, IH, J =

3.8Hz, H-1 unit R-2), 5.02 (t, IH, J = lO.lHz, H-4 unic NR; , 4.37 (d, IH, J = 7. 9Hz, H-1 unit R-1) , 4.30
(d, 3H, J = 7.9Hz, H-1 unit NR-1, unit NR-3 and unit R-3) , 2.8O-2.50 (m, 4H, 0 (C :0) CH2CH2 (C :0) CH3) , 2.18
(s, 3H, 0(C:O)CH2CH2(C:O)CH3) .



PREPARATION 61
Methyl O-(4-O-levulinyl-2,3,6-tri-O-methyl-α-D-gluco-pyranosyl) - (1-4)- [O-(2,3,S-tri-O-methyl-α-D-glucopyrano-syl)-(1-4)-O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl) - (1-4) ] 3-O- (6-O-benzyl-2, 3-di-O-inethyl-α-D-glucopyranosyl)-
(1-4)-O-(benzyl 2,3-di-O-methyl-β-D-glucopyranosyl-uronate)-(1-4)-O-(3,6-di-O-acetyl-2-O-benzyl-α-D-gluco-pyranosyl)-(1-4)-O-(benzyl 2,3-di-O-methyl-α-L-ido-pyranosyluronate)-(1-4)-2,3,6-tri-O-benzyl-α-D-gluco-pyranoside (73).
The glycosyl acceptor 26 (220 mg, 0.16 mmol) and imidate 72 (344 mg, 0.16 mmol) are dissolved in a 1/2 dichloromethane/ethyl ether mixture (5 ml) . 4 A molecular sieves (750 mg/mmol) are added and the mixture is left stirR1ng at 25°C for 1 hour. The mixture is cooled to -25°C and a IM solution of tert-butyldimethylsilyl triflate in dichloromethane (0.20 mol/mol of imidate) is added. After stirR1ng for 15 minutes, solid sodium hydrogen carbonate is then added and the mixture is filtered and concentrated. The residue is placed on a column of Toyopearl® HW-50 (1/1 dichloromethane/ethanol) and the fraction containing the glycosyl acceptor is returned to the reaction and then treated as above. Successive purifications are carR1ed out on a column of silica (5/4 and then 1/1 toluene/acetone) in order to obtain a fraction 73a/(3 = 7/3 (107 mg) and a fraction in 73a/P = 9/1 (201 mg) in an overall yield of 57 % (308 mg) . 'H NMR (CDCl3) 6 7.33-7.25 (m, 35H, 7Ph) , 5.65 (d, 3H, J = 3 . 5Hz, H-1 unit A, unit C and unit E), 5.57 (d, IH, J = 3.9Hz, H-1 unit G) , 5.52 (d, IH, J = 3.3Hz, H-1 unit I) , 5.2 9 (d, IH, J = 6.8Hz, H-1 unit L), 5.17 (d, IH, J = 3.5Hz, H-1 unit K), 4.56 (d, IH, J = 3.5Hz, H-1 unit M), 4.31 (d, 3H, J = 7.9Hz, H-1 unit B, unit D and unit F) , 4.27 (d, IH, J = 8.0Hz, H-1 unit H), 4.08 (d, IH, J = 8.0Hz, H-1 unit J) , 2.8O-2.50 (m, 4H, 0 (C :0) CH2CH2 (C:O) CH3) , 2.18 (s, 3H, 0(C:O)CH2CH2(C:O)CH3) , 1.97 (s, 3H, Ac) , 1.81 (s, 3H, Ac).



PREPARATION 68
Methyl [O-(2,3,6-tri-O-methyl-α-D-glucopyranosyl)-(1-4) -O- (2,3,6-tri-O-methyl-β-D-glucopyranosyl) - (1-4)] 4-O-(6-O-benzyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(benzyl 2,3-di-O-methyl-β-D-glucopyranosyluro-nate)-(1-4)-O-(3,6-di-O-acetyl-2-O-benzyl-α-D-glucopyrano-syl) - (1-4) -O- (benzyl 2, 3-di-O-methyl-α-L-idopyranosyl-uronate)-(1-4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (74).
Compound 73 (130 mg, 38.2 μmol) is treated according to Method 2 and the crude product is purified on a column of silica in order to obtain 74 (118 mg, 93 %) . [α]D + 78 (c = 0.48, dichloromethane) ; ESIMS, positive mode: monoisotopic mass = 3301.49; chemical mass = 3303.65; expeR1mental mass = 3302.40 a.m.u. 1H NMR (CDCl3) δ 7.33-7.25 (m, 35H, 7Ph) , 5.64 (d, 3H, J = 3.5Hz, H-1 unit A, unit C and unit E), 5.57 (d, IH, J = 3.9Hz, H-1 unit G) , 5.52 (d, IH, J ^ 3.3Hz, H-1 unit I), 5,29 (d, IH, J = 6.8Hz, H-1 unit L), 5.17 (d, IH, J = 3.5Hz, H-1 unit K), 4.56 (d, IH, J = 3.5Hz, H-1 unit M), 4.31 (d, 3H, J = 7.9Hz, H-1 unit B, unit D and unit F), 4.27 (d, IH, J = 8.0Hz, H-1 unit H), 4.08 (d, IH, J = 8.0Hz, H-1 unit J), 1.97 (s, 3H, Ac), 1.81 (s, 3H, Ac).
PREPARATION 69
Methyl O-(2,6-di-O-benzyl-4-O-levulinyl-3-O-methyl-α-D-glucopyrauiosyl)-(1-4)-O-(2-O-acetyl-6-O-benzyl-3-O-methyl-β-D-glucopyranosyl)-(1-4)-O-(2,6-di-O-benzyl-3-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(2-O-acetyl-6-O-benzyl-3-O-methyl-β-D-glucopyranosyl)-(1-4)-[O-(2,3,6-tri-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl)- (1-4)]^-O- (6-O-benzyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(benzyl 2,3-di-O-methyl-β-D-glucopyranosyluronate)-(1-4)-O-(3,6-di-O-acetyl-2-O-benzyl-α-D-glucopyranosyl)-(1-4)-O-(benzyl 2,3-di-O-methyl-α-L-idopyranosyluronate-(1-4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (75).

The glycosyl acceptor 74 (112 mg, 33-9 inethylmol) and the imidate 17 (59.1 mg, 37.2 inethylmol) (see Preparation 16) are dissolved in toluene (2 ml) , 4 A molecular sieves (42 mg) are added and the mixture is left stirR1ng at 25°C for 1 hour- The mixture is cooled to -20oC and a IM solution of tert-butyldimethylsilyl triflate in toluene (0,20 mol/mol of imidate) is added. After stirR1ng for 15 minutes, solid sodium hydrogen carbonate is then added and the mixture is filtered and concentrated, The residue is placed on a column of Toyopearl® HW-50 (1/1 dichloromethane/ethanol) and the fraction containing the acceptor and the 17-mer is returned to the reaction and treated as above. The product is purified successively on a column of Toyopearl, HW-50 and on a column of silica in order to obtain 75 (71 mg, 44 %) , [α] D + 80 (c = O-26, dichloromethane). ESIMS, positive mode: monoisotopic mass == 4728.10; chemical mass = 4731.26; expeR1mental mass = 4731-27 ± 0.39 a.m,u. 1H NMR (CDCl3) S of the main anomeR1c protons: 5.64; 5.57; 5,52; 5.48; 5,47; 5,29; 5.17; 4,56; 4.50; 4.29; 4.27; 4.08 ppm.



PREPARATION 70
Methyl 2,3-di-O-methyl-S-O-tert-butyldimethylsilyl-α-D-glucopyranoside (77) .
Tert-butyldimethylsilyl chloride (14.0 g, 92.9 mmol), triethylamine (15 ml, 108 mmol) and 4-dimethylaminopyridine (2G0 mg, 2.13 mmol) are added, under argon, to a solution of 76 (D. trimmell, W.M. Doane, C.R. Russel, C.E. R1st, Carbohydr. Res,, (1969) 11, 497) (15.84 g, 71.3 mmol) in dichloromethane (300 ml) . After stirR1ng for 15 hours at room temperature, the solution is diluted with dichloromethane, washed with saturated aqueous sodium hydrogen carbonate solution, dried (magnesium sulphate), filtered and concentrated. The residue is purified by flash chromatography (1.3/1 cyclohexane/ethyl acetate) in order to obtain 77 (22.79 g, 95 %) in the form of a colourless syrup, [α]+ +87 (c = 1.2, chloroform).
PREPARATION 71
Methyl 2,3-di-O-methyl-6-O-tert-butyldimethylsilyl-α-D-
xylo-4-hexulopyranoside (78).
A solution of dimethyl sulphoxide (8.7 ml, 123 mmol) in dichloromethane (20 ml) is added, under argon and at -70oC, to a solution of oxalyl chloride
(5.4 ml, 61.9 mmol) in dichloromethane (120 ml). After 15 minutes, a solution of 77 (18.78 g, 55.8 mmol) in dichloromethane is added dropwise. After magnetic stirR1ng for 15 minutes, triethylamine (37 ml, 265 mmol) is added and, after 15 minutes, the mixture is allowed to return to room temperature. Water (150 ml) is added and the aqueous phase is extracted with dichloromethane (150 ml) . The organic phases are combined, washed with saturated aqueous sodium chloride solution, dried (magnesium sulphate) and concentrated. The residue is purified by flash chromatography (9/1 and then 4/1 cyclohexane/ethyl acetate) in order to obtain 78 (17.3 g, 93 %) in the form of a colourless oil. [α]D + 98 (c = 1.0, chloroform).

PREPARATION 72
Methyl 4-deoxy-2,3-di-O-methyl-4-C-methylene-6-O-tert-
butyldimethylsilyl-α-D-xylo-hexapyranoside (79).
A 1.6 M solution of n-butyllithium in n-hexane (75 ml) is added dropwise, under argon, to a suspension of methyltriphenylphosphonium bromide (43.3 g, 127 mmol) in tetrahydrofuran (250 ml). After 30 minutes at room temperature, the mixture is cooled to -70°C. A solution of 78 (13.97 g, 41.8 mmol) in tetrahydrofuran (60 ml) is then added. After 30 minutes at -70°C, the mixture is allowed to return to room temperature. After 1 hour, saturated aqueous ammonium chloride solution (3 00 ml) is added and the aqueous phase is extracted with ether. The organic phase is dried (magnesium sulphate), filtered and concentrated. The residue is purified by flash chromatography (7/1 and then 4/1 cyclohexane/ethyl acetate) in order to obtain 79 (8,30 g, 60 %) in the form of a colourless oil, [α] D + 151 (c = 1.3, chloroform).
PREPARATION 73
Methyl 4-deoxy-2,3-di-O-methyl-4-C-methylene-α-D-xylo-
hexapyranoside (80).
Camphorsulphonic acid (pH 1) is added to a solution of 79 (8.50 g, 25.6 mmol) in a 5/1 dichloromethane/methanol mixture (250 ml) . After complete disappearance of the starting mateR1al (TLC, l/l cyclohexane/ethyl acetate), the solution is neutralized by addition of triethylamine. After concentrating, the residue is purified by flash chromatography (1/1 and then 1/2 cyclohexane/ethyl acetate) to give 80 (5.32 g, 95 %) in the form of a colourless syrup, [α]D + 239 (c = 1.0, chloroform),
PREPARATION 74
Phenyl 2,4,6-tri-O-acetyl-3-O-methyl-l-seleno-β-D-
glucopyranoside (83).
Method I: Selenophenol (5.7 ml, 53.7 mmol) is added to a solution of 81 (E.L. Hirst, E. Percival,

Methods Carbohydrate Chem, (1963) 2, 145) (l/l mixture of anomers: 13.05 g, 36.0 mmol) in dichloromethane
(120 ml) under argon. The reaction medium is cooled to 0oC and 48 % trifluoroborane diethyl etherate solution
(8.3 ml, 71.9 mmol) is added dropwise. After 3 hours at room temperature, the reaction mixture is diluted with dichloromethane (100 ml) , washed with saturated aqueous sodium hydrogen carbonate solution, dried (magnesium sulphate), filtered and concentrated. The crude compound 83 (8.17 g, 68 %) from 81) is used directly in the deacetylation reaction,
Method 2: Sodium borohydride (510 mg,
14.6 mmol) is added, at 0°C and under argon, to a
suspension of diphenyl diselenide (2.27 g, 7.27 mmol)
in ethanol. A further portion of trifluoroborane
diethyl etherate is added if the reaction medium has
not lost its oR1ginal yellow colour within 15 minutes.
This solution is transferred under argon to a solution
of 82 (A.K. Sen, K.K. Sakar, N, Banerji, J. Carjbohydr.
Chem., (1988) 7, 645) (4.22 g, 11.0 mmol) in
dichloromethane (25 ml) . After refluxing for 3 hours, the mixture is left to cool to room temperature, the sodium bromide is filtered off and the filtrate is concentrated. The residue is dissolved in dichloromethane (100 ml) and washed with aqueous IM sodium hydroxide solution (50 ml) and saturated aqueous ammonium chloride solution (50 ml). The aqueous phases are extracted with dichloromethane (20 ml) and the organic phases are dried (magnesium sulphate), filtered and concentrated. The residue is purified by flash chromatography (1.7/1 cyclohexane/ethyl acetate) and then crystallized from ethyl acetate in order to obtain 83 (4.35 g, 86 %) . m.p. 101-102°C. [α]D - 20 (c = 1.0, chloroform).
PREPARATION 75
Phenyl 3-O-methyl-l-seleno-β-D-glucopyranoside (84)•
The crude compound 83 obtained from 82 (32.3 g, 84.3 mmol) is dissolved in methanol (500 ml)

ana soaium (l. 2 g) is mt/toduced slowly. After 1 hour, the solution is neutralized by addition of IR-120 (H*) resin, filtered and concentrated. The residue is purified by flash chromatography (1.5/1/1 cyclohexane/ ethyl acetate/acetone) in order to obtain 84 in the form of a syrup (22.7 g, 81 % from 82). [α]^ - 58 (c = 1.0, methanol) .
PREPARATION 76
Phenyl 4,6-O-beiizylidene-3-O-methyl-l-seleno-β-D-gluco-
pyrazioside (85) .
P-Toluenesulphonic acid (45 mg) and benzaldehyde dimethyl acetal (5.4 ml, 3 6.0 mmol) are added, under argon, to a solution of triol 84 (7.65 g, 23.0 mmol) in acetonitrile (150 ml). After stirR1ng for 2 hours at room temperature, potassium carbonate (1.5 g) is added. After 30 minutes, the solution is filtered and then concentrated. The residue is purified by flash chromatography (3.5/1 cyclohexane/ethyl acetate) in order to obtain 85 (8.55 g, 88 %) in the form of white crystals. m.p. 123-124°C (cyclohexane/ethyl acetate), [α]D - 38 (c = 1.0, chloroform).
PREPARATION 77
Phenyl 4,6-O-benzylidene-3-O-methyl-2-O-(methyl-
4-deoxy-6-O-dimethylsilyl-2,3-di-O-methyl-4-C-
znethylene-α-D-xylo-hexopyranoside) -l-seleno-|3-D-
glucopyranoside (86).
A 1.6 M solution of n-butyllithium (7.0 ml, 11.2 mmol) is added, under argon and at -70°C, to a solution of 85 (4.30 g, 10.2 mmol) in tetrahydrofuran
(30 ml) placed in a Schlenck tube. After 10 minutes, dichlorodimethylsilane (5.0 ml, 41.2 mmol) is added and the reaction medium is warmed to room temperature. After 3 hours, the mixture is concentrated and a solution of 80 (2.10 g, 9.62 mmol) and imidazole
(985 mg, 14.4 mmol) in tetrahydrofuran (20 ml) is added. After 3 0 minutes at room temperature, the solution is concentrated, water (50 ml) is added and

the mixture is extracted with dichloromethane. The organic phase is dried (magnesium sulphate), filtered and concentrated. An analytical sample of 86 is purified by flash chromatography (2 5/1 toluene/acetone containing 0.5 % triethylamine). A colourless syrup is obtained in a yield of 90 %.
'H NMR (400MHz, C5D6) d 7.77-6.99 (m, lOH, aromatic) , 5.51 (m, IH, C:CH2) , 5.24 (m, IH, C:CH2) , 5.16 (s, IH, CHPh) , 4.85 (d, IH, J = 3.7Hz, H-1), 4.81 (d, IH, J = 9.8Hz, H-1'), 4.45 (m, IH, H-5) , 4.38 (dd, IH, J = 10.8Hz, 4.8Hz, H-6a) , 4.33 (dd, IH, J = 6.2Hz, H-6b) , 4.20 (m, IH, J = 9.2Hz, H-3), 4.05 (dd, IH, J = 10.3Hz, 4.9Hz, H-6a'), 3.87 (dd, IH, J = 8.1Hz, H-2'), 3.52, 3.38, 3.31 and 3.27 (s, 3H, OCH3) , 3.3 7 (t, IH, J = 10.3Hz, H-6b' ) , 3.3 5 (t, IH, H-4' ) , 3.32 (dd, IH, H-2) , 3.22 (dd, IH, J = 9.3Hz, H-3' ) , 3.05 (ddd, IH, J = 9.3Hz, H-5' ) , 0.3 8 and 0.37 (s, 3H, Si (CH3)2. MS (m/z) : 714 (M+NH4).
PREPARATION 78
Radical cycllzation reaction (formation of 87) and
cleavage o£ the tether (88).
A solution of tributyltin hydride (6.1 ml, 22.7 mmol) and 2,2'-azobisisobutyronitrile (200 mg, 1.22 mmol) in degassed toluene (14 ml) is added, over a peR1od of 8 hours, to a solution of crude 86 in toluene (850 ml), obtained from 85 (10.2 mmol) and 80 (9.62 mmol).
After the radical cyclization, the mixture is concentrated and the residue is dissolved in tetrahydrofuran. An excess (20 equivalents) of hydrofluoR1c acid (at a concentration of 40 % in water) is added. After complete desilylation (TLC, 4/1 toluene/acetone), the solution is neutralized by addition of solid sodium hydrogen carbonate, filtered and concentrated. The major compound 88 may be purified by crystallization, m.p. 105°C. [α] D + 119 (c = 1.1, chloroform) . 13C NMR (62.896MH2, CDCl3) d 137.29 (quarternary aromatic C) , 128.88-125.96 (aromatic C) ,

101.11 (CHPh), 9 7.64 (C-1), 83.52 (C-2), 82.76, 81.95, 80.84, 72.01, 71.92 and 64.31 (C-3, C-5, C-2' , C-3' , C-4' , C-5' ) , 75.19 (C-1' ) , 6 9.41 (C-6' ) , 62.69 (C-6) , 60.93, 60.70, 58.31 and 55.20 (OCH3) , 38.80 (C-4), 25.58 (methylene C) .
Anal. Calculated for C24H3O10H2O (502.558) :
C, 57.36/ H, 7.62. Found: C, 57.31; H, 7.54.
PREPARATION 79
Methyl 6-O-acetyl-4-C-(2-O-acetyl-4,6-O-benzylidene-3-O-methyl-α-D-glucopyranosylmethyl)-4-deoxy-2,3-di-O-methyl-α-D-glucopyranoside (89).
Compound 88 is acetylated quantitatively in a mixture of l/l acetic anhydride/pyridine, in the presence of a catalytic amount of 4-dimethylamino-pyridine. The product is obtained after concentration and chromatography, [α]D + 87 (c = 1.0, chloroform) . 'H NMR (500MHz, CDCl3) : see Table 1. 13C NMR (62.896MHz, CDCl3) d 170.81, 16 9.8 0 (C:O) , 137.18 (quartemary aromatic C), 128.92-125.95 (aromatic C), 101.31 (CHPh), 97.51 (C-1), 83.22 (C-2), 81.94, 69,25 and 63.83 (C-5, C-4', C-5'), 81.81 (C-3), 78.78 (C-3'), 72.74 (C-2') , 71.96 (C-1') , 6 9.49 (C-6') , 64.17 (C-6) , 60.64, 59.82, 58.30 and 55.19 (OCH3) , 39.00 (C-4), 26.47 (methylene C) , 20.91, 20.76 (OCOCH3) . Mass spectrum (m/z) : 586 (M+NHJ +, 569 (M+H+554 (M-OMe+NH3) +, 537 (M-OMe)+.
Anal. Calculated for C28H40O12OH20 (586,632) : C, 57.33; H, 7.22. Found: C, 57.28; H, 7.07.
The final part of the synthesis consists in converting 89 into imidate 90. To do this, the benzylidene is opened using sodium cyanoborohydride and hydrochloR1c acid. The hydroxyl group thus freed is temporaR1ly protected in the form of the p-methoxy-benzyl ether. After deacetylation, the pR1mary alcohol function is protected by selective introduction of tert-butyldimethylsilyl ether, and the compound thus obtained is methylated. Oxidation under the Jones conditions leads to the uronic acid, which is

benzylated. The p-methoxybenzyl ether is subsequently cleaved off and a levulinic ester is introduced in this position. A system using a sulphuR1c acid/acetic acid/acetic anhydride mixture leads to acetolysis of the anomeR1c methyl group as well as of the benzyl ether in position 6', and gives a mixture of two anomeR1c acetates. Selective deacetylation of position 1 is carR1ed out using hydrazine in dimethylformamide, and the mixture of anomers, dissolved in dichloro-methane, is converted into 90 with trichloroaceto-nitrile in the presence of 1,8-diazabicyclo[5.4.0]-undec-7-ene.


93
PREPARATION 80
Ethyl O- (2, 3-di-O-benzoyl-4, 6-O-benzylidene-α-D-gluco-pyranosyl) - (l->4) -2, 3, 6-tri-O-benzoyl-l-thio-β-D-glucopyranose (92)
Benzoyl chloride (24.5 ml, 211 mmol) is added dropwise over 20 minutes to a cooled (0°C) solution of compound 91 (16.7 g, 35,2 mmol) (J. Westman and M. Nilsson, J. Carbohydr. Chem., 1995, 14 (7) , 949-960) in pyridine (202 ml) . The reaction mixture is stirred for 2 0 hours at room temperature; TLC reveals an

approximately 5 0% conversion. The mixture is diluted with water and dichloromethane. After extraction, the organic phase is washed with 10% sodium hydrogen carbonate solution, water, dried over magnesium sulphate and concentrated. The residue is again treated with benzoyl chloride according to the procedure descR1bed above. The crude product is purified by chromatography on a column of silica gel to give 22 g of compound 92. TLC: Rf = 0.80, silica gel, 9/1 v/v toluene/ethanol
PREPARATION 81
O-(2,3-Di-O-benzoyl-4,6-O-ben2ylidene-α-D-glucopyranosyl)-(l->4) -O-(2, 3, 6-tri-O-benzoyl-β-D-glucopyranosyl) - (l->4) -1, 6-anhydro-2,3-di-O-methyl-β-D-glucopyranose (94)
A mixture of thioglycoside 92 (1.05 g, 1.05 mmol), compound 93 (200 mg, 1.05 mmol) (Jeanioz et al., J. Org. Chem. 1961, 26, 3939-3944) and powdered 4A molecular sieves (1.1 g) in toluene (18 ml) is stirred under a nitrogen atmosphere for 15 minutes. The mixture is then cooled to -20°C and a freshly prepared solution of N-iodosuccinimide (1.11 mmol) and trifluoromethanesulfonic acid (0.125 mmol) in 1/1 v/v dichloromethane/dioxane (6 ml) is introduced therein. After 10 minutes, the red reaction mixture is filtered, diluted with dichloromethane, extracted, washed successively with 10% sodium thiosulphate solution, 10% sodium hydrogen carbonate solution and water, dried over magnesium sulphate and then concentrated under vacuum. The residue is purified by chromatography, on a column of silica gel in order . to obtain 1.25 g of compound 94.
TLC: Rf = 0.55, silica gel, 4/6 v/v heptane/ethyl acetate

PREPARATION 82
O-(4,6-O-Benzylidene-α-D-glucopyranosyl)-(l->4) -O-(p-D-glucopyranosyl) - (l->4) -1, 6-anhydro-2/ 3-di-O-methyl-β-D-glucopyranose (95)
Potassium tert-butoxide (about 50 mg) is added to a solution of compound 94 (1.24 g, 1.11 mmol) in 1/1 v/v methanol/dioxane (7 ml) . The mixture is stirred for one hour and a further 50 mg of potassium tert-butoxide are then added; the mixture is then stirred for a further 60 minutes. The reaction mixture is neutralized with a Dowex® 50WX8 H* resin, filtered and concentrated under vacuum. After chromatography on a column of silica gel, 665 mg of compound 95 are isolated in the form of an oil.
TLC: Rf = 0.50, silica gel, 85/15 v/v dichloromethane/methanol
PREPARATION 83
O-(4,6-O-Benzylidene-2,3-di-O-methyl-α-D-glucopyranosyl) - (l-»4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (1-^4) -1, 6-anhydro-2,3-di-O-methyl-β-D-glucopyranose (96)
Sodium hydride (387 mg, 9,65 mmol) is added under a nitrogen atmosphere to a cooled (5°C) solution of compound 95 (660 mg, 1.1 mmol) in dry tetrahydrofuran (8 ml). Methyl iodide (0.51 ml, 8.22 mmol) is added dropwise and the mixture is stirred for 20 hours at room temperature. The excess sodium hydride is destroyed with methanol and the mixture is poured into 50 ml of ice-cold water. After extraction with ethyl acetate (3 times 20 ml) , the organic phase is washed with sodium chloride solution, dried over magnesium sulphate and concentrated to give 690 mg of pure compound 96.
TLC: Rf = 0.25, silica gel, 95/5 v/v dichloromethane/methanol

PREPARATION 84
O-(2,3-Di-O-methyl-α-D-glucopyranosyl)-(l-»4) -O-2,3, 6-tri-O-methyl-β-D-glucopyranosyl)- (l->4) -1,6-anhydro-2,3-di-O-lnethyl-β-D-glucopyranose (97)
The pure compound 96 (690 mg, 1.03 mmol) is dissolved in 80% acetic acid (7.3 ml) and stirred for 20 hours at 40oC. The mixture is concentrated under vacuum and co-evaporated with toluene. Chromatography on a column of silica gel in 8/1/1 dichloromethane/ethyl acetate/methanol allows 56 9 mg of compound 97 to be obtained.
TLC: Rf = 0.40, silica gel, 9/1 v/v dichlorome thane/methanol
PREPARATION 85
O-(6-O-Benzoyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(1-^4)-O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl)-(1^-4) -1,6-anhydro-2,3-di-O-methyl-β-D-glucopyranose (98)
1-Benzoyloxy-lH-benzotriazole (227 mg, 1.05 mmol) and triethylamine (1.15 mmol) are added to a solution of compound 97 (560 mg, 0.96 mmol) in dichlorome thane and the mixture is then stirred for 20 hours at room temperature. The reaction mixture is diluted with dichoromethane and washed with 10% sodium hydrogen carbonate solution and water. The organic phase is dried over magnesium sulphate, filtered and evaporated to dryness. The product is purified by chromatography on a column of silica gel in order to obtain 600 mg of compound 98-
TLC: Rf = 0.50, silica gel, 9/1 v/v dichloro-methane/methanol
PREPARATION 86
O-(2,3-Di-O-benzoyl-4,S-O-benzylidene-α-D-glucopyranosyl)-(1-^4) -O-(2, 3, 6-tri-O-benzoyl-β-D-glucopyranosyl) - (l->4) -O- (6-O-benzoyl-2, 3-di-O-methyl-α-D-glucopyranosyl)- (l->4) -O-(2, 3, S-tri-O-methyl-β-D-glucopyranosyl) - (1-^4) -1, 6-anhydro-2, 3-di-O-methyl-β-D-glucopyranose (99)

Compound 98 is converted into compound 99 according to the procedure descR1bed for the preparation of compound 94. The coupling reaction is carried out at 5°C.
TLC: Rf - 0.50, silica gel, 2/8 v/v heptane/ethyl acetate



PREPARATION 87
O-(4,6-O-Benzylidene-α-D-glucopyranosyl)-(1->4) -O- (P-D-glucopyranosyl) - (l->4) -O- (2, 3-di-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2,3,6-tri-O-niethyl-β-D-glucopyranosyl) - (l->4) -1, 6-aiihydro-2, 3-di-O-methyl-β-D-glucopyranose (100)
Compound 9 9 is converted into compound 10 0 according to the same procedure as that descR1bed for the preparation of compound 95.
TLC: Rf = 0.35, silica gel, 9/1 v/v dichloro-methane/methanol
PREPARATION 88
O- (4, 6-O-Benzylidene-2, 3-di-O-niethyl-α-D-glucopyranosyl) - (1-^4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (l->4) -O- (2,3, 6-tri-O-methyl-α-D-glucopyranosyl) - (l->'4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (l->4) -1, 6-anhydro-2, 3-di-O-methyl-β-D-glucopyranose (101)
Compound 100 is converted into compound 101 according to the same procedure as that descR1bed for the preparation of compound 96,
TLC: Rf = 0.50, silica gel, 9/1 v/v dicholoro-me thane/met hand
PREPARATION 89
O- (2,3-Di-O-methyl-α-D-glucopyranosyl) - (1^4) -O- (2,3,6-tri-O-methyl-β-D-glucopyranosyl)-(l->4) -O-(2,3,6-tri-O-methyl-α-D-glucopyranosyl) - (l-»4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (l->4) -1, 6-anhydro-2, 3-di-O-methyl-β-D-glucopyranose (102)
Compound 101 is converted into compound 102 according to the same procedure as that descR1bed for the preparation of compound 97.
TLC: Rf = 0.35, silica gel, 9/1 v/v dichloro-methane/methanol

PREPARATION 90
O-(6-O-Benzoyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(l->4)-O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl)-(1^4) -O-(2,3,6-tri-O-methyl-α-D-glucopyranosyl)- (1-^4) -O-(2,3,S-tri-O-methyl-β-D-glucopyranosyl)-(1-^4) -1,6-anhydro-2,3-di-O-methyl-β-D-glucopyranose (103)
Compound 102 is converted into compound 103 according to the same procedure as that descR1bed for the preparation of compound 98.
TLC: Rf = 0.40, silica gel, 7.0/1.5/1.5 v/v/v toluene/ethyl acetate/ethanol
PREPARATION 91
O-(2,3-Di-O-benzoyl-4,6-O-benzylidene-α-D-glucopyranosyl)- (l->4) -O-(2,3, 6-tri-O-benzoyl-β-D-glucopyranosyl) - (l->4) -O- (6-O-benzoyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(1^-4) -O-(2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (l->'4) -O- (2,3, 6-tri-O-methyl-α-D-glucopyranosyl)- (l->4) -O-(2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (l->4) -1, 6-aiihydro-2, 3-di-O-methyl-(3-D-glucopyraziose (104)
The coupling reaction of compound 103 with the disaccharide 2 is carried out according to the procedure descR1bed for the preparation of compound 99, TLC: Rf = 0.40, silica gel, 7.0/1.5/1.5 v/v/v toluene/ethyl acetate/ethanol



PREPARATION 92
O-(4,6-O-Benzylidene-α-D-glucopyranosyl)-(l->4) -O- (P-D-glucopyranosyl) - (1->4) -O- (2 , 3-di-O-methyl-α-D-glucopyranosyl)- (1^4) -O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl) - (1^4) -O- (2,3, S-tri-O-methyl-α-D-glucopyranosyl) - (1-^4) -O- (2,3, 6-tri-O-methyl-(3-D-glucopyranosyl) - (l->4) -1, 6-anhydro-2, 3-di-O-methyl-β-D-glucopyranose (105)
Compound 104 is converted into compound 105 according to the same procedure as that descR1bed for the preparation of compound 95.
TLC: Rf = 0.60, silica gel, 9/1 v/v dichloro-methane/methanol
PREPARATION 93
O-(4,6-O-Benzylidene-2,3-di-O-methyl-α-D-glucopyranosyl)- (l->4) -O-(2,3, 6-tri-O-methyl-β-D-glucopyranosyl)-(l->4) - [O-(2,3, 6-tri-O-methyl-α-D-glucopyranosyl)- (1-^4) -O-(2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (1^4) ] 2-l, 6-anhydro-2,3-di-O-methyl-β-D-glucopyranose (106)
Compound 105 is converted into compound 106 according to the same procedure as that descR1bed for the preparation of compound 96.
TLC: Rf = 0.70, silica gel, 9/1 v/v dichloro-methane/methanol
PREPARATION 94
O- (2,3-Di-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2,3,6-tri-O-methyl-β-D-glucopyranosyl) - (l->4) - [O- (2,3, 6-tri-O-methyl-α-D-glucopyratnosyl) - (l->4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyrauiosyl) - (l->4) ] j-l/ 6-anhydro-2/ 3-di-O-methyl-β-D-glucopyranose (107)
A solution of compound 106 (5.05 g, 2.0 mmol) in 8 0% acetic acid (50 ml) is stirred for 2 0 hours at 40°C. The mixture is concentrated under vacuum and co-evaporated with toluene. The residue is dissolved in ethyl acetate and extracted with water The aqueous phase is extracted with dichloromethane and the organic

phase is dried over magnesium sulphate, tiltered and evaporated to dryness to give 2.68 g of compound 107. TLC: Rf = 0.50, silica gel, 9/1 v/v dichloro-methane/methanol
PREPARATION 95
O-(6-O-Benzoyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(l->4)-O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl)-(1-^4) -[O-(2,3,S-tri-O-methyl-α-D-glucopyranosyl)- (l->4) -O-(2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (1-^4) ] ^-l/ 6-aiihydro-2,3-di-O-methyl-β-D-glucopyranose (108)
Compound 107 is converted into compound 108 according to the same procedure as that descR1bed for the preparation of compound 98.
TLC: Rf = 0,80, silica gel, 7.0/1.5/1.5 v/v/v toluene/ethyl acetate/ethanol
PREPARATION 96
O- (2, 3-Di-O-benzoyl-4, S-G-benzylidene-α-D-glucopyranosyl) - (l->4) -O- (2, 3, 6-tri-O-benzoyl-β-D-glucopyranosyl)-(1,4)-O-(6-O-benzoyl-2,3-di-O-methyl-α-D-glucopyrauiosyl) - (1^4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyranosyl)-(l->4) - [O-(2, 3, 6-tri-O-methyl-α-D-glucopyranosyl) - (1^4) -O- (2,3, 6-tri-O-methyl-(3-D-glucopyranosyl) - (l->4) ] ]2-l, 6-aiihydro-2, 3-di-O-methyl-β-D-glucopyranose (109)
A mixture of the thioglycoside 92 (1.97 g, 2.0 mmol, 3.5 eq), heptasaccharide 108 (0.86 g, 0.57 mmol) and powdered 4A molecular sieves in toluene (22 ml) is stirred under a nitrogen atmosphere for 15 minutes. A freshly prepared solution containing N-iodosuccinimide (496 mg, 2.2 mmol) and trifluoro-methanesulphonic acid (0.808 mmol) in 1/1 v/v dichloro-methane/dioxane (12 ml) is then added dropwise at room temperature. After 10 minutes, the reaction mixture is filtered, diluted with dichloromethane, extracted, washed with 10% sodium thiosulphate solution and with 10% sodium hydrogen carbonate solution, dried over magnesium sulphate and concentrated under vacuum. The

crude product is purified by chromatography on a column of silica gel, to give 1.09 g of compound 109. TLC: Rf = 0.80, silica gel, 6/2/2 v/v/v toluene/ethyl acetate/ethanol



PREPARATION 97
O-(4,6-O-Benzylidene-α-D-glucopyranosyl)-(1^4) -O-(P-D-glucopyranosyl)- (1^4) -O-(2,3,-di-O-methyl-α-D-glucopyranosyl)- (l->4) -O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl)-[(1-4)-O-(2,3,6-tri-O-methyl-α-D-glucopyranosyl)- (1^4) -O-(2,3,S-tri-O-methyl-β-D-glucopyranosyl) ] j- (l->4) -1, 6-anhydro-2, 3-di-O-methyl-β-D-glucopyranose (110)
Compound 109 is converted into compound 110 according to the same procedure as that descR1bed for the preparation of compound 95.
TLC: Rf = 0.25, silica gel, 5,0/2.5/2.5 v/v/v toluene/ethyl acetate/ethanol
PREPARATION 98
O- (4, 6-O-Beii2ylidene-2, 3-di-O-methyl-α-D-glucopyranosyl)- (l->4) -O-(2,3, S-tri-O-methyl-β-D-glucopyranosyl)-(l->4) - [O-(2, 3, 6-tri-O-methyl-α-D-glucopyranosyl)-(l->4) -O-(2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (l->4) ] 3-I, 6-anhydro-2, 3-di-O-methyl-β-D-glucopyranose (111)
Compound 110 is converted into compound 111 according to the same procedure as that descR1bed for the preparation of compound 96,
TLC: Rf = 0.50, silica gel, 6/2/2 v/v/v toluene/ethyl acetate/ethanol
PREPARATION 99
O- (2,3-Di-O-methyl-α-D-glucopyranosyl) - (1^4) -O- (2,3,6-tri-O-methyl-β-D-glucopyranosyl)- (1-^4) -[O-(2,3,6-tri-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (l->4) ] 3-I, 6-aiihydro-2, 3-di-O-methyl-β-D-glucopyranose (112)
Compound 111 is converted into compound 112 according to the same procedure as that descR1bed for the preparation of compound 97.
TLC: Rf = 0.20, silica gel, 6/2/2 v/v/v toluene/ethyl acetate/ethanol

PREPARATION 100
O-(6-O-Benzoyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(l->4)-O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl)-(l->4) -[O-(2,3,6-tri-O-methyl-α-D-glucopyranosyl)-(l->4) -O-(2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (l->4) ] 3-I, 5-
anhydro-2,3-di-O-methyl-β-D-glucopyranose (113)
Compound 112 is converted into compound 113
according to the same procedure as that descR1bed for
the preparation of compound 98.
TLC: Rf = 0.20, silica gel, 6/2/2 v/v/v toluene/ethyl
acetate/ethanol
PREPARATION 101
O-(6-O-Benzoyl-4-O-levulinyl-2,3-di-O-methyl-α-D-glucopyranosyl) - (l->'4) -O- (2,3, 6-tri-O-methyl-(3-D-glucopyranosyl) - (l->4) - [O- (2,3, 6-tri-O-methyl-α-D-glucopyranosyl) - (l->'4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (l->'4) ] 3-I, 6-aiihydro-2, 3-di-O-methyl-β-D-glucopyranose (114)
1-{3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (48 mg, 0.25 mmol), levulinic acid (29 mg, 0.25 mmol) and dimethylaminopyridine (4 mg, 0.033 mmol) are added to a solution of compound 113 (320 mg, 0.167 mmol) in dioxane (1 ml). The reaction mixture is stirred for 3 hours at room temperature under a nitrogen atmosphere. Dichloromethane and water are then added and, after extraction, the organic phase is washed with water, dried over magnesium sulphate, filtered and concentrated. The crude product is purified by chromatography on a column of silica gel to give 312 mg of compound 114.
TLC: Rf = 0.50, silica gel, 6/2/2 v/v/v toluene/ethyl acetate/ethanol
PREPARATION 102
O- (6-O-Benzoyl-4-O-leviilinyl-2, 3-di-O-methyl-α-D-glucopyranosyl)- (1-^4) -O-(2,3, 6-tri-O-methyl-β-D-glucopyranosyl)-(1^4) - [O-(2,3, 6-tri-O-methyl-α-D-glucopyranosyl) - (1">^4) -O- (2,3, S-tri-O-methyl-β-D-

glucopyranosyl) - (l->4) ] 3-I, 6-di-O-acetyI-2 , 3-di-O-methyl-a,p-D-glucopyranose (115)
A solution of compound 114 (312 mg, 0.155 mmol) in a mixture of acetic anhydride (2.25 ml), acetic acid (50 μl) and trif luoroacetic acid (0.14 ml) is stirred for 4 hours at room temperature. After addition of toluene (10 ml), the mixture is concentrated and co-evaporated with toluene (3 times 10 ml). After chromatography on a column of silica gel, 324 mg of compound 115 are isolated.
TLC: Rf = 0,65, silica gel, 6/2/2 v/v/v toluene/ethyl acetate/ethanol

SCHEME 27 - Synthesis of the oligosaccharide 117

A solution of compound 115 (324 mg, 0.153 mmol) and morpholine (22.3 μ1, 0.256 mmol) in toluene (2 ml) is stirred for 4 hours at 35oC. Morpholine (22.3 μ1) is then added again and the reaction mixture is stirred for 2 0 hours at 3 5 ° C. The mixture is cooled rapidly with water. After extraction with dichloromethane, the organic phase is washed successively with 0.IN hydrochloR1c acid and water, dried and evaporated to dryness. After chromatography on a column of silica gel, 280 mg of compound 116 are isolated. TLC: Rf = 0.45, silica gel, 6/2/2 v/v/v toluene/ethyl acetate/ethanol
PREPARATION 104
O-(6-O-Benzoyl-4-O-levulinyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(l->4) -O-(2,3, S-tri-O-methyl-β-D-glucopyranosyl)-(l->4) - [O-(2,3, 6-tri-O-methyl-α-D-glucopyranosyl)-(1-^4) -O-(2,3,6-tri-O-methyl-β-D-

glucopyranosyl) - (1-^4) ] 3-6-O-acetyl-2, 3-di-O-methyl-a, P-D-glucopyranose trichloroacetimidate(117)
trichloroacetonitrile (39μ1, 0.39 mmol) and caesium carbonate (4.7 mg) are added to a solution of compound 116 (138 mg, 0.066 mmol) in dichloromethane (1.5 ml). After stirR1ng for 2 hours, the mixture is filtered and concentrated and the residue is chromatographed on a column of silica gel to give 152 mg of the imidate 117.
TLC: Rf = 0.35, silica gel, 8/1/1 v/v/v toluene/ethyl acetate/ethanol



PREPARATION 105
Methyl 2-O-benzyl-4,6-O-benzylidene-α-D-glucopyranoside (119)
The compound 118 (60 g) (commercially available) is dissolved in dimethylformamide (858 ml) with benzyl bromide (50.5 ml). After cooling to 10°C, aqueous 20% sodium hydroxide solution is added dropwise. After stirR1ng for 1 hour, the temperature is raised to 20°C and the mixture is stirred for a further 20 hours. The solution is then poured into a mixture of ice-water and toluene and extracted. The organic phase is concentrated and the crude product is purified by crystallization to give 30.0 g of compound 119. TLC: Rf = 0.60, silica gel, 7/3 v/v toluene/ethyl acetate
PREPARATION 106
Methyl 2-O-benzyl-4,6-O-benzylidene-3-O-β-methoxy-
benzyl-α-D-glucopyranoside (120)
Compound 119 (26.4 g) is dissolved in dimethylf ormamide (211 ml) and cooled to 5®C. Sodium hydride (2.5 g) is added under a nitrogen atmosphere. 4-methoxybenzyle chloride (13.3 g) is then added dropwise and the mixture is stirred for 1 hour at room temperature. The mixture is diluted with ethyl acetate, washed twice with water and concentrated to give 4 0.7 g of pure compound 120.
TLC: Rf = 0.80, silica gel, 7/3 v/v toluene/ethyl acetate
PREPARATION 107
Methyl 2-O-benzyl-3-O-β-inethoxybenzyl-α-D-gluco-
pyranoside (121)
Compound 120 (34.9 g) is dissolved in aqueous 60% acetic acid and stirred for 4 hours at 60oC. The mixture is diluted with toluene and concentrated. Purification by chromatography on a column of silica gel allows 26.4 g of compound 121 to be obtained.

TLC: Rf = 0.07, silica gel, 7/3 v/v toluene/ethyl acetate
PREPARATION 108
Methyl 2-O-benzyl-3-O-β-methoxybenzyl-6-O-methyl-α-D-
glucopyranoside (122)
Compound 121 (26.4 g) is dissolved in dichloromethane (263 ml) under a nitrogen atmosphere. trimethyloxonium tetrafluoroborate (11.6 g) and 2,6-di-tert-butyl-4-methylpyridine (17.4 g) are added at room temperature. After 4 hours, the mixture is poured onto ice-water and extracted with dichloromethane. The organic phase is washed with sodium hydrogen carbonate and concentrated. Purification of the crude product by chromatography on a column of silica gel allows 18.5 g of compound 122 to be obtained.
TLC: Rf = 0.25, silica gel, 7/3 v/v toluene/ethyl acetate
PREPARATION 109
Ethyl 2,4,6-tri-O-acetyl-3-O-methyl-l-thio-α-L-
idopyranose (124)
Compound 123 (1,2,4,6-tetrα-O-acetyl-3-O-methyl-α-L-idopyranose) (Jaurand et al. Bio. Med. Chem. Lett. 19 92, 2, 8 97-900) (48.4 g) is dissolved in toluene (175 ml). Ethanethiol (20 ml) and boron trifluoride etherate in toluene (134 ml) are added, under a nitrogen atmosphere. After stirR1ng for 1 hour, aqueous sodium hydrogen carbonate (400 ml) is added and the mixture is stirred for a further one hour. The mixture is then poured into ethyl acetate. The organic phase is washed twice with water and concentrated. Purification by chromatography on a column of silica gel allows 2 9.6 g of compound 124 to be obtained. TLC: Rf = 0.45, silica gel, 6/4 v/v toluene/ethyl acetate

PREPARATION 110
Methyl O-(2,4,6-tri-O-acetyl-3-O-methyl-α-L-
idopyranosyl- (l->4) -2-O-benzyl-3-O-β-inethoxybenzyl-6-O-methyl-α-D-glucopyranoside (125)
Compound 122 (17.5 g) and compound 124 (28.2 g) are dissolved in toluene (525 ml) under a nitrogen atmosphere. After adding 4A molecular sieves, the reaction is cooled to -20®C. A freshly prepared solution of 0. IM N-iodosuccinimide (17.4 g) and trifluoromethanesulphonic acid (1.38 ml) in 1/1 v/v dioxane/dichloromethane is added dropwise under a continuous flow of nitrogen. After 10 minutes, the red reaction mixture is filtered and washed successively with aqueous sodium thiosulphate and aqueous sodium hydrogen carbonate. The organic phase is concentrated under vacuum and 30.0 g of compound 125 are isolated. TLC: Rf = 0.45, silica gel, 8/2 v/v dichloro-methane/ethyl acetate
PREPARATION 111
Methyl O- O-O-methyl-α-L-idopyranosyl) - (l->'4) -2-O-
benzyl-3-O-β-methoxybenzyl-6-O-methyl-α-D-
glucopyranoside (126)
Compound 125 (30.0 g) is dissolved in 460 ml of 1/1 v/v methanol/dioxane and potassium tert-butoxide is added. After 15 minutes, the mixture is neutralized with a Dowex 50WX8H+ resin and concentrated under vacuum. Purification is carried out by chromatography on a column of silica gel to give 17.4 g of compound 126.
TLC: Rf = 0.25, silica gel, 95/5 v/v dichloro-methane/methanol
PREPARATION 112
Methyl O-(4,6-O-isopropylidene-3-O-methyl-α-L-
idopyranosyl) - (l->4) -2-O-benzyl-3-O-β-inethoxybenzyl-6-O-methyl-α-D-glucopyranoside (127)
Compound 126 (17.4 g) is dissolved in dimethylformamide (77 ml) under a nitrogen atmosphere.

2,2-Dimethoxypropane {26 ml) and p-toluenesulphonic acid are added and the mixture is then stirred for 3 0 minutes. Dilution of the mixture with aqueous sodium hydrogen carbonate followed by its extraction with ethyl acetate allows 19.7 g of compound 127 to be obtained after evaporation of the solvent. TLC: Rf = 0.45, silica gel, 95/5 v/v dichloromethane/methanol
PREPARATION 113
Methyl O- (4/ 6-O-isopropylidene-2, 3-di-O-methyl-α-L-idopyranosyl) - (l->4) -2-O-benzyl-3-O-inethoxybenzyl-6-O-methyl-α-D-glucopyranoside (128)
Compound 127 (18.5 g) is dissolved in dimethylformamide (24.4 ml) and cooled to 0°C. Sodium hydride (1.47 g; 60% dispersion in oil) and iodomethane (2.36 ml) are added under a nitrogen atmosphere. After one hour, the excess sodium hydride is destroyed with methanol and the mixture is extracted with dichloromethane and concentrated to give 20.0 g of compound 128.
TLC: Rf = 0.85, silica gel, 95/5 v/v dichloro-methane/methanol



PREPARATION 114
Methyl O-(4,6-O-isopropylidene-2,3-di-O-methyl-α-L-ido-pyranosyl) - (l->4) -2-O-benzyl-6-O-methyl-α-D-glucopyranoside (12 9)
Compound 128 (18.4 g) is dissolved in dichloromethane (838 ml) and water (168 ml) . 2,3-Dichloro-5,6-dicyano-l,4-benzoquinone (7.1 g) is added and the mixture is stirred for 18 hours at A^C. The mixture is poured into aqueous sodium hydrogen carbonate and extracted with dichloromethane. Concentration of the organic phase gives 12.7 g of compound 129.
TLC: Rf = 0.40, silica gel, 95/5 v/v dichloromethane/methanol
PREPARATION 115
Methyl O-(4,6-O-isopropylidene-2,3-di-O-methyl-α-L-ido-pyranosyl) - (l->4) -2,3-di-O-benzyl-6-O-methyl-α-D-glucopyranoside (130)
Compound 129 (10.5 g) is dissolved in dry dimethylformamide (178 ml) and then cooled to 0°C under a nitrogen atmosphere. Sodium hydride (1.91 g; 60% dispersion in oil) is added, followed by dropwise addition of benzyl bromide (3.3 ml). After 30 minutes, the reaction is complete and the excess sodium hydride is destroyed with methanol. Water is added and the mixture is extracted twice with ethyl acetate. Evaporation of the solvent allows 13.6 g of compound 130 to be obtained.
TLC: Rf = 0.50, silica gel, 1/1 v/v toluene/ethyl acetate
PREPARATION 116
Methyl O-(2,3-di-O-methyl-α-L-idopyranosyl)-(l->4) -2,3-
di-O-benzyl-S-O-methyl-α-D-glucopyranoside (131)
Compound 130 is dissolved in 77/33 (v/v) acetic acid/water and stirred overnight. The mixture is co-evaporated twice with toluene and purified by

chromatography on a column of silica gel to obram
11.5 g of compound 131.
TLC: Rf = 0.09, silica gel, 1/1 v/v toluene/ethyl
acetate
Rf = 0.68, silica gel, 9/1 v/v
dichloromethane/methanol
PREPARATION 117
Methyl O-(2,3-di-O-methYl-α-L-idopyranosyluronic acid)-
(1^'4)-2,3-di-O-benzyl-6-O-methyl-α-D-glucopyranoside
(132)
Free radical 2,2,6,6-tetramethyl-l-piperidinyloxy(33 mg) , sodium hydrogen carbonate solution (40 ml) , potassium bromide (218 mg) and tetrabutylammonium chloride (289 mg) are added to a solution of compound 131 (11.6 g) in dichloromethane (60 ml) • The mixture is cooled to 0oC and a mixture of saturated sodium chloride solution (44 ml), saturated sodium hydrogen carbonate solution (21.8 ml) and sodium hypochloR1te (1.3 M, 50 ml) is added over 15 minutes. After stirR1ng for 1 hour, the mixture is diluted with water and extracted (3 times) with dichloromethane. The organic phase is washed with aqueous sodium chloride solution, dried over magnesium sulphate, filtered and evaporated to dryness to give 13.4 g of the crude compound 132,
TLC: Rf = 0.14, silica gel, 9/1 v/v dichloromethane/methanol
PREPARATION 118
Methyl O-(benzyl 2,3-di-O-methyl-α-L-idopyrano-syluronate) - (l->4) -2 ,3-di-O-benzyl-6-O-methyl-α-D-glucopyranoside (133)
Compound 132 is dissolved in dimethylformamide (110 ml) under a nitrogen atmosphere. Potassium :iydrogen carbonate (5.7 g) and benzyl bromide (10.7 ml) are added and the mixture is stirred for 90 minutes. i:thyl acetate and water are added and, after extraction, the organic phase is concentrated.

Purification by chromatography on a column oz silica
gel allows 9.9 g of compound 133 to be obtained.
TLC: Rf = 0.43, silica gel, 4/6 v/v toluene/ethyl
acetate
PREPARATION 119
Methyl O-(benzyl 2,3-di-O-methyl-β-D-
glucopyranosyluronate)- (l->4) -2, 3-di-O-benzyl-6-O-methyl-α-D-glucopyranoside (134)
Compound 133 (9.9 g) is dissolved in 300 ml of methanol and heated to reflux under a nitrogen atmosphere. A IM solution of sodium methoxide in methanol (65.2 ml) is added dropwise and the mixture is stirred and heated at reflux for 3 hours. The mixture is then cooled to room temperature, IN sodium hydroxide (22.2 ml) is added and the reaction mixture is stirred for a further 90 minutes. After neutralization with Dowex 50WX8H* resin and filtration, the mixture is concentrated. The pure product is dissolved in dimethylformamide (192 ml) and molecular sieves are added under a nitrogen atmosphere. Potassium hydrogen carbonate (3.2 g) and benzyl bromide (4.8 ml) are added and the mixture is stirred for 5 hours. After addition of ethyl acetate and water, extraction and separation of the two phases, the organic phase is concentrated. The crude product is purified by chromatography on a column of silica gel to give 6.19 g of compound 134 and 1.88 g of the starting compound 133.
TLC: Rf = 0.55, silica gel, 4/6 v/v toluene/ethyl acetate
PREPARATION 120
Methyl O-(benzyl 4-O-levulinyl-2, 3-di-O-methyl-β-D-glucopyranosyluronate) - (1^4) -2,3-di-O-benzyl-6-O-methyl-α-D-glucopyranoside (135)
Compound 134 (6,2 g) is dissolved in 40 ml of
dioxane. Levulinic acid (2.1 g) , dicyclo-
hexylcarbodiimide (3.75 g) and 4-dimethylaminopyridine
(0.2 g) are added and the mixture is stirred for

2 hours under a nitrogen atmosphere. Diethyl ether (95 ml) is added and the precipitate is filtered off. The filtrate is washed with aqueous potassium hydrogen sulphate, dried over magnesium sulphate, filtered and concentrated. Crystallization from ether/heptane allows 6.2 g of compound 135 to be obtained.
TLC: Rf = 0.26, silica gel, 95/5 v/v dichloromethane/acetone
PREPARATION 121
O-(Benzyl 4-O-levulinyl-2,3-di-O-methyl-β-D-gluco-pyranosyluronate) - (l->4) -1, 3-di-O-acetyl-2-O-benzyl-6-O-methyl-a,p-D-glucopyranos8 (136)
Compound 135 (6.1 g) is dissolved in acetic anhydride (256 ml) under a nitrogen atmosphere and cooled to -20°C. A mixture of sulphuR1c acid (4.9 ml) in acetic anhydride (4 9 ml) is added dropwise over 3 0 minutes. After 60 minutes, sodium acetate is added until a mixture having a neutral pH is obtained. Ethyl acetate and water are then added and the organic phase is concentrated. Purification by chromatography on a column of silica gel allows 4.2 g of compound 136 to be obtained.
TLC: Rf = 0.24, silica gel, 8/2 v/v dichloromethane/ethyl acetate
PREPARATION 122
O-(Benzyl 4-O-levulinyl-2,3-di-O-methyl-β-D-gluco-pyranosyluronate) - (l->'4) -3-O-acetyl-2-O-benzyl-6-O-methyl-a,p-D-glucopyranose (137)
Compound 136 (4.2 g) is dissolved in tetrahydrofuran (42 ml) and piperidine (4.1 ml) is added. The mixture is stirred overnight at room temperature. Ethyl acetate is added and the mixture is washed with 0.5 N hydrochloR1c acid. The organic phase is concentrated and the residue is purified by chromatography on a column of silica gel to give 3.2 g of compound 137.

TLC; Rf = 0.33, silica gel, 1/1 v/v
dichloromethane/ethyl acetate
PREPARATION 123
O- (Benzyl 4-O-levulinyl-2 , 3-di-O-methyl-α-D-
glucopyranosyluronate) - (l->4) -3-O-acetyl-2-O-beiizyl-6-O-methyl-α-D-glucopyranose trichloroacetimidate (13 8)
Compound 137 (1.59 g) is dissolved in dry dichloromethane under a nitrogen atmosphere. trichloroacetonitrile (1.1 ml) and caesium carbonate (72 mg) are added and the mixture is stirred for 1 hour. The caesium carbonate is filtered off and the filtrate is concentrated- Purification by chromatography on a column of silica gel allows 1.57 g of compound 13 8 to be obtained.
TLC: Rf = 0.60, silica gel, 3/7 v/v toluene/ethyl acetate

PREPARATION 124
Methyl O- (benzyl 4-O-levulinyl-2,3-di-O-methyl-β-D-
glucopyranosyluronate) - (1→4) -O- (3-O-acetyl-2-0-benzyl-

6-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (benzyl 2,3-di-O-methyl-α-L-idopyranosyluronate)-(l->4) -2 , 3-di-O-benzyl-6-O-methyl-α-D-glucopyranoside (13 9)
A mixture of compound 133 (300 mg) and compound 138 (455.6 mg) is co-evaporated with toluene and dissolved in dichloromethane (6 ml) under a nitrogen atmosphere, After addition of 4A molecular sieves, the mixture is cooled to -20'='0. After stirR1ng for 2 0 minutes, trimethylsilyl trifluoromethanesulphonate (15 mol% relative to compound 138) is added. After 10 minutes, the mixture is quenched with aqueous sodium hydrogen carbonate. After filtration of the molecular sieves, the filtrate is diluted with dichloromethane, washed with water, concentrated and purified by chromatography on a column of silica gel to give 560 mg of compound 13 9,
TLC: Rf = 0.50, silica gel, 3/7 v/v toluene/ethyl acetate
PREPARATION 125
Methyl O-(benzyl 2,3-di-O-methyl-β-D-
glucopyranosyluronate) - (1^-4) -O- (3-O-acetyl-2-O-benzyl-6-O-methyl-α-D-glucopyranosyl) - (1—►4) -O- (benzyl 2, 3-di-O-methyl-α-L-idopyranosyluronate) - (l->4) -2,3-di-O-benzyl-6-O-methyl-α-D-glucopyrsaxoside (140)
Compound 139 (532.6 mg) is dissolved in pyridine (1.9 ml) and a mixture of acetic acid (2.4 ml) and hydrazine hydrate (0.3 ml) in pyridine (1.9 ml) is added at room temperature. After stirR1ng for 9 minutes, dichloromethane and water are added. The organic phase is separated out and washed successively with 0.1 N hydrochloR1c acid, aqueous sodium hydrogen carbonate and water. The organic phase is concentrated and purified by chromatography on a column of silica gel to give 451 mg of compound 140.
TLC: Rf = 0.45, silica gel, 3/7 v/v toluene/ethyl acetate



PREPARATION 12 6
Methyl O-(6-O-benzoyl-4-O-levulinyl-2,3-di-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyranosyl)- (l->4) - [O-(2,3, 6-tri-O-methyl-α-D-glucopyranosyl)- (1^4) -O-(2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (l->4) ] 3-O- (6-O-acetyl-2, 3-di-O-methyl-α-D-glucopyranosyl) - (l->'4) -O- (benzyl 2, 3-di-O-methyl-β-D-glucopyranosyluronate)- (1->4) -O-(3-O-acetyl-2-O-benzyl-6-O-methyl-α-D-glucopyranosyl) - (1-^4) -O- (benzyl 2, 3-di-O-methyl-α-L-idopyranosyluronate) - (l->4) -2, 3-di-O-benzyl-6-O-methyl-α-D-glucopyranoside (141)
A mixture of compound 117 (144 mg, 0.064 mmol) and compound 140 (76 g, 0,058 mmol) is co-evaporated with toluene and dissolved in 1/2 v/v dichloromethane/diethyl ether (3.0 ml). 4A molecular sieves (140 mg) are added under a nitrogen atmosphere and the mixture is cooled to 0°C. Tert-butyldimethylsilyl trifluoromethanesulphonate (128 |il of a 0.1 molar solution in dichloromethane) is added and, after 15 minutes, the mixture is quenched with sodium hydrogen carbonate solution. After extraction with water and dichloromethane, the organic phase is dried and concentrated. The product is first purified by chromatography on Sephadex LH 20 (1/1 v/v lichloromethane/methanol) and then by chromatography on a column of silica gel, to give 124 mg of compound 141 in an a/p ratio of 8/2. TLC: Rf = 0.60, silica gel, 1/1 v/v toluene/acetone
PREPARATION 127
4ethyl O- (6-O-benzoyl-2, 3-di-O-methyl-α-D-
glucopyranosyl) - (1-^4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (l->4) - [O- (2,3, 6-tri-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2, 3, S-tri-O-methyl-β-D-glucopyranosyl) - (1^4) ] 3-O- (6-O-acetyl-2, 3-di-O-methyl-x-D-glucopyranosyl)-(l->4) -O- (benzyl 2,3-di-O-methyl-β-p-glucopyranosyluronate) - (l->4) -O- (3-O-acetyl-2-O-benzyl-6-O-methyl-α-D-glucopyranosyl) - (1-^4) -O- (benzyl

2 , 3 -di-O-methyl-α-L-idopyranosyluronate) - (l->4) -2 , 3-di-O-benzyl-S-O-methyl-α-D-glucopyranoside (142)
Compound 141 is converted into compound 142 according to the procedure descR1bed for the preparation of compound 140.
Compound 142 is isolated as an 8/2 a/p mixture. TLC: Rf = 0.45, silica gel, 1/1 v/v toluene/acetone



PREPARATION 12 8
O- (2,3,4,6-Tetra-O-acetyl-α-D-glucopyranosyl)-(1^4) -O-(2,3,6-tri-O-acetyl-α-D-glucopyranosyl)-(1→4) -1,2,3,6-tetrα-O-acetyl-β-D-glucopyranose (144)
Maltotriose (7 g, 13.9 mmol) (commercially available) is added portionwise to a suspension of sodium acetate (7 g, 8 5 mmol) in acetic anhydride (70 ml) at 155'=*C. After 15 minutes, the clear solution is cooled and quenched with ice-water (700 ml) . After extraction with ethyl acetate, the organic phase is washed with water, dried over magnesium sulphate, filtered and concentrated to give 13.1 g of compound 144.
TLC: Rf = 0.53, silica gel, 7/3 v/v dichloromethane/ethyl acetate
PREPARATION 129
Ethyl O-(2,3,4,6-tetrα-O-acetyl-α-D-glucopyranosyl)-(l->4) -O- (2,3, 6-tri-O-acetyl-α-D-glucopyranosyl) - (1→-4) -2,3,6-tri-O-acetyl-l-thio-β-D-glucopyranoside (145)
Compound 144 (13 g, 13.5 mmol) is dissolved in toluene (80 ml). Ethanethiol (1.97 ml, 26.9 mmol) and boron trifluoride diethyl etherate (13.7 ml of a one molar solution in toluene) is added under a nitrogen atmosphere. After stirR1ng for 60 hours, the mixture is diluted with water and dichloromethane. After extraction, the organic phase is washed with 10% sodium hydrogen carbonate solution and water, dried, filtered and concentrated. The crude product is purified by chromatography on a column of silica gel to give 8.6 g of compound 145.
TLC: Rf = 0,60, silica gel, 7/3 v/v dichloromethane/ethyl acetate
PREPARATION 130
Ethyl O-(α-D-glucopyranosyl)- (l->4)-O-(α-D-
glucopyranosyl) - (l->4) -1-thio-β-D-glucopyranoside (146)

Compound 145 is converted into compound 146 according to the procedure descR1bed for the preparation of compound 95.
TLC: Rf = 0.80, silica gel, 13/7/1.6/4 v/v/v/v ethyl acetate/pyridine/acetic acid/water
PREPARATION 131
Ethyl O- (2,3,4,6-tetra-O-benzoyl-α-D-glucopyranosyl)-(l-»4)-O-(2,3,6-tri-O-benzoyl-α-D-glucopyranosyl)-(1^4)-2,3,6-tri-O-benzoyl-l-thio-β-D-glucopyranoside (147)
Compound 146 is converted into compound 147
according to the procedure descR1bed for the
preparation of compound 92.
TLC: Rf = 0.50, silica gel, 9/1 v/v toluene/ethyl
acetate



PREPARATION 132
Methyl O-(2,3,4,6-tetra-O-benzoyl-α-D-glucopyranosyl)-(1-^4)-O-(2,3,6-tri-O-benzoyl-α-D-glucopyranosyl)-(1^4)-O- (2,3,6-tri-O-benzoyl-β-D-glucopyranosyl)-(l->4)-O-(6-O-benzoyl-2,3-di-O-methyl-α-D-glucopyranosyl)- (1^4) -O-(2,3, 6-tri-O-methyl-β-D-glucopyranosyl)- (l->4) - [O-(2,3, 6-tri-O-methyl-α-D-glucopyranosyl)- (1^'4) -O-(2,3, 6-tri-O-methyl-β-D-glucopyranosyl)-(l->4) ] 3-O-(6-O-acetyl-2,3-di-O-methyl-α-D-glucopyranosyl) - (1->4) -O- (benzyl 2, 3-di-O-methyl-β-D-glucopyranosyluronate) - (1→4) -O- (3-O-acetyl-2-O-benzyl-6-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (benzyl 2,3-di-O-methyl-α-L-idopyranosyluronate) - (1-^4) -2, S-di-O-benzyl-S-O-methyl-α-D-glucopyranoside (148)
The thioglycoside 147 (105 mg, 0.066 mmol) and the acceptor 142 (55 mg, 0.017 mmol), (α/β of 8/2) are coupled according to the procedure descR1bed for compound 109. The product is first purified by chromatography on Sephadex LH 20 (1/1 dichloro-methane/methanol) and then by chromatography on a column of silica gel (9/0.5/0.5 v/v/v diethyl ether/ethyl acetate/ethanol) to give 49 mg of compound 148.
TLC: Rf = 0.30, silica gel, 85/7.5/7.5 v/v/v diethyl ether/ethyl acetate/ethanol
PREPARATION 133
Methyl O-(2,3,4,6-tetrα-O-benzoyl-α-D-glucopyranosyl)-(l->4)-O- (2,3,6-tri-O-benzoyl-α-D-glucopyranosyl)-(l->4)-O-(2,3,6-tri-O-benzoyl-β-D-glucopyranosyl)-(l->4)-O-(6-O-benzoyl-2,3-di-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (l->4) - [O- (2,3, 6-tri-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (1^^4) ] 3-O- (6-O-acetyl-2, 3-di-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2, 3-di-O-methyl-β-D-glucopyranosyluronic acid) - (1-^4)-O-(3-O-acetyl-6-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2, 3-di-O-methyl-α-

L-idopyranosyluronic acid) - (1→ 4)- 6-O-methyl-α ~ D- glucopyranoside (149)
A solution of compound 148 (47mg, 0.01 mmol) in ethyl acetate (10 ml) is stirred under a hydrogen atmosphere in the presence of 10 palladium-on charcoal (90 w/w relative to compound 148) for 3 hours and filtered. The filtrate is concentrated to give 42 mg of compound 149. TLC: Rf = 0.35, silica gel, 20/7/1-6/4 v/v/v/v ethyl acetate/pyridine/acetic acid/water
PREPARATION 134
Methyl O-(α-D-glucopyranosyl)-(l->4) -O-(α-D-
glucopyranosyl)- (l->4)-O-(p-D-glucopyranosyl)- (1-^4)-O-(2 ,3-di-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2,3,6-tri-O-methyl-β-D-rglucopyranosyl) - (l->4) - [O- (2,3, 6-tri-O-mathyl-α-D-gluGOpyranosyl) -(l->4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyranosyl) -(l->4) ]3-O-(2,3-di-O-methYl-α-D-glucopyranosyl) - (l'->4) -O-(2,3-di-O-methyl-β-D-glucopyranosyluronic acid) - (l->4) -O- (6-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2 ,3-di-O-methyl-α-L-idopyranosyluronic acid) - (l->4) -6-O-methyl-α-β-gluco-pyranosidd (150)
A mixture of methanol (0,22 ml) and 0.65 N sodium hydroxide solution (0.66 ml) is added to compound 149 (41 mg, 0.01 mmol) followed by stirR1ng for 20 hours at room temperature. The mixture is diluted with water and acidified with a 0.5 N hydrochloR1c acid solution in order to obtain a pH of 6.5. After concentration, the pure product is desalinated on a column of Sephadex G-25, using 9/1 v/v water / actetonitrile. The hexadecasaccharide fractions are combined and freeze-dried to give 26 mg of compound 150 as an amorphous white powder.
TLC: Rf = 0.35, silica gel, 8/7/1.6/4 v/v/v/v ethyl acetate/pyridine/acetic acid/water.

PREPARATION 13 5 6-O-Tert-butyldimethylsilyl-l,2-O-isopropylidene-3-O-
methyl-α-D-glucofuranose (152)
The diol 151 (10 g, 42.7 mmol) is taken up in anhydrous dichloromethane (100 ml) and tert-butyldimethylsilyl chloride (7.1 g, 47.3 mmol) and imidazole (5.8 g, 85.3 mmol) are added. The reaction mixture is stirred at room temperature. After 2 hours, the mixture is diluted in dichloromethane and washed with water. The organic phase is dried over magnesium sulphate and concentrated and the residue is purified by chromatography on a column of silica gel (1/9 v/v ethyl acetate/cyclohexane) in order to obtain the desired product 152 (11.9 g, 80%) in the form of a syrup. [αlD -34o (c 1.9,CHCl3) .
PREPARATION 13 6
6-O-Tert-butyldimethylsilyl-l,2-O-isopropylidene-3-O-methyl-S-C-vinyl-α-D-glucofuranoae (154)
Oxalyl chloride (3.2 ml, 3 6.8 mmol) and dimethyl sulphoxide (5.2 ml, 73.4 mmol) are added, at - 78 °C, to anhydrous dichloromethane (40 ml) and the mixture is stirred for 3 0 minutes. Next, compound 152 (6.4 g, 18.4 mmol) is added and the mixture is stirred for a further 1 hour. triethylamine (15.3 ml, 110.0 mmol) is then added and, after 30 minutes, the reaction mixture is diluted in dichloromethane. Standard processing allows the 5-ulose compound (153) to be obtained, which is used directly for the following reaction. The crude ketone 153 is taken up in anhydrous tetrahydrofuran (100 ml) and IM vinyl-magnesium bromide solution in tetrahydrofuran (28 ml, 27,6 mmol) is added at 0°C. After 1 hour, the reaction mixture is diluted with ammonium chloride and washed with water. The organic phase is dried over magnesium sulphate and concentrated and the residue is purified by chromatography on a column of silica gel (1/9 v/v ethyl acetate/cyclohexane) in order to obtain the

desired compound 154 (70%, 4.8 g) in the form of a syrup.
[α]D -40° (c 1.3, CHCI3) .
Anal. calculated: C, 57.72, H, 9.15. Found: C, 51.11, H, 9.23.
PREPARATION 137
1,2,4,6-Tetra-O-acetyl-3-O-methyl-5-C-vinyl-β-D-
glucopyranose (156)
Compound 154 (3.5 g, 9.4 mmol) is taken up in water (50 ml); IR-120 resin (1 g) is added thereto and the mixture is heated at 80oC for 6 hours. The resin is filtered off and the filtrate is concentrated. The crude product 155 is acetylated using acetic anhydride (12 ml) and pyridine (13 ml) . The excess acetic anhydride is destroyed with methanol and the solvents are concentrated. The residue is extracted with water and dichloromethane. The organic phase is dried over magnesium sulphate, concentrated and, after purification by chromatography on a column of silica (3/2 v/v ethyl acetate/cyclohexane), the tetraacetate compound 156 is obtained in the form of a solid (75%, 2.7 g) . m.p. 50oC. [α]^ -84° (c 1.6, CHCI3) .
Anal, calculated: C, 52.47, H, 6.19. Found: C. 52.51, H, 6.19. Cl-MS: 406 (M + NHJ , 389 (M + 1) .
PREPARATION 138
Methyl 2,3,6-tri-O-benzyl-4-O-(2,4,6-tri-O-acetyl-3-O-methyl-5-C-vinyl-β-D-glucopyraulosyl) -α-D-glucopyranoside (158)
Compound 156 (1.5 g, 4,1 mmol) and compound 157
2.1 g, 4.5 mmol) (P.J. Garegg and H. Hultberg, Carbohydr. Res. 1981, 93, CIO) are dissolved in anhydrous dichloromethane (50 ml) and molecular sieves (4.0 g) are added. The reaction mixture is stirred at room temperature for one hour and TMSOTf (0.95 ml,
5.1 mmol) is then added at -78°C. The reaction mixture

is then left to warm slowly to room temperature. After 2 hours, the reaction mixture is neutralized with triethylamine and filtered through Celite; the filtrate is washed with water. The organic phase is dried over magnesium sulphate and concentrated and the residue is purified by chromatography on silica (4/1 v/v ethyl acetate/cyclohexane) in order to obtain the desired compound 158 (2.77 g, 85%) in the form of a solid, m.p. 47°C.
[α]D -36° (c 0.6, CHCI3) .
Anal, calculated: C, 65.14, H, 6.61. Found: C, 65.09, H, 6.70.
PREPARATION 139
Methyl 2,3,6-O-tri-O-benzyl-4-O-(4,6-O-isopropylidene-3-O-methyl-5-C-vinyl-β-D-glucopyranosyl) -α-D-gluco-pyranoside (160)
Compound 158 (2.7 g, 3.4 mmol) is dissolved in methanol (40 ml) . Sodium (catalytic) is added at 0'=*C and the mixture is stirred at room temperature for 3 hours. The solvent is concentrated and the residue 159 is taken up in anhydrous acetone (40 ml) and 2,2-dimethoxypropane (2 ml) and p-toluenesulphonic acid (catalytic) are added. The reaction mixture is stirred at room temperature overnight. The solvent is evaporated off and the residue is taken up in chloroform and washed with water. The organic phase is dried over magnesium sulphate and concentrated and the residue is purified by chromatography on a column of silica (1/1 v/v ethyl acetate/cyclohexane) in order to obtain the 4', 6'-isopropylidene-O- deR1vative 160 (1.7 g, 70%) in the form of a solid, m.p. 55*^0. [α]^ +13° (c 0.8, CHCI3) .
Anal, calculated: C, 67,97, H, 7.13. Found: C, 67.87, H, 7.15. Cl-MS: 707 (M + 1), 724 (M + NHJ .

PREPARATION 140
Methyl 2,3,6-tri-O-benzYl-4-O-(4,6-O-isopropylidene-3-O-methyl-5-C-vinyl-β-D-mannopyranosyl)-α-D-gluco-pyranoside (162)
Oxalyl chloride (0.35 ml, 4,0 mmol) and anhydrous DMSO (0.57 ml, 8.0 mmol) in anhydrous dichloromethane (10 ml) are stirred at -78°C for 30 minutes. Compound 160 (1.4 g, 2.0 mmol) in anhydrous dichloromethane (10 ml) is added to the solution and the mixture is stirred for a further 45 minutes. The reaction mixture is neutralized by addition of anhydrous triethylamine (1.7 ml, 12,0 mmol) and is then diluted with dichloromethane. After washing with water, the organic phase is dried over magnesium sulphate and concentrated and the residue 161 is used directly for the following reaction without purification. The ketone 161 is taken up in anhydrous tetrahydrofuran (15 ml) and a IN solution of super hydride in tetrahydrofuran (4 ml, 4.0 mmol) is added at -78°C. The reaction mixture is stirred at room temperature for 1 hour and 5% sodium hydroxide (2 ml) and hydrogen peroxide (1 ml) are then added. The solvent is evaporated off and the residue is taken up in ethyl acetate and washed with water. The organic phase is dried over magnesium sulphate and concentrated and the residue is purified by chromatography (2/1 v/v ethyl acetate/cyclohexane) in order to obtain compound 162 (1,0 g, 70%). [α]D -11^ (c 0,5, CHCI3) . Cl-MS: 724 (M + 18), 707 (M + 1).
PREPARATION 141
Methyl 2,3,6-tri-O-benzyl-4-O-(2-O-acGtyl-3-O-methyl-5-
C-vinyl-β-D-mannopyranosyl)-α-D-glucopyranoside (164)
Compound 162 (940 mg, 1.3 mmol) is dissolved in pyridine (3 ml) and acetic anhydride (0.3 ml) is added. The reaction mixture is stirred at room temperature for 3 hours. The excess pyridine and acetic anhydride is evaporated off and the residue 163 is used directly for the deprotection of the isopropylidene using 80% acetic

acid (5 ml) at 60°C for 2 hours. The excess acetic acid is evaporated off and the residue is purified by chromatography on a column of silica gel (4/1 v/v ethyl acetate/cyclohexane) in order to obtain the diol 164 (660 mg, 70%) in the form of a solid, m.p. 53^C. [α]^ -10^ (c 0.8, CHCI3) . Cl-MS: 709 (M + 1), 726 (M + 18).
PREPARATION 142
Methyl 2,3,6-tri-O-benzyl-4-(2-O-acetyl-3-O-methyl-6-O-
tosyl-5-C-vinyl-β-D-mannopyranosyl)-α-D-glucopyranose
(165)
Compound 164 (600 mg, 0.9 mmol) is dissolved in pyridine (3 ml) and tosyl chloride (240 mg, 1.3 mmol) is added. The reaction mixture is stirred at room temperature for 3 hours. The solvent is evaporated off and the residue is diluted with chloroform and washed with water. The organic phase is dried over magnesium sulphate and concentrated and the residue is purified by chromatography on a column of silica gel (l/l v/v ethyl acetate/cyclohexane) in order to obtain the tosyl compound 165 (297 mg, 80%) in the form of a syrup, [α]^ -26*^ (c 0.8, CHCI3) .
PREPARATION 143
Methyl 2,3,6-tri-O-benzyl-4-(2,6-anhydro-3-O-methyl-5-C-vinyl-β-D-lnannopyrallosyl) -α-D-glucopyranoside (166)
Compound 165 (550 mg, 0.6 mmol) is taken up in ethanol (3 ml) and a 0. IN solution of ethanolic sodium hydroxide (5 ml) is then added. The reaction mixture is heated at 70°C for 3 hours and then neutralized with IR-12 0 resin (H* form) and filtered through Celite. After concentration, the residue is purified by chromatography on a column of silica gel (1/1 v/v ethyl acetate/cyclohexane) in order to obtain compound 166
(292 mg, 70%) in the form of a syrup.
[α]^ +13° (c 0.5, CHCI3) . Cl-MS: 666 (M + 18).

PREPARATION 144
Methyl 2,3,6-tri-O-benzyl-4-(benzyl 3-O-methyl-2-O-5-C-methylidene-α-L-idopyranuronate)-α-D-glucopyranoside (167)
Compound 166 (260 mg, 0.4 mmol) is dissolved in dichloromethane (20 ml) , the solution is stirred at -78°C and ozone is then bubbled through for 30 seconds. The colour of the solution becomes pale yellow. Dimethyl sulphide is added to the solution and the reaction mixture is then washed with water. The organic phase is dried over magnesium sulphate and concentrated and is passed directly into the following reaction without further purification. The crude aldehyde is taken up in tert-butanol (16 ml) and 2-methyl-2-butene (5 ml) and water (16 ml) are added. NaH2PO4 (700 mg) and NaClO2 (700 mg) are then added successively to the mixture. The suspension is stirred vigorously at room temperature overnight, diluted with water and extracted with ethyl acetate. The organic phase is dried over magnesium sulphate, concentrated and then passed directly into the following reaction. The crude acid is taken up in dimethyl formamide (25 ml) and tetrabutylammonium iodide (0.7 g, 2.0 mmol), potassium bicarbonate (0.25 g, 2.5 mmol) and benzyl bromide (0.250 ml, 2.1 mmol) are added. The reaction mixture is stirred at room temperature for 5 hours. The reaction mixture is extracted with water and ether. The ether phase is dried over magnesium sulphate and concentrated and the residue is purified by chromatography on a column of silica gel (2/1 v/v ethyl acetate/cyclohexane) in order to obtain the deR1vative 167 (236 mg, 80%) in the form of a syrup. Cl-MS: 774 (M + 18).







Methyl O-(3-O-methyl-2,4,6-tri-O-sulpho-α-D-glucopyrano-syl)-(1-4)-O-(3-O-methyl-2,6-di-O-sulpho-β-D-gluco-pyranosyl)-(1-4)-[O-(3-O-methyl-2,6-di-O-sulpho-α-D-glucopyranosyl)-(1-4)-O-(3-O-methyl-2,6-di-O-sulpho-p -D-glucopyranosyl) -(l-4)]5-O-(2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl)-(l-4)-O-(2,3-di-O-methyl-β-D-glucopyranosyluronic acid)-(1-4)-O-(2,3,6-tri-O-sulpho-α-D-glucopyranosyl)-(1-4)-O-(2,3-di-O-methyl-α-L-idopyranosyluronic acid)-(1-4)-2,3,6-tri-O-sulpho-α-D-glucopyranoside, sodixim salt (168) .
Compound 31 is treated according to Method 5 in order to give 168 (80 % over the three steps). [α]^ + 41 (c = 0.8, water). ESIMS, negative mode: monoisotopic mass = 7133.26; chemical mass = 7138.90; expeR1mental mass = 7137.26 ± 0.0 a.m,u, 1H NMR (D2O) 5 of the main anomeR1c protons: 5.71; 5.48; 5.46; 5.44; 5/17; 5,08; 4.81; 4.78; 4.67 ppm.
An identical procedure allows compounds 169 and 170 to be obtained.



EXAMPLE 4
Methyl O- (2, 3-di-O-methyl-4, 6-di-O-sulpho-α-D-gluco-pyranosyl) -(1-4)-[O-(2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl) - (1-4) ] 15-O- (2, 3-di-O-methyl-β-D-glucopyranosyluronic acid)-(1-4) -O-(2,3,6-tri-O-sulpho-α-D-glucopyranosyl) - (1-4) -O- (2, 3-di-O-methyl-α-L-idopyranosyluronic acid)-(1-4)-2,3,6-tri-O-sulpho-α-D-glucopyranoside, sodium salt (171) .
Compound 51 (55 mg, 10.5 mmol) is treated according to Method 5 in order to obtain, after freeze-drying, the sulpha ted product 187 (50 mg^ 77 % over three steps). [α]^ + 107 (c = 0.52, water). ESIMS, positive mode: monoisotopic mass = 6194.16; chemical mass = 6198.83; expeR1mental mass = 6195.33 ± 1.79, 1H NMR (D2O) 5 of the main anomeR1c protons: 5.71; 5.67; 5.48; 5.43; 5.17; 5.10; 4.68 ppm.
An identical procedure allows compounds 172 and 173 to be obtained.



EXAMPLE 7
Methyl O-(3-O-methyl-2,4,6-tri-O-sulpho-α-D-glucopyran-osyl) - (1-4) -O- (3-O-methyl-2,6-di-O-sulpho-β-D-gluco-pyranosyl)-(1-4)-O-(3-O-methyl-2,6-di-O-sulpho-α-D-glucopyranosyl)-(1-4)-O-(3-O-methyl-2,6-di-O-sulpho-β-D-glucopyranosyl)-(1-4)-[O-(2,3,6-tri-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl) - (1-4) ] ^-O- (2, S-di-O-methyl-S-O-sulpho-α-D-glucopyranosyl) -(1-4)-O-(2,3-di-O-methyl-β-D-glucopyranosyluronic acid)-(1-4)-O-(2,3,6-tri-O-sulpho-α-D-glucopyranosyl) - (1-4)-O-(2,3-di-O-methyl-α-L-idopyranosyluronic acid)-(1-4)-2,3,6-tri-O-sulpho-α-D-glucopyranoside, sodium salt (174).
Compound 75 is treated according to Method 5 in order to give 174 (84 % over the three steps) . [α]^ + 62 (c - 0.46, water). ESIMS, positive mode: monoisotopic mass = 4966.39; chemical mass = 4970.04; expeR1mental mass = 4969.63 ± 0.78 a.m.u. 1H NMR (DjO) 5 of the main anomeR1c protons: 5.69; 5.63; 5.57; 5.46; 5.44; 5,41; 5.15; 5.06; 4.79; 4.66; 4.62; 4.41 ppm.
By working according to Example 7 and using suitable intermediates, Examples 3 to 12 descR1bed in Table III below are prepared.



EXAMPLE 13
Methyl O-(2,3,4,6-tetrα-O-sulpho-α-D-glucopyranosyl)-(1->4)-O-(2,3,6-tri-O-sulpho-α-D-glucopyranosyl)-(l->4) -O-(2,3,6-tri-O-sulpho-β-D-glucopyranosyl)- (l->4) -O-(2,3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl) - (l->4) -O-(2,3, 6-tri-O-methyl-(J-D-glucopyranosyl) - (l->4) - [O-(2, 3, 6-tri-O-methyl-α-D-glucopyranosyl) - (l->4) -O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl) - (l->4)]3-O- (2,3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl) - (1">4) -O-(2, 3-di-O-methyl-β-D-glucopyranosyluronic acid) - (l->4) -O-(6-O-methyl-2,3-di-O-sulpho-α-D-glucopyranosyl)-(l->4)-O-(2,3-di-O-methyl-α-L-idopyranosyluronic acid)-(l->4)-6-O-methyl-2,3-di-O-sulpho-α-D-glucopyranoside (180)
The fully deprotected hexadecasaccharide 150 (26 mg, 0.0084 mmol) is dissolved in dimethylformamide (0.87 ml). Sulphur trioxide/triethylamine complex (125 mg, 0.67 mmol, 80 eq) is added, under a nitrogen atmosphere, and the mixture is stirred for 16 hours at 50*^C. The mixture is cooled to 0°C and aqueous sodium hydrogen carbonate (227 mg, 2.6 mmol) are added. The mixture is concentrated to a small volume and placed on a Sephadex G-25 column, eluted with 9/1 v/v water/acetonitrile. The appropR1ate fractions are separated, concentrated to a small volume, placed on a Dowex XW4 Na+ ion-exchange column in water and the eluate is freeze-dried to give 37 mg of compound 151 as a white powder, [α]20D = +67,6 (c = 1, water) MS ESI: molecular weight is 4370.6 (H+ form) C12BH222O113S16 (Theor. m.w. = 4370.14).
NMR; shift of the anomeR1c protons (ppm): unit 1: 5.17; unit 2 : 5 . 03; unit 3 : 5.41; unit 4 : 4 .42 unit 5: 5.49; unit 6: 4.66; units 7, 9 and 11: 5.67 units 8, 10 and 12: 4.46; unit 13: 5.61; unit 14: 4.94 unit 15: 5.59 ppm; unit 16: 5.69.





The present invention relates to novel synthetic polysaccharides possessing the anticoagulant ^ and antithrombotic pharmacological activities of heparin.
Heparin belongs to the family of glycosaminoglycans (GAGs), which are heterogeneous natural sulphated polysaccharides.
Heparin preparations are mixtures of chains comprising a number of monosaccharide units ranging from 10 to 100 and more. In addition to this size heterogeneity there is a structural heterogeneity, as regards the nature of the constituent monosaccharides and also as regards the substituents which they bear (L. Roden in: The Biochemistry of Glycoproteins and Glycosaminoglycans, Ed by Lennarz W.J,, Plenum Press, New York and London, 267-371, 1980).
Each family of natural GAGs generally possesses a wide range of pharmacological activities. All are combined in the preparations which may be obtained from natural products. Thus, for example, the heparin and heparan sulphates possess an antithrombotic activity which is associated with the simultaneous action of several coagulation factors.
Heparin catalyses, in particular via antithrombin III (AT III), the inhibition of two enzymes involved in the blood coagulation cascade, namely factor Xa and factor IIa (or thrombin) . Low molecular weight heparin (LMWH) preparations contain chains formed of 4 to 3 0 monosaccharides and have the property of acting more selectively on factor Xa than on thrombin.
Certain synthetic oligosaccharides, in particular those described in EP 84,999, have the property of selectively inhibiting, via antithrombin III, factor Xa without having any activity on thrombin.
It is known that the inhibition of factor Xa requires binding of the heparin to AT III via the antithrombin-binding region (ABR), and that the

inhibition of factor Ila (thrombin) requires binding to AT (III) , via ABR, as well as to thrombin via a less well-defined binding region (TBR).
The synthetic oligosaccharides corresponding to the ABR region of heparin are known and manifest an antithrombotic activity in venous thrombosis. These compounds are described in EP 529,715 and EP 621,282 and in Canadian patent 2,040,905.
The efficacy of these oligosaccharides in the prevention of arterial thrombosis is, nevertheless, hampered by their inability to inhibit thrombin.
A synthesis of glycoaminoglycans of heparin type which are capable of inhibiting thrombin via the AT (III) activator presents great difficulties and, indeed, this has never been achieved.
With the aim of rediscovering the activity of thrombin-inhibitor and factor Xa-inhibitor products, in EP-A-0,649,854 it has been proposed to connect two small oligosaccharides (an ABR and a TBR) by a species {'spacer") which is not involved in the biological activity.
It has now been found that novel polysaccharide derivatives may be synthesized relatively simply and are biologically active. They are, in particular, anticoagulant and antithrombotic. Furthermore, on account of the production of these polysaccharides by synthesis, it is possible to selectively modify their structure, and in particular to remove unwanted sulphate substituents involved in the interaction with certain proteins. Thus, polysaccharides may be obtained which are powerful antithrombotic and anticoagulant agents and which may furthermore escape in vivo the action of proteins such as platelet factor 4 (PF4), which neutralize the effect of heparin in particular on thrombin.
Thus, it has been found, surprisingly, that sulphated and alkylated polysaccharides may be powerful antithrombotic and anticoagulant agents depending on

the arrangement of the alkyl and sulphate groups borne by. the carbohydrate skeleton.
More generally, it has been found that by preparing polysaccharide sequences, it is possible to modify with precision the GAG-type activities in order to obtain very active products which have the properties of heparin.
Thus, according to one of its aspects, the present invention relates to a novel synthetic polysaccharide comprising an antithrombin III-binding region consisting of a sequence of five monosaccharides bearing in total two carboxylic acid functions and at least four sulphate groups, this region being extended at its non-reducing end by a thrombin-binding region comprising a sequence of 10 to 25 monosaccharide units chosen from hexoses, pentoses or deoxy sugars in which al 1 the hydroxy1 groups are, independently, etherified with a (C1-C6) alkyl group or esterified in the form of sulphate groups, as well as its salts, in particular its pharmaceutically acceptable salts•
Preferably, the invention relates to a polysaccharide as defined above, characterized in that all its hydroxyl groups are etherified with a methyl or are esterified in the form of a sulpho group and its salts, in particular its pharmaceutically acceptable salts.
The products of the present invention are, in particular, polysaccharides represented by the following formula:

in which
- the wavy line denotes a bond either below or above the plane of the pyranose ring,


denotes a polysacchaR1de Po containing n identical or different monosacchaR1de units, which is linked via its anomeR1c carbon to Pe,

is a diagrammatic representation o£ a monosacchaR1de unit of pyranose structure chosen from hexoses, pentoses and the corresponding deoxy sugars, this unit being linked via its anomeR1c carbon to another monosacchaR1de unit, and the hydroxyl groups of this unit being substituted with identical or different groups -*X, the groups X being chosen from (Gi.Ci)alkyl groups and sulpho groups,
- n is an integer from 10 to 25,
- Pe represents a group,acchaR1de of structure:

in which
- R1 represents a (C1-C6)alkyl or a sulpho group,
- R1a represents R1 or constitutes, with the oxygen atom to which it is attached and the carbon atom beaR1ng the carboxylic :function on the same R1ng, a group
C-CH2-O,
- R represents a (C1-C6)alkyl,
- W represents an oxygen atom or a methylene group,
or one of their salts, in particular a salt which is pharmaceutically acceptable.

It will be noted in general in the present descR1ption that a wavy line denotes a bond either below or above the plane of the pyranose R1ng.
The monosaccharides contained in Po may be identical to or different from each other, and the interglycoside linkages may be of the a or β type.
These monosaccharides are advantageously chosen from the D or L hexoses allose, altrose, glucose, mannose, galose, idose, galactose and talose (in this case h=3) or from the D or L pentoses R1bose, arabinose, xylose and lyxose (in this case h=2) . Other monosaccharides such as, for example, deoxy sugars may also be used (h = 1 and/or -CH2OX = CH3) .
When, in the pentasaccharides Pe, the unit W represents an oxygen atom and R1a is as defined for R1, these pentasaccharides constitute known compounds descR1bed in particular in patents EP 300,099, EP 529,715, EP 621,282 and EP 649,854 as well as in the literature. They are obtained from synthons which are also descR1bed in the literature by C. van Boeckel and M. Petitou, Angew. Chem. Int. Ed• Engl., 1993, 32, 1671-1690.
When, in the pentasaccharides Pe, Rxa is other than R1 and/or W represents a carbon atom, these pentasaccharides are prepared using novel synthons which constitute a further aspect of the invention.
When, in the pentasaccharides Pe, the unit of L-iduronic acid type is replaced with a unit whose conformation is locked by a bR1dge, these pentasaccharides are prepared using novel synthons which constitute a further aspect of the invention.
Thus, according to another of its aspects, the present invention relates to novel intermediates which are useful for the preparation of compounds (I).
The polysaccharide part Po may consist of 10 to 25 al ylated and di- or tR1sulphated monosaccharide units.

The polysaccharide 'part Po may consist of 10 to 2 5 alkylated and mono- or disulphated monosaccharide units.
The polysaccharide part Po may consist of 10 to 25 uncharged and/or partially charged and/or fully charged alkylated monosaccharide units.
The charged or uncharged units may be dispersed along the entire length of the chain or they may, in contrast, be grouped in charged or uncharged saccharide regions.
The linkages may be 1,2; 1,3; 1,4; 1,5; 1,6; and of the a or p type.
In the present descR1ption, it has been chosen to represent the conformations 1C4 for L-iduronic acid and 4C1 for D-glucuronic acid, but it is well known that, in general, the conformation of the monosaccharide units in solution fluctuates. Thus, L-iduronic acid may be of 104 2So or 1C1 conformation.
Preferred compounds according to the invention are those of formula (I.A):

denotes a particular family of polysaccharides Po, linked via their anomeR1c carbon to Pe as defined for (I) ,


is as defined for (I),
- the OXs are as defined for (I) and, for the same
polysaccharide, may be identical or different,
the monosaccharides contained in []m form a disaccharide repeated m times, the monosaccharides contained in []t form a disaccharide repeated t times,
- m ranges from 1 to 8, t ranges from 0 to 5 and p
ranges from 0 to 1, it being understood that
5 and their salts, in particular their pharmaceutically acceptable salts.
Advantageous compounds are the salts whose anion corresponds to formula (I.l):

in which t represents 5, 6 or 7, and the cation is a pharmaceutically acceptable monovalent cation, as well as the corresponding acids.
The salts whose anion corresponds to formula (1.2) :

in which t represents 5, 6 or 7, and the cation is a pharmaceutically acceptable monovalent cation, as well as the corresponding acids, are also advantageous.

The salts whose anion has the formula (1.3):

in which m represents 1, 2 or 3 and t represents 2, 3, 4 or 5, and the cation is a pharmaceutically acceptable monovalent cation, as well as the corresponding acids, are particularly advantageous.
Other preferred compounds according to the invention are those of formula (II.A):

denotes a specific family of polysaccharides Po, linked via their anomeR1c carbon to Pe as defined for (I),

is as defined for (I),

- the groups OX are as defined for (I) and, for the same monosaccharide, may be identical or different,
- the monosaccharide contained in []m' is repeated m' times, the monosaccharide contained in []' is repeated t' times, t' ranges from 0 to 24 and p' ranges from 0 to 24, it being understood that 10 and the pharmaceutically acceptable salts thereof.
The preferred salts of the invention are those chosen from alkali metal cations and even more preferably those in which the cation is Na" or K*.
The following polysaccharides are particularly preferred:
• Methyl O-(3-O-methyl-2,4,6-tR1-O-sulpho-α-D-glucopyranosyl) - (l->4) -O- (3"O-methyl-2, 6-di-O-sulpho-β-D-glucopyranosyl) - (l->4) - [O- (3-0"methyl-2, 6-di-O-sulpho-a-D-glucopyranosyl) - (l-»4) -O- (3-O-methyl-2, 6-di-O-sulpho-β-D-glucopyranosyl) - (l->4) ]4-O- (2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl)-(l->4) -O-(2 , 3-di-O-methyl-(3-D-glucopyranosyluronic acid) - (1—4) -O- (2,3,6-tR1-O-sulpho-α-D-glucopyranosyl)-(l->4) -O-(2,3-di-O-methyl-α-L-idopyranosyluronic acid) - (1-4)-2,3,6-tR1-O-sulpho-α-D-glucopyranoside, sodium salt
• Methyl O-(3-0"methyl-2,4,6-tR1-O-sulpho-α-D-glucopyranosyl) - (l->4) -O- {3-O-methyl-2, 6"di-O-sulpho-β-D-glucopyranosyl) - (1->4) -[O- (3-O-methyl-2; 6-di-O-sulpho-a-D-glucopyranosyl)-(1,4)-O-(3-O-methyl-2,6-di-O-sulpho-3-D-glucopyranosyl) - (l->4) ]s-O- (2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl)-(l->4) -O-(2, 3-di-O-methyl-β-D-glucopyranosyluronic acid)-(1,4)-O-(2,3,6-tR1-O-sulpho-α-D-glucopyranosyl)- (1→4) -O-(2,3-di-O-methyl-α-L-idopyranosyluronic acid)-(1→4) -2,3, 6-tR1-O-sulpho-α-D-glucopyranoside, sodium salt
• Methyl O-(3-O-methyl-2,4,6-tR1-O-sulpho-α-D-glucopyranosyl) - (l->4) -O- (3-O-methyl-2, 6-di-O-sulpho-β-D-glucopyranosyl) - (1→4) - [O- (3-O-methyl-2, 6-di-O-sulpho-α-D-glucopyranosyl) - (1→4) -O- (3-O-methyl-2 , 6-di-O-sulpho-β-D-glucopyranosyl) - (1→4) ] g-O- (2 , 3-di-O-methyl-6-O-sulpho--D-glucopyranosyl) - (1→4) -O- (2, 3-di-O-methyl-β-D-glucopyranosyluronic acid)- (1→4)-O-(2,3,6-

tR1-O-sulpho-α-D-glucopyranbsyl)- (l→4) -O-(2, 3-di-O-methyl-α-L-idopyranosyluronic acid)- (l->4) -2, 3, 6-tR1-O-sulpho-α-D-glucopyranoside, sodium salt
• Methyl O-(2,3-di-O-methyl-4,6-di-O-sulpho-α-D-glucopyranosyl) - (l->4) - [O- (2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl)-(1-^4) -] n-O-(2,3-di-O-methyl-β-D-glucopyranosyluronic acid) -(1, 4) -O-(2, 3, 6-tR1-O-sulpho-α-D-glucopyranosyl)- (1-^4 ) -O-(2, 3-di-O-methyl-α-L-idopyranosyluronic acid) - (l→4) -2,3; 6-tR1-O-sulpho-α-D-glucopyranoside, sodium salt
• Methyl O-(2, 3-di-O-methyl-4,6-di-O-sulpho-α-D-glucopyranosyl) - (1^4) - [O- (2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl)-(l→4) -] 13-O-(2,3-di-O-methyl-β-D-glucopyranosyluronic acid) - (1-^4) -O-(2, 3, 6-tR1-O-sulpho-α-D-glucopyranosyl)- (1^4) -O-(2, 3-di-O-methyl-α-L-idopyranosyluronic acid)- (l→4) -2,3, 6-tR1-O-sulpho-α-D-glucopyranoside, sodium salt
• Methyl O-(2, 3-di-O-methyl-4,6-di-O-sulpho-α-D-glucopyranosyl) - (l->4) - [O- (2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl) - (1→4) -] 15-O- (2, 3-di-O-methyl-3-D-glucopyranosyluronic acid) - (l->4)-O-(2, 3, 6-tR1-O-sulpho-α-D-glucopyranosyl)- (l->4) -O-(2, 3-di-O-methyl-α-L-idopyranosyluronic acid)- (l->4) -2,3, 6-tR1-O-sulpho-α-D-glucopyranoside, sodium salt
• Methyl O-(3-O-methyl-2,4,6-tR1-O-sulpho-α-D-glucopyranosyl) - (1^4) -O- (3-O-methyl-2, 6-di-O-sulpho-(3-D-glucopyranosyl) - (l→4) - [O- (3-O-methyl-2, 6-di-O-sulpho-α-D-glucopyranosyl) - (1-^4) -O- (3-O-methyl-2, 6-di-O-sulpho-β-D-glucopyranosyl) - (1^4) ] 2- [O- (2, 3, 6-tR1-O-methyl-α-D-glucopyranosyl) - (l→4) -O- (2,3, 6-tR1-O-methyl-p-D-glucopyranosyl) - (l->4) ] 2-O-2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl) - (1^4) -O- (2, 3-di-O-methyl-β-D-glucopyranosyluronic acid) - (l→4) -O-(2,3,6-tR1-O-sulpho-α-D-glucopyranosyl) - (1→4) - (2, 3-di-O-methyl-α-L-idopyranosyluronic acid) - (l→4) -2, 3, 6-tR1-O-sulpho-α-D-glucopyranoside, sodium salt
• Methyl O-(3-O-methyl-2, 4, 6-tR1-O-sulpho-α-D-glucopyranosyl) - (l->4) -O- (3-O-methyl-2, e-di-O-sulpho-β-D-glucopyranosyl)- (1-^4) -[O-(3-O-methyl-2, 6-di-O-sulpho-

^ α-D-glucopyranosyl)- (1->4) -O-(3-O-methyl-2,6-di-O-sulpho-β-D-glucopyranosyl)-(1^4) ] — [O-(2,3,6-tR1-O-methyl-α-D-glucopyranosyl)- (1^4) -O-(2, 3, 6-tR1-O-methyl-p-D-glucopyranosyl) - (1->4) ] 3-O-2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl)- (l->4) -O-(2, 3-di-O-methyl-3-D-glucopyranosyluronic acid) - (l->4) -O-(2, 3,6-tR1-O-sulpho-α-D-glucopyranosyl) - (1->4) -(2, 3-di-O-methyl-α-L-idopyranosyluronic acid) - (1-^4) -2,3, 6-tR1-O-sulpho-α-D-glucopyranoside, sodium salt
• Methyl O-(3-O-methyl-2,4,6-tR1-O-sulpho-α-D-glucopyranosyl)- (1^4) -O-(3-O-methyl-2, 6-di-O-sulpho-β-D-glucopyranosyl) - (l->4) -O- (3-O-methyl-2, 6-di-O-sulpho-α-D-glucopyranosyl)- (l->4) -O-(3-O-methyl-2,6-di-O-sulpho-β-D-glucopyranosyl)-(l->4) - [O- (2, 3, 6-tR1-O-methyl-α-D-glucopyranosyl)- (1^4) -O-(2, 3, 6-tR1-O-methyl-p-D-glucopyranosyl) - (1^4) ] 4-O-2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl) - (1^-4) -O- [2, 3-di-O-methyl-β-D-glucopyranosyluronic acid) - (1^4) -O-(2, 3, 6-tR1-O-sulpho-α-D-glucopyranosyl)- (l->4) -[2, 3-di-O-methyl-α-L-idopyranosyluronic acid)- (1->4) -2, 3, 6-tR1-O-sulpho-α-D-glucopyranoside, sodium salt
• Methyl O-(3-O-methyl-2,4,6-tR1-O-sulpho-α-D-glucopyranosyl)- (l->4) -O-(3-O-methyl-2, 6-di-O-sulpho-β-D-glucopyranosyl) - (l->4) -O- (3-O-methyl-2, 6-di-O-sulpho-α-D-glucopyranosyl)- (l->4) -O-(3-O-methyl-2,6-di-O-sulpho-β-D-glucopyranosyl)- (l->4) -[O-(2, 3, 6-tR1-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2, 3, 6-tR1-O-methyl-P-D-glucopyranosyl) - (1^4) ] 3-O-2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl) - (l->4) -O- [2, 3-di-O-methyl-β-D-glucopyranosyluronic acid)- (l->4) -O-{2, 3, 6-tR1-O-sulpho-α-D-glucopyranosyl)- (l->4) -(2, 3-di-O-methyl-α-L-idopyranosyluronic acid) - (l-»4)-2,3, 6-tR1-O-sulpho-α-D-glucopyranoside, sodium salt
• Methyl O-(3-O-methyl-2,4,6-tR1-O-sulpho-α-D-glucopyranosyl) - (l->4) -O- (3-O-methyl-2, 6-di-O-sulpho-β-D-glucopyranosyl)- (l->4) -[O-(2, 3, 6-tR1-O-methyl-α-D-glucopyranosyl) - (l->4)-O-{2, 3,6-tR1-O-methyl-β-D-glucopyranosyl) - (1^4) ]4-O-2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl)- (l->4) -O-(2, 3-di-O-methyl-β-D-

glucopyranosyluronic acid) - (1^4) -O-(2, 3, 6-tR1-O-sulpho-α-D-glucopyranosyl)- (1-^4 ) -(2, 3-di-O-methyl-α-L-idopyranosyluronic acid)-(l->4) -2,3, 6-tR1-O-sulpho-α-D-glucopyranoside/ sodium salt
• Methyl O- (3-O-inethyl-2, 4, 6-tR1-O-sulpho-α-D-glucopyranosyl) - (l->4) -O- (3-O-methyl-2, 6-di-O-sulpho-β-D-glucopyranosyl)- (1-^4) -[O-(2, 3, 6-tR1-O-methyl-α-D-glucopyranosyl)- (l->4) -O-(2, 3, e-tR1-O-methyl-β-D-glucopyranosyl) - (l->4) ] 5-O-2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl)- (l->4) -O-{2, 3-di-O-methyl-β-D-glucopyranosyluronic acid) - (l->4) -O-(2, 3, 6-tR1-O-sulpho-α-D-glucopyranosyl)- (1">4) -(2, 3-di-O-methyl-α-L-idopyranosyluronic acid) - (l-»4) -2, 3, 6-tR1-O-sulpho-α-D-glucopyranoside, sodium salt.
The present invention relates to a process for the preparation of the compounds of formula (I) , wherein, in a first step, a fully protected precursor of the desired polysaccharide (I) , containing a protected precursor of the Pe region (this region being shown in Scheme 1) elongated at its non-reducing end by a protected precursor of the sulphated polysaccharide Po, is synthesized and, in a second step, the negatively-charged groups are then introduced and/or demasked.

In a first approach, the fully protected precursor of the tetrasaccharide part EFGH of the pentasaccharide may be used. A polysaccharide Po which contains at its reducing-terminal end the missing unit

D of Pe is then added in order to obtain, after coupling, the entire ABR which is thus restored.
In another approach, the fully protected precursor of the disaccharide part GH of the pentasaccharide may be used. A polysaccharide Po precursor of the TBR which contains at its reducing-terminal end the missing unit DEF of Pe is then added in order to obtain, after coupling, the entire ABR which is thus restored.
These Pe precursors are synthesized as indicated above from synthons descR1bed in the literature or forming part of the present invention.
The polysaccharide precursor part of Po is synthesized according to reactions which are well known to those skilled in the art, using the methods for synthesizing oligosaccharides (G.J. Boons, Tetrahedron, 1996, 52, 1095-1121) or an oligosaccharide when a glycosidic-linkage-donating oligosaccharide is coupled with a glycosidic-linkage-accepting oligosaccharide in order to lead to another oligosaccharide whose size is equal to the sum of the sizes of the two reactive species.
This sequence is repeated until the desired compound of formula (I) is obtained. The nature and profile of the charge of the desired final compound determine the nature of the chemical species used in the vaR1ous steps of the synthesis, according to rules which are well known to those skilled in the art.
A preferred method for the preparation of the Po precursors according to the present invention is shown in Scheme 2 below:


The term temporary is understood to refer to a substituent which is conserved for a limited number of steps, the term semi-permanent is understood to refer to a substituent which is conserved for a larger number of steps, and the term permanent is understood to refer to a substituent which is conserved to the end of the synthes is; the permanent substituents are removed duR1ng the final step. Certain permanent groups may form part of the final molecule.
In Scheme 2, (a) represents a glycosidic-linkage-donor monosaccharide in which Z is a temporairy protecting group of a hydroxyl function and Y is an anomeR1c-carbon activator, Tn, which may be identical or different, are temporary, semi-permanent or permanent substituents of all the other hydroxyl functions.

The compound (b) which possesses an unsubstituted hydroxy1 group represents a glycosidic-linkage-acceptor monosaccharide in which Tn, which may be identical or different, are temporary, semipermanent or permanent substituents of the hydroxyl groups. T1 is a temporary, semi-permanent or permanent protecting group of the anomeR1c position. It is removed when it is desired to activate .the anomeR1c carbon.
With the aim of obtaining the compounds of the invention, the glycosidic-linkage donor (a) and the glycosidic-linkage acceptor (b) react together to give the disaccharide (c).
The disaccharide (c) obtained above is converted specifically into a glycosidic-linkage-donor disaccharide (d) by removal of T1 and introduction of Y and/or into a glycosidic-linkage acceptor (e) by removal of Z.
Next, the glycosidic-linkage donor (d) and the glycosidic-linkage acceptor (e) react together to give the tetrasaccharide (f) in which t represents 1.
Repetition of this sequence of reactions gives an oligo- or a polysaccharide (f) in which t is greater than 1.
It is also possible, using the process represented in Scheme 2, to obtain a large vaR1ety of fully protected oligo- or polysaccharides such as (g) in which the oligosaccharides [ ] m and [ ] t are fully protected precursors of differently charged regions of the compounds of the invention.
In the following step of the process, the compounds such as (f) and (g) are converted into glycosidic-linkage donors and are coupled to the non-reducing terminal unit of fully protected precursors of Pe.
As has been mentioned above, the oligosaccharide of the non-reducing terminal unit of a glycosidic-linkage-donor polysaccharide (g) may constitute a part of Pe, in the case where (g) is

coupled to the non-reducing terminal unit of a fully protected oligosaccharide which is the precursor of the residue of the structure of Pe.
The compounds of the invention are obtained from their fully protected polysaccharide precursors using the following sequence of reactions:
- the alcohol functions which need to be converted into a sulpho group and the carboxylic acids are deprotected by removal of the Tn groups used to protect them duR1ng the development of the skeleton, then
- the sulpho groups are subsequently introduced.
The compounds of the invention may, naturally, be prepared using vaR1ous strategies known to those skilled in the art of oligosaccharide synthesis.
The process descR1bed above is the preferred process of the invention. However, the compounds of formula (I) may be prepared by other well-known methods of sugar chemistry descR1bed, for example, in Monosaccharides, Their chemistry and their roles in natural products, P.M. Collins and R.J. FerR1er, J. Wiley Sc sons, 1995 and in G.J. Boons, Tetrahedron, 1996, 52, 1095-1121.
The precursor of the part of the pentasaccharide Pe when W represents an oxygen atom and R1a is R1 is prepared according to oligosaccharide synthesis methods and particularly according to the methods descR1bed in patents EP 84,999, EP 3 01,618, EP 454,220 and EP 529,715 and in patent applications EP 93204769 and EP 94202470. When complete protection is carR1ed out, it is possible, using suitable protecting groups, to obtain a free hydroxyl group on position 4 of the non-reducing terminal unit (D) . The fully protected precursor of Pe is then coupled to this position using the known methods of oligosaccharide synthesis.
The pentasaccharide Pe in which W represents a carbon atom and R1a is R1, of formula:


in which T1 and Tn,, which may be identical or different, represent a temporary, semi-permanent or permanent substituent, Z is a protecting group for a hydroxyl function which is itself obtained by a synthesis carR1ed out by means of a radical reaction between a free-radical-generating monosaccharide and a monosaccharide containing a double bond, the C-disaccharide thus obtained then being converted into synthon (II.1) according to the standard methods descR1bed above according to C. van Boeckel and M. Petitou.
The synthon of formula (II. 1) , which is particularly useful in the synthesis of the compounds (II), is of formula:

(II.l) or compound 90 This synthon is prepared according to the reaction scheme descR1bed in Scheme 22 below.

The pentasaccharide Pe which features a substituent R1a which constitutes an L-iduronic acid unit of locked configuration, of formula:

in which R and R1 are as defined for (I) and W represents an oxygen atom, are obtained from the synthon of formula:

in which T1 and Tn, which may be identical or different, represent a temporary, semi-permanent or permanent substituent, Z is a protecting group for a hydroxyl function which is itself obtained by a synthesis carR1ed out according to the methods descR1bed in the literature M.K. Gurjar et al., Tetrahedron letters, 1995, 36, 11, 1937-194 0, 1933-1936 and 1994, 35, 14, 2241-2244.
The synthon of formula (III. 1) which is particularly useful for synthesizing the compounds (III) is of formula:

This synthon is prepared according to the reaction scheme descR1bed in Scheme 34 below.

The intermediates '(II.l) and (III.l) are novel intermediates which are particularly useful for prepaR1ng the compounds (I) according to the invention.
The pentasaccharides Pe may thus be obtained from these disaccharide synthons (II.1) or (III.l) in the way descR1bed in the publication by C.A.A. van Boeckel and M. Petitou, Angew. Chem. Int. Ed, Engl. mentioned above.
The term semi-permanent groups used above is understood to refer to the groups which can be removed firstly after the glycosylation reactions when the carbohydrate skeleton contains the desired number of units, without removing or adversely affecting the other groups present, thereby allowing the introduction of desired functional groups into the positions they occupy.
The permanent groups are groups capable of maintaining the protection of the OH functions duR1ng introduction of the functional groups in place of the semi-permanent groups.
These groups are chosen from those which are compatible with the functional groups introduced after removal of the semi-permanent groups. They are, moreover, groups which are inert towards the reactions carR1ed out to install these functional groups and which may be removed without these functional groups being adversely affected.
According to the invention, the permanent groups are preferably (C1-C6)alkyl groups.
Examples of semi-permanent and/or temporary groups which may be mentioned are benzyl and acetyl, levulinyl, p-methoxybenzyl groups, etc,.
The substituents in position 3 of the uronic units of the target compound may already be present in the starting synthons, along with the substituent R1.
The protecting groups used in the process for prepaR1ng the compounds (I) are those commonly used in sugar chemistry, for example in Protective Groups in

Organic Synthesis, TW Greene, John Wiley & sons, New York, 1981.
The protecting groups are advantageously chosen, for example, from acetyl, halomethyl, benzoyl, levulinyl, benzyl, substituted benzyl, optionally substituted tR1tyl, tetrahydropyranyl, allyl, pentenyl, tert-butyldimethylsilyl (tBDMS) or tR1methylsilylethyl groups (etc.).
The activating groups are those conventionally used in sugar chemistry, for example according to G.J. Boons, Tetrahedron, 1996, 52, 1095-1121, These activating groups are chosen, for example, from imidates, thioglycosides, pentenylglycosides, xanthates, phosphites and halides.
The process descR1bed above makes it possible to obtain the compounds of the invention in the form of salts• In order to obtain the corresponding acids, the compounds of the invention in the form of salts are placed in contact with a cation-exchange resin in acidic form.
The compounds of the invention in acidic form may then be neutralized with a base in order to obtain a desired salt-
For the preparation of the salts of the compounds of formula (I), any organic or inorganic base may be used, giving, with the compounds of formula (I), pharmaceutically acceptable salts.
Sodium hydroxide, potassium hydroxide, calcium hydroxide or magnesium hydroxide is preferably used as ■ base. The sodium and calcium salts of the compounds of formula (I) are the preferred salts.
In step (a) of the process, the protecting groups used are those usually used by those skilled in the art of sugar chemistry, for example according to EP 84,999 or alternatively according to Protective Groups in Organic Synthesis, TW Greene, J, Wiley & sons, 1995.
The compounds (I) thus obtained may optionally be salifled.

The compounds of formula (I) above also compR1se those in which one or more hydrogen or carbon atoms have been replaced with their radioactive isotope, for example tR1tium or carbon-14. Such labelled compounds are useful in pharmacokinetic, metabolism or research studies, and in biochemical tests as ligands.
The compounds according to the invention formed the subject of biochemical and pharmacological studies which showed that they possess very advantageous properties.
The compounds of the present invention which bind selectively to AT III with an affinity equal to or greater than that of hepaR1n possess the anticoagulant and antithrombotic properties of hepaR1n.
The overall antithrombotic activity of the products of formula (I) was evaluated intravenously or subcutaneously in rats, in a model of venous stasis and induction by thromboplastin, according to the method descR1bed by J. Reyers et al. in Thrombosis Research, 1980, 18, 669-674 as well as in a model of arteR1al thrombosis consisting of a shunt implanted between the carotid artery and the jugular vein of rats, as descR1bed by Umetsu et al. Thromb. Haemost., 1978, 39, 74-83. In these two expeR1mental models, the ED50 of the compounds of the invention is at least of the same order as or less than that of the other synthetic hepaR1noids already known (ED50 between 5 and 500 (ig/kg) . The compounds of the invention thus have a
specificity of action and an anticoagulant and antithrombotic activity which are particularly advantageous.
By virtue of their biochemical and pharmaceutical activity, the compounds of the present invention are very advantageous medicines. Their toxicity is entirely compatible with this use. They are also very stable and are thus particularly suitable for constituting the active pR1nciple of pharmaceutical specialty products.

Furthermore, the dompounds of the invention are not neutralized by large doses of cationic platelet proteins such as platelet factor 4 (PF4) released duR1ng activation of these proteins in the process of thrombosis. The compounds of the invention are thus particularly advantageous for the treatment and prevention of thrombosis of arteR1al or venous oR1gin.
They may be used in vaR1ous pathologies which are consecutive to a modification of the haemostasis of the coagulation system, which appears in particular duR1ng disorders of the cardiovascular and cerebrovascular system, for instance thromboembolic disorders associated with atherosclerosis and with diabetes, such as unstable angina, cerebral attacks, restenosis after angioplasty, endarterectomy and the installation of endovascular prostheses; or thromboembolic disorders associated with rethrombosis after thrombolysis, with infarction, with dementia of Lschaemic oR1gin, with peR1pheral arteR1al diseases, with haemodialysis and with auR1cular fibR1llations or alternatively duR1ng the use of vascular prostheses of aortocoronary bR1dges. These products may moreover be used for the treatment or prevention of thromboembolic pathologies of venous oR1gin such as pulmonary embolism. They may be used for preventing or treating thrombotic complications which appear duR1ng surgical interventions or together with other pathologies such as cancer and bacteR1al or viral infections. When they are used duR1ng the installation of prostheses, the compounds of the present invention may coat the prostheses and thus make them haemocompatible. In particular, they may be bound to intravascular prostheses (stents). In this case, they may optionally be chemically modified by introduction of a suitable arm onto the reducing or non-reducing end, as descR1bed in EP 649,854.
The compounds of the present invention may also be used as adjuvants duR1ng endarterectomy performed with small porous balloons.

The compounds of the invention are very stable and are thus particularly suitable for constituting the active pR1nciple of medicines.
According to another of its aspects, the subject of the present invention is thus a pharmaceutical composition containing, as active pR1nciple, a synthetic polysaccharide as defined above.
The invention preferably relates to pharmaceutical compositions containing, as active pR1nciple, a compound of formula (I) , (1.1), (1.2) or (1.3) or one of its pharmaceutically acceptable salts, optionally in combination with one or more inert and suitable excipients.
In each dosage unit, the active pR1nciple is present in amounts adapted to the daily doses envisaged. In general, each dosage unit is conveniently adjusted according to the dosage and type of administration planned, for example tablets, gelatin capsules and the like, sachets, ampules, syrups and the like, drops and transdermal or transmucous patches, such that one dosage unit contains from 0.1 to 100 mg of active pR1nciple, preferably 0,5 to 50 mg.
The compounds according to the invention may also be used in combination with another active pR1nciple which is useful for the desired therapy such as, for example, antithrombotic agents, anticoagulants or platelet-antiaggregating agents, for example such as dipyR1damole, aspiR1n, ticlopidine, clopidogrel or antagonists of the glycoprotein Ilb/IIIa complex.
The pharmaceutical compositions are formulated for administration into mammals, including man, for the treatment of the abovementioned diseases.
The pharmaceutical compositions thus obtained are advantageously in vaR1ous forms such as, for example, injectable or dR1nkable solutions, tablets, coated tablets or gelatin capsules. The injectable solutions are the preferred pharmaceutical forms. The pharmaceutical compositions of the present invention are useful in particular for the preventive or curative

treatment of disorders of/the vascular wall, _ such_ as atherosclerosis, the hypercoagulability states observed, for example, after surgical .operations, tumour development or deregulation of coagulation, which are induced by bacteR1al, viral or enzymatic activators. The dosage may vary widely as a function of the age, weight and state of health of the patient, the nature and seveR1ty of the complaint and the route of administration. This dosage compR1ses the administration of one or more doses of from 0.1 mg to 100 mg per day approximately, preferably from 0.5 to 5 0 mg per day approximately, intramuscularly or subcutaneously, in continuous administrations or administrations at regular intervals.
The subject of the present invention is thus also pharmaceutical compositions which contain, as active pR1nciple, one of the above compounds optionally combined with another active pR1nciple. These compositions are prepared so as to be able to be administered via the digestive or parenteral route.
In the pharmaceutical compositions of the present invention for oral, sublingual, subcutaneous, intramuscular, intravenous, transdermal, transmucous, local or rectal administration, the active ingredient ■nay be administered in unit forms of administration, nixed with standard pharmaceutical vehicles, to animals and to man. The appropR1ate unit forms of administration compR1se oral forms such as tablets, jelatin capsules, powders, granules and oral suspensions or solutions, sublingual and buccal administration forms, subcutaneous, intramuscular. Intravenous, intranasal or intraoccular administration forms and rectal administration forms.
When a solid composition in tablet form is prepared, the main active ingredient is mixed with a Pharmaceutical vehicle such as gelatin, starch, Lactose, magnesium stearate, talc, gum arable or the -ike. The tablets may be coated with sucrose or other suitable mateR1als or alternatively they may be treated

such that they have a sustained or delayed activity and so that they release a predetermined amount of active pR1nciple continuously.
A preparation in gelatin capsules is obtained by mixing the active ingredient with a diluent and pouR1ng the mixture obtained into soft or hard gelatin capsules,
The water -dispersible powders or granules may contain the active ingredient mixed with dispersing agents or wetting agents, or suspending agents, for instance polyvinylpyrrolidone, as well as with sweeteners or flavour enhancers.
For rectal administration, use is made of suppositoR1es which are prepared with binders that melt at rectal temperature, for example cocoa butter or polyethylene glycols.
For parenteral, intranasal or intraoccular administration, steR1le, injectable solutions, isotonic saline solutions or aqueous suspensions which contain pharmacologically compatible dispersing agents and/or wetting agents, for example propylene glycol or butylene glycol, are used.
For transmucous administration, the active
pR1nciple may be formulated in the presence of a
promoter such as a bile salt or in the presence of a
hydrophilic polymer such as, for example,
hydroxypropylcellulose, hydroxypropylmethylcelluose,
hydroxyethylcellulose, ethylcellulose,
carboxymethylcellulose, dextran, polyvinylpyrrolidone, pectins, starches, gelatin, casein, acrylic acids, acrylic esters and their copolymers, vinyl polymers or copolymers, vinyl alcohols, alkoxypolymers, polyethylene oxide polymers and polyethers, or a mixture thereof.
The active pR1nciple may also be formulated in the form of microcapsules, optionally with one or more vehicles or additives.
The active pR1nciple may also be in the form of a complex with a cyclodextR1n, for example α-, β- or

y-cyclodextR1n, 2-hydrcrxypropyl-β-cyclodextR1n or methyl-β-cyclodextR1n.
The active pR1nciple may also be released by a small balloon containing it or by an endovascular expander introduced into blood vessels. The pharmacological efficacy of the active pR1nciple is thus not adversely affected.
Subcutaneous administration is the preferred route.
The following methods, preparations and schemes illustrate the synthesis of the vaR1ous intermediates which are useful for obtaining the polysaccharides according to the invention.
The examples below also illustrate the invention without, however, limiting it.
The following abbreviations are used: TBDMS: tert-butyldimethylsilyl; Lev: levulinyl; Bn: benzyl; Bz: benzoyl; TLC: thin-layer chromatography; 01m: tR1chloroacetimidyl; LSIMS: Liquid Secondary Ion Mass Spectrometry; ESIMS: Electron Spray Ionization Mass Spectrometry; TMS: tR1methylsilyl; TSP: sodium tR1methylsilyltetradeuteR1opropionate; Tf: tR1flate; MS: molecular sieves; All: allyl; PMB: p-methoxybenzyl; SE: tR1methylsilylethyl,
Dowex®, Sephadex®, Chelex® and Toyopearl® are registered trademarks.
In the methods, the preparations and in the examples descR1bed below, general procedures relating to catalytic coupling of the imidates, cleavage of the levulinic esters, catalytic coupling of the thioglycosides, saponification, methylation and selective deprotection of the p-methoxybenzyl group, the deprotection and sulphation of the oligo- and polysaccharides by hydrogenolysis of the benzyl ethers or of the esters, saponification of the esters or sulphations may be performed applying the general methods below to the appropR1ate intermediates.

GENERAL METHODS METHOD 1. Coupling to imidates catalysed by tert-butyldimethylsilyl triflate.
A solution of tert-butyldimethylsilyl triflate in dichloromethane (IM, 0.2 mol/mol of imidate) is added, under argon and at -20°C, to a solution of the imidate and the glycosyl acceptor in dichloromethane (17.5 ml/mmol) in the presence of 4 A molecular sieves. After 1O-20 minutes (TLC), solid sodium hydrogen carbonate is added. The solution is filtered, washed with water, dR1ed and evaporated to dryness. METHOD 2. Cleavage of the levulinic group.
The compound to be deprotected is dissolved in a 2/1 ethanol/toluene mixture (42 ml/mmol) and hydrazine acetate (5 mol/mol) is added. The mixture is left stirR1ng for 15-30 minutes (TLC) and concentrated. METHOD 3. Coupling to the thioglycosides catalysed by N-iodosuccinimide/silver triflate.
The thioglycoside and the glycosyl acceptor are dissolved in anhydrous toluene (18 ml/mmol of thioglycoside) in the presence of 4 A molecular sieves in a round-bottomed flask made of inactinic glass. The mixture is stirred for 1 hour at room temperature. It is cooled to 0°C and N-iodosuccinimide (3 mol/mol of thioglycoside) is added, followed by silver triflate (0.28 mol/mol of thioglycoside). After 1O-15 minutes (TLC), solid sodium hydrogen carbonate is added. After filtration, the solution is washed with aqueous IM sodium thiosulphate solution, water, dR1ed and evaporated.
METHOD 4. Saponification, methylation and selective deprotection of the p-methoxybenzyl group.
Saponification of the esters. The compound to be saponified is dissolved in a 1/1 dichloromethane/ methanol mixture (4 ml/mmol). Sodium methoxide is added and the mixture is stirred for 20 minutes and neutralized with a 50 H+ Dowex® resin. The solution is

concentrated and this compound is used in the following step without puR1fication.
Methylation, Sodium hydR1de is added portionwise, at 0oC, to a mixture of the above crude product and methyl iodide in N,N-dimethylformamide (7 ml/mmol). After complete reaction, the mixture is poured into water and extracted with ethyl acetate. The organic phases are washed with water, dR1ed and evaporated to dryness.
Cleavage of the p-methoxybenzyl. The above crude compound is dissolved in a 9/1 acetonitrile/water mixture (20 ml/mmol) . At O^'C, ammonium ceR1um nitrate (0.5 mol/mol) is added. The reaction mixture is stirred for 2 hours (monitored by TLC), saturated sodium hydrogen carbonate solution is added and the mixture is extracted with ethyl acetate, dR1ed and evaporated. METHOD 5. Deprotection and sulphation of the oligo- and polysaccharides.
Hydrogenolysis of the benzyl ethers and benzyl esters. A solution of the compound in glacial acetic acid is left stirR1ng for 6-12 hours (TLC) under a hydrogen atmosphere (40 bar) in the presence of 5 % Pd/C catalyst (twice the mass of the compound) . After filtration, the product is used directly in the following step.
Saponification of the esters. Aqueous 5 M sodium hydroxide solution (in an amount such that the concentration of sodium hydroxide is 0.5 M at the end of the addition) is added to a solution of an ester in methanol (150 ml/mmol). After 2-5 hours, water is introduced and the mixture is passed through a column of Sephadex® G-25 gel (1.6 x 115 cm) eluted with water. The eluate is concentrated, passed through a Dowex® 50 H"" column (2 ml) and freeze-dR1ed. At this stage, it is confirmed by 1H NMR that all the protecting groups have been removed. If necessary, the product is subjected to a further hydrogenation and/or saponification.
Sulphation. triethylamine/sulphur trioxide complex (5 mol/mol of hydroxy1 function) is added to a

solution of the compound to be sulpha ted in dimethylformamide (5 mg/ml) . After one day at 55oC/ the solution is placed at the top of a Sephadex® G-25 column (1.6 x 115 cm), eluted with 0.2 M sodium chloR1de. The fractions containing the product are concentrated and desalified using the same column eluted with water. The final compound is obtained after freeze-drying.



PREPARATION 1
Ethyl 2,4,6-tri-O-acetyl-3-O-methyl-l-thio-β-D-
glucopyranoside (2).
1,2,4,6-Tetrα-O-acetyl-3-O-methyl-β-D-glucopyranose 1 (69 g, 0.19 mmol), (B. HelfeR1ch et al., J. prakt. Chem., 132, 321 (1932)) is dissolved in toluene (580 ml). Ethanethiol (28 ml, 0.38 mmol) is added, followed by dropwise addition of a solution of trifluoroborane diethyl etherate (1 M in toluene, 190 ml). The mixture is left stirR1ng for 1.5 hours (TLC), solid sodium hydrogen carbonate is introduced and the mixture is filtered, washed with water, dR1ed and concentrated. Chromatography on a column of silica (3/1 cyclohexane/ethyl acetate) gives 2 (37 g, 54 %). [α]D -26 (c = 1. dichloromethane). 1H NMR (CDCl3) . 5 5.05-4.96 (m, 2H, H-2, H-4), 4.39, (d, IH, J = 9.5 Hz, H-1), 4.18-4,12 (m, 2H, H-6, H-6'), 3.60 (m, IH, H-5), 3.50 (dd, IH, J - 9.3 Hz, H-3), 3.41 (s, 3H, OCH3) , 2.65-2.53 (m, 2H, SCH2CH3) , 2.12, 2.11, 2.09 (3s, 9H, 3 Ac), 1.25 (t, IH, SCH2CH3) . PREPARATION 2
Ethyl 4,6-O-benzylidene-3-O-methyl-l-thio-β-D-
glucopyranosidtt (3).
Compound 2 (37 g, 0.1 mmol) is dissolved in a 1/2 mixture of methanol and dichloromethane (1.5 1). 2 M sodium methoxide solution (150 ml) is added. After 0.5 hour at room temperature, the mixture is neutralized with Dowex® 50 (H+) resin, filtered and
concentrated.
The above crude compound is dissolved in anhydrous acetonitrile (1 1) and a,α-dimethoxytoluene (30 ml, 0.2 mol) and camphorsulphonic acid (2.3 g, 10 mmol) are added. The mixture is left stirR1ng for 1.5 hours (TLC), triethylamine (1.4 ml) is added and the mixture is concentrated. The residue obtained is precipitated in ethyl ether and gives 3 (27 g, 81 %) . [α]D -60 (c = 1.63, dichloromethane). 1H NMR (CDCl3)

7.51-7.34 (m, 5H, Ph) , 5.55 (s, IH, CeHsCH) , 4.5 6 (d, IH, J = 9.2Hz, H-1), 2.75 (m, 2H, SCHsCifs) . 1.32 (t, 3H, SCH2CH3) .
Anal. Calculated for C16H22O5S (326.41) : C, 58.58; H, 6.79; S, 9.82. Found: C, 58.99; H, 6.74; S, 9.75. PREPARATION 3
Ethyl 2-O-bon2yl-4,S-O-benzylidone-S-O-methyl-l-thio-β-D-glucopyranoside (4).
Sodium hydR1de (2.00 q, 83.3 mmol) is added, at
0oC, to a solution of 3 (23 g, 71.0 mmol) and benzyl
bromide (11 ml, 93.0 mmol) in N,N-dimethylformamide
(200 ml) . The mixture is left stirR1ng for 2 hours
(TLC), methanol is added and the reaction mixture is
poured into water. It is extracted with ethyl acetate,
washed with water, dR1ed and concentrated. The residue
is precipitated in ethyl ether in order to obtain 4
(18.8 g, 63 %). m.p. 123°C. [α]D -35 (c - 0.63,
dichloromethane) . 1H NMR (CDCl3) 5 7.5O-7.25 (m, lOH,
2Ph), 5.55 (s, IH, CeHsCif) , 4.54 (d, IH, J = 9.7 Hz, H-
1), 4.34 (m, IH, H-6), 3.75 (t, IH, J = 10,2 Hz, H-6'),
3.65 (s, 3H, OCH3) , 3.6O-3.33, (m, 4H, H-5, H-4, H-3, H-
2), 2.75 (m, 2H, SCH2CH3) . 1.32 (t, 3H, SCHaCifa) .
Anal. Calculated for C23H28O5S (416.54): C, 66.32, H, 6.78; S, 7.70. Found: C, 66.25; H, 7.28; S, 7.54. PREPARATION 4
Ethyl 2,6-di-O-benzyl-3-O-methyl-l-thio-β-D-
glucopyranosida (5).
A solution of trifluoroacetic anhydR1de (0.65 ml, 4.50 mmol) in trifluoroacetic acid (16 ml, 0.21 mmol) is added, under argon, to a solution of 4 (28.8 g, 69.0 mmol) and triethylsilane (33 ml, 0.21 mmol) in dichloromethane (120 ml). The mixture is left stirR1ng for 2 hours and diluted with ethyl acetate and aqueous 1 M sodium hydroxide solution is added to pH 9. The mixture is extracted with ethyl acetate, washed with water, dR1ed and evaporated to dryness. The residue is puR1fied on a column of silica

f-
(3/1 and then 2/1 cyclohexane/ethyl acetate) in order o" obtain 5 (17.4 q, 60 %). [α]D -47 (c = 1, dichloromethane) . 1H NMR (CDCl3) 5 7.45-7.25 (m, lOH, 2Ph), 4.47 (d, IH, J = 9,3 Hz, H-1), 3.66 (s, 3H, OCH3) , 3.61-3.40 (m, 2H, H-4 and H-5) , 3.36-3.19 (m, 2H, H-2 and H-3), 2.73 (m, 2H, SCH2CH3) , 1.31 (t, 3H, SCH2CH2) .
Anal. Calculated for C23H30O5S (418,55) : C, 66.00, H, 7,22; S7.66. Found C, 65.62; H, 7,28; S, 7.21.
PREPARATION 5
Ethyl 2,6-O-di-benzyl-4-O-lovulinyl-3-O-methyl-l-thio-p-D-glucopyranoaide (6).
Compound 5 (17.3 g, 41.4 mmol) is dissolved in
anhydrous dioxane (400 ml). Levulinic acid (9.60 g,
83.0 mmol), 1-(3-dimethylaminopropyl)-3-
ethylcarbodiimide (16 g, 86 mmol) and 4-dimethylaminopyR1dine (1 g/ 8.3 mmol) are added. The mixture is left stirR1ng for 4 hours, extracted with ethyl acetate, washed successively with aqueous 5 % potassium hydrogen sulphate solution, with water, with saturated aqueous sodium hydrogen carbonate solution, with water, dR1ed and concentrated. The residue is puR1fied on a column of silica (6/1 toluene/ethyl acetate) in order to obtain pure 6 (19.9 g, 93 %). [α]d - 5 (c - 1.46, dichloromethane) . LSIMS, positive mode: m/z thioglycerol + NaCl, 539 (M+Na)+; thioglycerol + KF, 555 (M+K)^. 1H NMR (CDCl3) 5 7.4O-7.20 (m, lOH, 2Ph) , 4.92 (m, IH, H-4), 2.8-2.4 (m, 6H, SCH2CH3 and 0(C:0)CH2CH2(C:0)CH3) , 2.16 (s, 3H, 0(C:0)CH2CH2(C:0)CH3) , 1,32 (t, IH, J = 7.3 Hz, SCH2CH3) .
Anal. Calculated for CaaHssOiS (516.55): C, 65.09, H, 7.02; S, 6.21. Found: C, 65,30; H, 7.03; S, 5.75.
PREPARATION 6 Allyl 4,6-O-benzylidene-3-O-methyl-β-D-glucopyranoside
(7).
trifluoromethanesulphonic acid (1.10 ml, 0.012 mol) is added to a suspension of commercial 3-O-methylglucose (135 g, 0.7 mol) in allyl alcohol (1 1) ,

The mixture is heated at 120oC for 2 hours. It is neutralized by addition of triethylamine (2 ml) and evaporated to dryness.
α,α-Dimethoxytoluene (136 ml, 0.9 mol) and camphorsulphonic acid (25 g, 0.13 minol) are added to the above crude compound dissolved in N,N-dimethylformamide (2 1) . The mixture is heated at 80°C for 1 hour under vacuum. It is neutralized by addition of triethylamine (21 ml) and extracted with ethyl acetate, washed with water, dR1ed and concentrated in order to obtain a solid α/p mixture = 3/2, (144 g, 57 %), This mixture is recrystallized from ethanol in order to obtain pure 7-a (60 g, 26 %) . Chromatography
of part of the mother liquors on a column of silica (3/1 cyclohexane/ethyl acetate) gives pure 7-p (7.6 g), 7-a/p (6.8 g) and pure 7-a (1.4 g).
Compound 7-P: [α]D "43 (c = 1, dichloromethane). m.p.: 131°C. 1H NMR (CDCl3) 5 7.5O-7.2 6 (m, 5H, Ph) , 6.01-5.90 (m, IH, OCH2(CH:CH2) ) , 5.55 (s, IH, CeHsCff) , 5.38-5.32 (m, 2H, OCH2(CH:CH2) ) , 4.47 (d, IH, J -7.5 Hz, H-1) , 4.42-4.32 (m, 2H, H-6' and 0Ci?2 (CH :CH2) ) , 4.21^4.15 (m, IH, OCH2 (CHrCHa) ) , 3.80 (dd, IH, J = 10.2 Hz, H-6), 3.67 (s, 3H, OCH3) .
Anal. Calculated for C17H22O6 (322.36) : C, 63.34; H, 6.88. Found: C, 63.23; H, 7.12.
PREPARATION 7
Allyl 2-O-acetyl-4,6-O-benzylidane-3-O-ni«thyl-β-D-gluco-
pyranosida (8).
7 (11.5 g, 35.7 mmol) is dissolved in dichloromethane (100 ml) and acetic anhydR1de (4.0 ml, 42.8 mmol), triethylamine (6.40 ml, 46.4 mmol) and 4-dimethylaminopyR1dine (440 mg, 3.60 mmol) are added. The mixture is left stirR1ng for 2 hours (TLC), washed successively with aqueous 5 % potassium hydrogen sulphate solution, with water, with saturated aqueous sodium hydrogen carbonate solution, with water, dR1ed and evaporated until a solid 8 (12.3 g, 95%) is obtained, m.p. 115°C. [α]D -68 (c = 1, dichloro-

methane). LSIMS, positiv4 mode: m/z thioglycerol + NaCl, 387 (M+Na)+; thioglycerol + KF, 403 (M+K)+. 1H NMR
(CDCl3) 5 7.51-7.34 (m, 5H, Ph), 5.98-5.78 (m, IH, OCH2(CH:CH2) ) , 5.56 (s, IH, C6H5C6H5CH) , 5.32-5.17 (m, 2H, OCH2(CH:Cif2) ) , 4.99 (dd, J = 8 Hz, IH, H-2), 4.55
(d, J = 7.9 Hz, IH, H-1), 4.39-4.29 (m, 2H, H-6 and OC;f2{CH:CH2) ) , 4.14-4.04 (m, IH, OH2 (CH: CH2) ) 3.82 (t, J = 10.2Hz, IH, H-6'), 3.60 (s, 3H, OCH3) , 2.12 (s, 3H, Ac) .
Anal. Calculated for C19H24O7 (366.39): C, 62.63; H, 6.64. Found: C, 62.63/ H, 6.64.
PREPABATZON 8
Allyl 2-O-acetyl-6-O-benzyl-3-O-mathyl-β-D-glucopyrano-
side (9).
A solution of trifluoroacetic anhydR1de (306 fil, 2.10 mmol) in trifluoroacetic acid (10 ml) is added, at 0oC, to a solution of 8 (12.0 g, 33.3 mmol) and triethylsilane (21.3 ml, 133 mmol) in anhydrous dichloromethane (50 ml) . The mixture is left stirR1ng for 4 hours (TLC), diluted with ethyl acetate and aqueous IM sodium hydroxide solution is added to pH 9. The mixture is extracted with ethyl acetate, washed with water, dR1ed and concentrated. The residue is puR1fied on a column of silica (8/5 cyclohexane/acetone) to give pure 9 (10 g, 82 %) . [α]D -40 (c = 1.06, dichloromethane). 1H NMR (CDCl3) 6 7.35-7.28 (m, 5H, Ph) , 5.87-5.79 (m, IH, OCH2 (CH :CH2) ) , 5.28-5.14 (m, 2H, OCH2(CH:CH2) ) , 4.43 (d, IH, J = 7.9Hz, H-1), 4.41-4.28 (m, IH, OCH2 (CH:CH2) ) , 4.1O-4.02 (m, IH, OCff2(CH:CH2) , 3.77-3.75 (m, 2H, H-6 and H-6'), 3.51 (s, 3H, OCH3), 3.30 (dd, IH, J = 8.9Hz, H-3), 2.8 (d, IH, OH) ,
Anal. Calculated for C19H26O7 (366.39): C, 62.28/ H, 7.15. Found: C, 61.73: H. 7.19.



PREPARATION 9
Allyl 2-O-acetyl-6-O-benzyl-3-O-methyl-4-O-(2,6-di-O-benzyl-4-O-levulinyl-3-O-mothyl-α-D-glucopyranosyl)-β-D-glucopyranoside (10).
The thioglycoside 6 (17.4 q, 33.7 mmol) and the glycosyl acceptor 9 (10.3 q, 28.1 mmol) are dissolved in dichloroethane (150 ml) . 4 A molecular sieves are added and the mixture is left stirR1ng for 1 hour. A solution of N-iodosuccinimide (8.30 g, 33.7 mmol) and trifluoromethanesulphonic acid (0.30 ml, 3.30 mmol) in a mixture of dichloroethane and ethyl ether (415 ml, 1:1) is added, at -20oC and under an argon atmosphere. The mixture is left stirR1ng for 10 minutes (TLC) , sodium hydrogen carbonate is added and the mixture is filtered, washed successively with aqueous IM sodium thiosulphate solution, with water, with saturated aqueous sodium hydrogen carbonate solution, with water, dR1ed and concentrated. The residue is puR1fied on a column of silica (11/1 dichloromethane/ethyl acetate) in order to give the pure disaccharide 1O-a (11.7 g, 52 %) . [α]D + 38 (c = 1.01, dichloromethane) . 1H NMR (CDCl3) 5 7.35-7.23 (m, 15H, 3 Ph) , 5,9O-5.80 (m, IH, OCH2(CH:CH2) ) , 5.47 (d, IH, J = 3.6 Hz, H-1'), 5.27-5.14 (m, 2H, OCH2(CH:CH2) ) , 5.05-4.90 (m, 2H, H-4' and H-2), 4.42 (d, IH, J = 7.6 Hz, H-1), 4,38-4,32 (m, IH, OCH2(CH:CH2) ) , 4.15-4.0 (m, IH, OCH2(CH:CH2) ) , 3.90 (dd, IH, J = 8.8 Hz, H-4), 3.54, 3.34 (2 s, 6H, 2 OCH3) . 2.75-2.40 (m, 4H, 0 (C:0) CH2CH2 (C:0) CH3) , 2.16, 2.10 (2 s, 6H, Ac and 0 (C:0) CH2CH2 (C:0) CH3) .
Anal. Calculated for C45H56O14 (820.94) : C, 65.84; H, 6.88. Found: C, 65.74; H, 6.90. PREPARATION 10
Prop-1'-onyl-2-O-acetyl-6-O-benzyl-3-O-methyl-4-O-(2,6-di-O-benzyl-4-O-levulinyl-3-O-methyl-α-D-glucopyranoayl)-β-D-glucopyranoaida (11).
1,5-Cyclooctadienebis[methyldiphenylphos-phine] iR1dium hexafluorophosphate (5.80 mg, 0.70 μmol) is added to a solution of 10 (1.36 g, 1.66 mmol) in peroxide-free tetrahydrofuran (4.30 ml). The solution

is degassed, placed under an argon atmosphere and hydrogen is introduced. The mixture is left stirR1ng for 10 minutes (TLC) and evaporated. The residue is taken up in dichloromethane, washed with saturated aqueous sodium hydrogen carbonate solution, with water, dR1ed and concentrated. The residue is puR1fied on a column of silica (3/1 toluene/ethyl acetate) in order to obtain pure 11 (1.04 g, 76 %), [α]D + 47 (c = 1.1, dichloromethane). LSIMS, positive mode: m/z thioglycerol + NaCl, 951 (M + Na)+; thioglycerol + KF, 967 (M + K)+ 1H NMR (CDCl3) δ 7.34-7.23 (m, 15H, 3 Ph) , 6.21-6.16 (m, IH, 0 (CH:CH) CH3) , 5.45 (d, IH, J = 3.5 Hz, H-1'), 5.13-4.97 (m, 3H, H-4', H-2 and 0 (CH: Cif) CH3) , 4.6 (d, IH, J = 7.55 Hz, H-1), 3.96 (dd, IH, J = 8.9 Hz, H-4'). 3.54, 3.34 (2 s, 6H, 2 OCH3) , 2.74-2.36 (m, 4H, 0(C:0)CH2CH2(C:0)CH3) , 2.15, 2.08 (2s, 6H, Ac and 0{C:0)CH2CH2{C:0)CH3) 1.56-1.51 (dd, 3H, 0 (CH : CH) CH3)
Anal. Calculated for C45H56O14 (820.94) : C, 65.84; H, 6.88. Found: C, 66.21; H, 6.92. PREPAHATIOM 11
2-O-Acetyl-6-O-benzyl-3-O-methyl-4-O-(2,6-di-O-benzyl-4-O-levulinyl-3-O-methyl-α-D"-glucopyranosyl) -a,p-D-glucopyranose (12).
A solution of mercuR1c chloR1de (3.9 g, 14.3 mmol) in a mixture of acetone and water (26 ml, 5/1) is added dropwise to a solution of 11 (7.8 g, 9.53 mmol) and mercuR1c oxide in the same solvent (80 ml) . The mixture is left stirR1ng for 1 hour, filtered and concentrated. It is extracted with dichloromethane and the extracts are washed with saturated aqueous potassium iodide solution, with water, dR1ed and concentrated. The residue is puR1fied on a column of silica (10/1 and then 4/1 dichloromethane/acetone) in order to obtain 12 (6.70 g,
90 %) .
[α]D + 92 (c = 1.37, dichloromethane) . TLC, RF 0.31, 14/1 dichloromethane/acetone. 1H NMR (CDCl3) δ 7.37-7.24 (m, 15H, 3 Ph), 5.46 (d, IH, J = 3.5 Hz, H-1'), 5.37 (d, J = 3.6 Hz, H-la), 4.58 (d, J = 8 Hz, H-lp), 3.54,

3.39, 3.36 (3s, 6H, 2 OCH3) , 2.75-2.4 (m, 4H, 0(C,:0)CH2CH2(C:O)CH3) , 2.16, 2.15 (2s,6H,Ac and 0 (C:O)CH2CH2(C:O)CH3) , 2,16, 2.15 (2s, 6H, Ac and 0(C:O)CH2CH2(C:O)CH3) .
Anal. Calculated for C42H52O14 (780.83); C, 64.60; H, 6.71. Found: C, 65.09; H, 6.82. PREPARATION 12
2-O-Acetyl-6-O-benzyl-3-O-methyl-4-O-(2,6-di-O-bonzyl-4-O-levulinyl-3-O-methyl-α-D-glucopyranosyl)-a,p-D-glucopyranose trichloroacetimidate (13).
Compound 12 (5.00 g, 6.4 mmol) is dissolved in
dichloromethane (50 ml) and trichloroacetonitrile
(3.9 ml, 38.8 mmol) and potassium carbonate (1.5 g,
11.6 mmol) are added, under argon. The mixture is left
stirR1ng for 16 hours (TLC) and filtered. The filtrate
is puR1fied on a column of silica (8/1 and then 4/1
dichloromethane/acetone) in order to give a mixture
(a/p = 60/40) of imidates 13 (5.22 g, 87 %). TLC, RF
0.66 and 0.51, 20/1 dichloromethane/acetone. -1H NMR
(CDCl3) δ 8.62-8.59 (2s, IH, N:H-a and p), 7.37-7.23 (m,
15H, 3 Ph) , 6.51 (d, J = 3.7 Hz, H-la) , 5.81 (d, J =
7.1 Hz, H-IP) , 5.50 (d, IH, J = 3.5 Hz, H-1') , 3.55,
3.41, 3.37 (3s, 9H, 3 OCH3) , 2.75-2.40 (m, 4H,
0(C:O)CH2CH2(C:O)CH3) , 2.16, 2.07, 2.04 (3s, 6H, Ac and
(C:O)CH2CH2(C:O)CH3) .
Anal. Calculated for C44H52CI3NO14 (925.26): C, 57.12; H, 5.66; N, 1.51. Found: C, 57.31; H, 5.87; N, 1.55.
PREPARATION 13
Allyl 2-O-acetyl-6-O-benzyl-3-O-methyl-4-O-(2,6-di-O-bon2yl-3-O-methyl-α-D-glucopyranosyl)-β-D-glucopyranoside (14).
Compound 10 (3.11 g, 3.80 mmol) is treated according to Method 2 in order to give 14 (2.70 g, 97 %) . [α]D + 25 (c = 1.7, dichloromethane). LSIMS, positive mode: m/z thioglycerol + NaCl, 745 (M+Na)+; thioglycerol + KF, 761 (M+K)+. 1H NMR (CDCl3) d 7.33-7.20 (m, 15H, 3 Ph) , 5.87-5.78 (m, IH, OCH2 (CH:CH2) ) , 5.50 (d, IH, J = 3.5 Hz. H-1'), 5.3O-5.17 (m, 2H,

OCH(CH:Cff2) ) , 5.02 (dd, (H, H-2), 4.43 (d, IH, J = 7.6 Hz, H-1), 4.34-4.28 (m, IH, 0CH2 (CH: CH2) ) , 4.12-4.02 (m, IK, OCH2(CH:CH2) ) , 3.63, 3.36 (2s, 6H, 2 OCH3) , 2.10 (3, 3H, Ac).
Anal. Calculated for C40H50O12 (722.84); C,
6 6.4 7; H, 6.97. Found: C, 66.31; H, 7.24,



PREPAIIATION 14
Allyl O-(2,6-di-O-benzyl-4-O-levulinyl-3-O-methyl-α-D-glucopyranosyl) - (1^4) -O- (2-O-acetyl-6-O-benzyl-3-O-methyl-β-D-glucopyranosyl) - (1-^4) -O- (2, 6-di-0"benzyl-3-O-methyl-α-D-glucopyranosyl) - (1→4) -2-O-acotyl-6-O-benzyl-3-O-niothyl-β-D-glucopyranosido (15) .
A mixture of the imidate 13 (4.22 g, 4.56 mmol) and the glycosyl acceptor 14 (2.63 g, 3.64 mmol) is treated according to Method 1. The product is puR1fied on a column of silica (3/2 and then 1/1 toluene/ethyl ether) in order to give the tetrasaccharide 15 (4.31 g, 80 %) . [αlo + 52 (c = 0.66, dichloromethane) . 1H NMR (CDCl3) 6 7.35-7.23 (m, 30H, 6 Ph) , 5.83-5.79 (m, IH, OCH2(Cff:CH2) ) , 5.47 (d, 2H, J = 3.5 Hz, H-1'" and H-1'), 5.25-5.14 (m, 2H, OCH2 (CH :CH2) ) , 4.38 (d, IH, J = 7.7 Hz, H-1"), 4.30 (d, IH, J = 8 Hz, H-1), 4.32-4.25 (m, IH, OCH2(CH:CH2) ) , 4.08-4.02 (m, IH 0Cif2 (CH rCHa) ) , 3.56, 3.53, 3.34, 3.27 (4s, 12H, 4 OCH3) , 2.78-2.4 0 (m, 4H, 0(C:O)Cff2CH2(C:O)CH3) , 2.15, 2.09, 1.85 (3s, 9H, 2 Ac and 0 (C :0) CH2CH2 (C :0) CH3) .
Anal. Calculated for C82H100O25 (1485.7): C, 66.29; H, 6.78. Found: C, 66.10; H, 6.79. PREPARATION 15
O- (2,6-Di-'O-b«nzyl-4-O-levulinyl-3-O-xBothyl-α-D-glucopyranosyl) - (l->4) -O- (2-O-acotyl-6-O-b«nzyl-3-O-methyl-β-D-glucopyranosyl)- (l->4) -O-(2,S-di-O-baznyl-S-O-mothyl-α-D-glucopyranoayl) - (1^4) -2-O-acatyl-6-O-benzyl-3-O-methyl-a,p-D-glucopyranosa (16).
Compound 15 (2.30 g, 1.54 mmol) is treated as in Preparation 10. After 10 minutes, a solution of N-bromosuccinimide (0.30 g, 1.70 mmol) in dichloromethane (15 ml) and water (5.50 ml) is added to the reaction mixture. The mixture is left stirR1ng for 5 minutes (TLC) . It is diluted with dichloromethane, washed with saturated aqueous sodium hydrogen sulphate solution, with water, dR1ed and concentrated. The residue is puR1fied on a column of silica (3/2 toluene/ethyl acetate) in order to give pure 16 (1.57 g, 71% over the two steps) . [α]o +69 (c = 0.87, dichloromethane) .

11H NMR {CDCl3) S 7,38-7.20{m, 30H, 6 Ph) , 5.47 (d, IH, J = 3.5 Hz, H-1"' and H-1'), 5.36 (d, IH, J = 3.5 Hz, H-la) , 4.55 (d, IH, J = 8 Hz, H-1), 4.36 {d, IH, J = 8 Hz, H-1"), 3.56, 3.54, 3.39, 3.36, 3.28 (5s, 9H, 3 OCH3), 2.75-2.35 (m, 4H, 0 (C :0) CH2CH2 (C : 0) CH3) , 2.16, 2.13, 2.12, 1.86 (4s, 9H, 2 Ac and 0(C:O)CH2CH2(C:O)CH3) . PREPARATION 16
O- (2,6-Di-O-benzyl-4-O-levulinyl-3-O-iaothyl-α-D-glucopyranosyl) - (l->4) -O- (2-'O-acetyl-6-O-bonzyl-3-O-methyl-β-D-glucopyranosyl) - (l->4) -O- (2 , 6-di-O-b«nzyl-3-O-mothyl-α-D-glucopyranosyl) - (l->4) -2-O-acatyl-6-O-benzyl-3-O-methyl-a,P-D-glucopyranoa# trichloroacetimidata (17).
A mixture of 16 (1.5 g, 1.04 mmol), trichloroacetonitrile (0.63 ml, 6.22 mmol) and potassium carbonate (0.26 g, 1,87 mmol) in dichloromethane (15 ml) is left stirR1ng for 16 hours at room temperature. The solution is filtered and
concentrated. It is puR1fied on a column of silica (4/1
toluene/acetone + 1 7 of triethylamine) in order to
/ 00
give 17 (1.47 g, 89.6 %), TLC, R? 0.5 7/2 toluene/acetone. PREPARATION 17
Allyl O-(2,6-di-O-benzyl-3-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2-O-acatyl-6-O-benzyl-3-O-mathyl-β-D-glucopyranoayl) - (l->4) -O- (2, 6-di-O-b«nzyl-3-O-methyl-α-D-glucopyranosyl) - (1-^4) -2-O-acotyl-6-O-benzyl-3-O-mathyl-β-D-glucopyranosida (18).
The delevulination of 15 (1.3 g, 0.87 mmol) is carR1ed out according to Method 2 in order to give 18 (1.05 g, 86 %). [α]D +40 (c = 0.6, dichloromethane). 1H NMR (CDCl3) 6 7.36-7.23 (m, 30H, 6 Ph) , 5.83-5.78 (m, IH, OCH2(CH:CH2) ) , 5.50 (d, IH, J = 3.5 Hz, H-1''), 5.47 (d, IH, J = 3.5 Hz, H-1'), 5.25-5.21 (dd, IH, J = 1.6 Hz, J = 17 Hz, OCH2(CH:CH2) ) , 5.15-5.13 (dd, IH, J =
1.4 Hz, J = 10 Hz, OCH2(CH:CH2) ) , 4.38 (d, IH, J =
6.4 Hz, H-1"), 4.31 (d, IH, J = 6.5 Hz, H-1), 4.08-4.02

(m, IH, OCH2(CH:CH2) ) , 3.5§ (m, IH, H-4'"), 3.67, 3.53, 3.39, 3.29 (4s, 12H, 4 OCH3) , 2.09, 1.86 (2s, 6H, 2 Ac). PREPARATION 18
Allyl O- (2 , 6-di-O-benzyl-4-O-levulinyl-3-O-inethyl-α-D-glucopyranosyl) - (1—^4) - [O- (2-O-acetyl-6-O-benzyl-3-O-methyl-β-D-glucopyranosyl)- (1→4) -O-(2,6-di-O-benzyl-3-O-methyl-α-D-glucopyranosyl) - (l->4) ] 3-2-O-acetyl-6-O-benzyl-3-O-methyl-β-D-glucopyranoside (19).
A mixture of 18 (842 mg, 0.53 mmol) and 17 (1.17 g, 0.74 mmol) is treated according to Method 1. The product is puR1fied on a Toyopearl® HW-50 column (110 X 3.2 cm; 1/1 dichloromethane/ethanol) in order to give 19 (1.44 g, 85%). [α]D + 57 (c = 1.01, dichloromethane) . 1H NMR (CDCl3) d 7.35-7.20 (m, 60H, 12 Ph) , 5.83-5.78 (m, IH, OCH2 (Cif: CH2) ) , 5.24-5.21 (dd, IH, OCH2(CH:CH2) ) , 5.16-5.13 (dd, IH, OCH2 (CH rCHz) ) , 3.59, 3.56, 3.51, 3.47, 3.33, 3.26 (6s, 24H, 8 OCH3) , 2.75-2.35 (m, 4H, 0 (C :0) CH2Ci/2 (C :0) CH3) , 2.15, 2.09, 1.85, 1.84 (4s, 15H, 4 Ac and 0 (C :0) CH2CH2 (C :0) Cif3) ;
6 of the main anomeR1c protons: 5.48; 4.37;
4.29; 4.23 ppm.
Anal. Calculated for CO56047H188 (2815.51): C, 66.56; H, 6.73. Found: C, 66.22; H, 6.75.



PREPARATION 19
O-(2 , 6-Di-O-benzyl-4-O-levulinyl-3-O-methyl-α-D-glucopyranosyl)-(1-4)-[O-(2-O-acetyl-6-O-benzyl-3-O-methyl-β-D-glucopyranosyl)-(1-4)-O-(2,6-di-O-benzyl-3-O-methyl-α-D-glucopyranosyl) - (1-4) ]3-2-O-acetyl-6-O-benzyl-3-O-methyl-a,p-D-glucopyranose (20).
Compound 19 (720 mg, 0.25 mmol) is treated as in Preparation 15. The product is puR1fied on a column of silica (3/2 and then 4/3 toluene/ethyl acetate) in order to obtain 20 (555 mg, 78 %). [α]D +70 (c = 0.94, dichloromethane). TLC, RF 0.43, 1/1 toluene/ethyl acetate. PREPARATION 20
O- (2,6-Di-O-benzyl-4-O-lavTilinyl-3-O-methyl-α-D-glucopyranosyl)-(1-4)-[O-(2-O-acetyl-6-O-benzyl-3-O-methyl-β-D-glucopyranoayl)-(1-4)-O-(2,6-di-O-banzyl-3-O-methyl-α-D-glucopyranoayl) - (1-4) ] 3-2-O-acatyl-6-O-benzyl-3-O-mothyl-a,p-D-glucopyrano3a trichloroacetiaidate (21).
Compound 20 (540 mg, 0.195 mmol) is treated as in Preparation 16. The product is puR1fied on a column of silica (3/2 toluene/ethyl acetate + 1 % of
triethylamine) in order to give a mixture (a/p = 27/73) of the imidates 21 (455 mg, 80 %) . TLC, RF 0.48, 3/2 toluene/ethyl acetate. 1H NMR (CDCl3) δ 8.60, 8.59 (2s, IH, N:Ha and p) , 7.35-7.21 (m, 60H, 12 Ph) , 2.75-2.40 (m, 4H, 0(C:O)CH2CH2(C:O)CH3) , 2.16, 2.06, 2,04, 1.85, 1.84 (5s, 15H, 4 Ac and 0 (C:O) CH2CH2 (C:O) CH3) .
1H NMR (CDCl3) δ of the main anomeR1c protons: 6.50; 5.79; 5.51; 5.48; 4.29; 4.25 ppm.



PREPARATION 21
Phenyl 2,4,6-tri-O-acetyl-3-O-mothyl-l-thio-α-D-glucopyranosida (22).
1,2,4,6-Tetrα-O-acetyl-3-O-methyl-β-D-glucopyranose 1 (5.23 g, 14.4 mmol) is dissolved in toluene (45 ml). Thiophenol (3.0 ml, 28.8 mmol) is added, foil owed by dropwise addition of trifluoroborane diethyl etherate (1.77 ml, 14.4 mmol) and the mixture is then heated at 50°C for 0.5 hour. It is diluted with dichloromethane, washed with saturated aqueous sodium hydrogen carbonate solution, with water, dR1ed and concentrated. The residue is puR1fied on a column of silica (5/2 cyclohexane/ethyl acetate) to give 22-a (1.00 g, 17 %) and 22-p (2.71 g, 46 %) .
22-a, RF 0.44, 3/2 cyclohexane/ethyl acetate.
[α]D + 230 (c = 1, dichloromethane) . ESIMS, positive
mode: m/z + NaCl, 435 (M+Na)%- +KF, 451 (M+K)\ 1H NMR
(CDCl3) 5 7.46-7.27 (m, 5H, Ph) , 5.89 (d, IH, J =
5.6 Hz, H-1), 5.05-4.97 (m, 2H, H-2 and H-4), 4.49-4.42
(m, IH, H-5), 4.25-4.18 (m, IH, H-6), 4.05-4.00 (m, IH,
H-6'). 3.66, (dd, IH, J = 9.5 Hz, H-3) , 3.51 (s, 3H,
OCH3), 2.16, 2.12, 2.00 (3s, 9H, 3 Ac).
Anal. Calculated for C19H24O8S (412.46) : C, 55.33; H, 5.87; S, 7.77. Found: C, 55.25; H, 5.90; S, 7.75.
PREPARATION 22
Phenyl 4,6*O*benzylidenO-2,3-di-O-methyl-l-thio-α-D-glycopyranoside (23) .
Compound 22 (970 mg, 2.35 mmol) is dissolved in a 2/1 mixture of methanol and dichloromethane (18 ml) . 2M sodium methoxide solution (150 ml) is added. After 0,5 hour at room temperature, the mixture is neutralized with Dowex® 50 (H+) resin, filtered and concentrated.
a,α-Dimethoxytoluene (0.7 ml, 4.0 mmol) and camphorsulphonic acid (51 mg, 0.22 mmol) are added to the above crude reaction mixture in acetonitrile (22 ml) . The mixture is left stirR1ng for 1 hour.

neutralized by addition of triethylamine (0.50 ml) and concentrated.
Sodium hydR1de (73.0 mg, 2.80 mmol) is added, at 0°C, to a solution of the above crude product and methyl iodide (163 μ1, 4.0 mmol) in N,N-dimethylformamide (9 ml). The mixture is left stirR1ng for 1 hour and methanol is added. The mixture is extracted with ethyl acetate, washed with water, dR1ed and concentrated to obtain 23 in solid form (840 mg, 94 %). m.p.: 178°C. [α]D + 330 (c = 1, dichloromethane). ESIMS, positive mode: m/z + NaCl, 411.4 (M+Na)+, +KF, 427.4 (M+K)+, 1H NMR (CDCl3) S 7.5O-7.24 (m, lOH, 2 Ph) , 5.71 (d, IH, J = 3.4 Hz, H-1) , 5.52 (s, IH, C6H5CH) , 3.62 (s, 3H, OCH3) , 3.55 (s, 3H, OCH3) .
Anal. Calculated for C21H24O5S (388.48): C, 64.92; H, 6,23; S, 8.25. Found: C, 64.87; H, 6.17; S, 7.85.
PREPARATION 23
Phenyl 6-O-ban2yl-2,3-di-O-inothyl-l-thio-α-D-
glucopyranoside (24).
Compound 23 (792 mg, 0.47 mmol) is treated as in Preparation 4. The product is puR1fied on a column of silica (7/2 and then 2/1 cyclohexane/ethyl acetate) to give 24 (318 mg, 80 %). [α]D + 243 (c = 1, dichloromethane). ESIMS, positive mode: m/z + NaCl, 413 (M+Na)\- +KF, 429 (M+K)*. 1H NMR (CDCl3) δ 7.52-7.22 (m, lOH, 2 Ph), 5.71 (d, IH, J = 5.3 Hz, H-1), 3.64 and 3.49 (2s, 6H, 2 OCH3) , 3.36 (dd, IH, H-3) •
Anal. Calculated for C21H26O5S (390.50) : C, 64.59; H, 6.71; S, 8.21. Found: C, 64.05; H, 6.88; S, 7.74.
PREPARATION 24
Phenyl O- (2 , 6-di-O-benzyl-4-O-le'VTilinyl-3-O-methyl-α-D-glucopyranosyl) - (1-4) -O- (2-O-acetyl-6-O-banzyl-3-O-methyl-β-D-glucopyranosyl)-(1-4)-6-O-benzyl-2,3-di-O-methyl-l-thio-α-D-glucopyranoside (25).
A mixture of 13 (436 mg, 0.47 mmol) and 24 (153 mg, 0.39 mmol) is treated according to Method 1.

The product is puR1fied column (Sephadex® LH20, 1/1 ethanol/dichloromethane) to give pure 25 (30 9 mg, 68 %). [α]D -^ 144 (c = 1, dichloromethane) . ESIMS, positive mode: m/z + NaCl, 1175 (M+Na)%- +KF, 1191 {M+K)\ 1H NMR (CDCl3) δ 7.51-7.21 (m, 25H, 5 Ph) , 5.73 (d, IH, J = 5.2 Hz, H-1), 5.48 (d, IH, J = 3.5 Hz, H-1"), 4.46 (d, IH, J = 8 Hz, H-1'), 3.7, 3.54, 3.5, 3.31 (4s, 12H, 4 OCH3), 2.7O-2.41 (m, 4,H, 0(C:O)CH2CH2(C:O)CH3) , 2.16, 2,01 (2s, 6H, 1 Ac and
0(C:O)CH2CH2(C:O)Cff3) •
Anal. Calculated for C63H76O18S: C, 65.61; H,
6.64; S, 2.78. Found: C, 65.02; H, 6.60; S, 2.72. PREPARATION 25
Methyl O-(2,6-di-O-benzyl-4-O-levulinyl-3-O-mathyl-α-D-glucopyranosyl)-(1-4)-O-(2-O-ac«tyl-6-O-benzyl-3-O-mothyl-β-D-glucopyranosyl)-(1-4)-O-(6-O-b«nzyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(benzyl 2,3-di-O-methyl-β-D-glucopyranosyluronate)-(1-4)-O-(3,6-di-O-acetyl-2-O-bonzyl-α-D-glucopyranoayl)-(1-4)-O-(benzyl 2,3-di-O-methyl-α-L-idopyranosyluronate)-(1-4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (27).
A solution of N-iodosuccinimide (92 mg, 0.38 mmol) and triflic acid (37.5 |il, 0.38 mmol) in a 1/1 solution of 1,2-dichloroethane and ethyl ether (22 ml) is added, at -25°C and under argon, to a mixture of 25 (451 mg, 0.39 mmol) and 26 (434 mg, 0.31 mmol) , (P. Westerduin, et al. BioOrg. Med. Chem., 1994, 2, 1267) in 1,2-dichloroethane (7.5 ml) in the presence of 4 A molecular sieves (400 mg) . After 30 minutes, solid sodium hydrogen carbonate is added. The solution is filtered, washed with sodium thiosulphate solution, with water, dR1ed and evaporated. The residue is puR1fied on a column of Sephadex® LH-20 (1/1 dichloromethane/ethanol) and then on a column of silica (1/1 and then 2/3 cyclohexane/ethyl acetate) to give pure 27 (487 mg, 64 %) . [α]D + 63 (c = 0.54, dichloromethane), TLC, Rf 0.28, 2/1 cyclohexane/ethyl acetate. ESIMS, positive mode: m/z + NaCl, 2454 (M+Na)""; +KF, 2 4 69 (M+K)\ 1H NMR (CDCl3) 5 7.38-7.2 (m, 5 OH,

10 Ph), 3.56, 3.52, 3.48, 3.46, 3.44, 3.42, 3.39, 3.30, 3.17 (95, 27H, 9 OCH3) , 2.75-2.4 (m, 4H, 0(C:O)Cf/2CH2C:O)CH3) , 2.15, 1.98, 1.97, 1.87, (4s, 12H, 3 Ac and 0 (C :0) CH2CH2 (C :0) Cffs) ; main anomeR1c protons: 5.57; 5.47; 5.30; 5.18; 4.57; 4.29; 4.08. PREPARATION 26
Methyl O-(2,6-di-O-benzyl-3-O-methyl-α-D-glucopyranosyl)-(1-4)-(2-O-acetyl-6-O-bonzyl-3-O-methyl-β-D-glucopyranosyl)-(1-4)-O-(6-O-bsnzyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(benzyl 2,3-di-O-methyl-β-D-glucopyranosyluronate)-(1-4)-O-(3,6-di-O-acetyl-2-O-benzyl-α-D-glucopyranosyl)-(1-4)-O-(benzyl 2,3-di-O-methyl-α-L-idopyranosyluronate)-(1-4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (28).
The delevulinization of 27 (498 mg, 0.2 mmol) is carR1ed out according to Method 2 to give 28 (402 mg, 84 %). [α]o + 64 (c = 1, CH2CI2) . ESIMS, positive mode: m/z 2352.9 (M+NH4)*. 1H NMR (CDCl3) S 7.38-7.20 (m, 50H, 10 Ph) , 3.67, 3.52, 3.49, 3.46, 3.44, 3.41, 3.40, 3.28, 3.17 (9s, 27H, 9 Ac) , 2.65 (d, IH, J = 2.14 Hz, OH), 1.98, 1.96, 1.87 (3s, 9H, 3 Ac) ; main anomeR1c protons: 5.55; 5.49; 5.30; 5.18; 4.56; 4.31; 4.08.
Anal. Calculated for C127H152O41 (2334.48) : C, 65.34; H, 6.56. Found: C, 65.40; H, 6.62. PREPARATION 27
Methyl O-(2,6-di-O-banzyl-4-O-levulinyl-3-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(2-O-acetyl-6-O-b«nzyl-3-O-mothyl-β-D-glucopyranoayl)-(1-4)-[O-(2,6-di-O-benzyl-3-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(2-O-ac«tyl-6-O-bonzyl-3-O-methyl-β-D-glycopyranosyl) - (1-4) ]4-O- (6-O-benzyl-2,3-di-O-niethyl-α-D-glucopyranosyl) - (1-4) -O-(benzyl 2,3-di-O-methyl-β-D-glucopyranosyluronate)- (1-4)-O-(3,6-di-O-acetyl-2-O-benzyl-α-D-glucopyranosyl)-(1-4) -O- (benzyl 2,3-di-O-methyl-α-L-idopyranosyl\aronate) -(1-4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (29).
A mixture of 21 (340 mg, 1.16 mmol) and 28
(256 mg, 1.09 mmol) is treated according to Method 1.
The residue is puR1fied on a column of Toyopearl® HW-40

(3.2 X 70 cm, 1/1 dichloromethane/ethanol) to give the pure 15-mer 29 (421 mg, 76 %). [α]D +65 (c = 1, dichloromethane) . ESIMS, positive mode: m/z + KF, 2584.3 (M+2K)2+- 1736.5 (M+3K)3+1H NMR (CDCl3) δ 7.35-7.18 (m, 105H, 21 Ph), 2.75-2.4 (m, 4H, 0(C:O)C/f2CH2(C:O)CH3) , 2.15, 1.97, 1.95, 1.87, 1.84, 1.83 (6s, 24H, 7 Ac, and 0 (C : 0) CH2CH2 (C : 0) CH3) ; main anomeR1c protons: 5.55; 5.4 8; 5.30; 5.18; 4.56; 4.29; 4.22; 4.08.



PREPARATION 28
Methyl O-(2,6-di-O-benzyl-3-O-methyl-α-D-gluco-pyranosyl)-(1-4)-O-(2-O-acetyl-6-O-benzyl-3-O-methyl-β-D-glucopyranosyl)-(1-4)-[O-(2,6-di-O-benzyl-3-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(2-O-acetyl-6-O-benzyl-3-O-methyl-β-D-glycopyranosyl)- (1-4)]4-O-(6-O-benzyl-2,3-di-O-methyl-α-D-glucopyranoayl)-(1-4)-O-(benzyl 2,3-di-O-methyl-β-D-glucopyranosyluronate)-(1-4)-O-(3,6-di-O-acetyl-2-O-benzyl-α-D-glucopyranosyl)-(1-4)-O-(benzyl 2,3-di-O-methyl-α-L-idopyranosyluronate)-(1-4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (30).
Compound 29 (342 mg, 0.067 mmol) is treated according to Method 2 to give 30 (253 mg, 75 %). [α]D + 5 9 (c = 0.92, dichloromethane) . ESIMS, positive mode: m/z + KF, 2535.6 (M+2K)^\ 1H NMR (CDCl3) 6 of the main anomeR1c protons: 5.55; 5.50; 5.48; 5,30; 4.56; 4.30; 4.22; 4.08.
Anal. Calculated for C275H328O85 (4993.37): C, 65.57; H, 6.60. Found: C, 65.09; H, 6.57, PREPARATION 29
Methyl O-(2,6-di-O-benzyl-4-O-levulinyl-3-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(2-O-acetyl-6-O-benzyl-3-O-methyl-β-D-glucopyransoyl)-(1-4)-[O-(2,6-di-O-benzyl-3-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(2-O-acetyl-6-O-benzyl-3-O-methyl-β-D-glycopyranosyl)- (1-4)]e-O-(6-O-benzyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(benzyl 2,3-di-O-methyl-β-D-glucopyranoayluronate)- (1-4)-O-(3,6-di-O-acetyl-2-O-benzyl-α-D-glucopyranoayl)-(1-4)-(benzyl 2,3-di-O-methyl-α-L-idopyranosyluronate)-(1-4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (31).
A mixture of 17 (32.7 mg, 20.6 mmol) and 30 (80.7 mg, 16.3 mmol) is treated according to Method 1. The product is puR1fied on a column of Toyopearl® HW-40 (1/1 dichloromethane/ethanol) to give 19-mer 31 (60 mg, 59 %) . [α]D + 61 (c = 0,82, dichloromethane) . ESIMS, positive mode: m/z + NaCl, 2162.4 (M+3Na)3+- +KF, 2178.5 (M+3K)2+.
1H NMR (CDCl3) δ of the main anomeR1c protons:
5.55; 5.48; 5.30; 5.17; 4.56; 4.22; 4.08.



PREPARATION 30
Ethyl O-(4,6-O-benzylidene-α-D-glucopyranosyl)-(1-4)-6-
O-trityl-l-thio-β-D-glucopyranoside (33).
To a suspension of 32 (50.0 g, 0.105 mol)
(J. Westman and M. Nilsson, J. Carbohydr. Chem., 1995,
14(7), 949-960) in dichloromethane (620 ml) under argon
are added triethylamine (35 ml, 0.252 mol), trityl
chloR1de (29.3 g, 0.105 mol) and
4-dimethylaminopyR1dine (1.28 g, 10 mmol). The mixture is maintained at reflux for 2 hours (TLC), left to cool to room temperature, diluted with dichloromethane (500 ml) and then washed successively' with cold aqueous 10 % potassium hydrogen sulphate solution, with water and with saturated sodium chloR1de solution. The solution is dR1ed, concentrated and filtered on a column of silica (65/35 and then 50/50 toluene/acetone) in order to obtain the crude product 33, which is
sufficiently pure to be used in the following step. An analytic sample is chromatographed. [α]D +53 (c =
0.74, dichloromethane) . ESIMS, negative mode: m/z 715 (M-H)+. 1H NMR (CD2CI2) 5 7.52-7.25 (m, 20H, 4Ph) , 5.42 (s, CeHsCff) , 4.97 (d, J = 3.5 Hz, H-1') , 4.40 (d, J = 9.6 Hz, H-1), 3.82 (t, J = 9.3 Hz, H-3') , 3.70, 3.68 (m, 2H, H-3, H-4), 3.60 (dd, J « 2.0, 11.0 Hz, H-6a) , 3.55 (td, J = 5.2, 9.7, 9.7 Hz, H-5') , 3.49-3.45 (m, 3H, H-2, H-2', H-5), 3.38 (dd, J = 10.5 Hz, H-6'a), 3.33 (dd, H-6'b), 3.3O-3.27 (m, 2H, H-4', H-6b), 2.9O-2.77 (m, 2 H, SCH2CH3) , 1.4O-1.37 (t, 3H, CH2CH3) .
Anal. Calculated for C40H44O10S: C, 67.02; H, 6.19; S, 4.47. Found: C, 66.83; H, 6.19; S, 4.19. PREPARATION 31
Ethyl O- (4, 6*-O->banzylidene-2,3-di-O-mathyl-α-D-gluco-pyranosyl)-(1-4)-2,3-di-O-mothyl-6-O-trityl-l"thio-β-D-glucopyranoside (34) .
Methyl iodide (34 ml, 0.536 mol) is added dropwise, under argon, to a solution of compound 33 (64.1 g) in N,N-dimethylformamide (600 ml). The solution is cooled to 0°C and sodium hydR1de (13.5 g, 3.536 mol) is added slowly. The suspension is stirred


for 2 hours at room temperature and then cooled to 0°C
and methanol (35 ml) is added dropwise and, after stirR1ng for 2 hours, the mixture is diluted in ethyl acetate (500 ml) and water (600 ml). The aqueous phase is extracted with ethyl acetate and the organic phases are washed with water, dR1ed and concentrated. The residue 34 is sufficiently pure for the following step. An analytical sample is puR1fied on a column of silica (70/30 cyclohexane/acetone). [α]D + 45 (c = 0.83, dichloromethane). ESIMS, positive mode: m/z + NaCl, 795 (M+Na)%- +KF, 811 (M+K)+, 1H NMR (CDCl3) δ 7.52-7.19 (m, 20H, 4Ph), 5.51 (d, J = 3-3 Hz, H-1') / 5.43 (s, CeHsC/f) , 4.45 (d, J = 9.8 Hz, H-1), 3.60, 3.59, 3.51, 3.49 (4s, 12H, 4OCH3), 2.86 (q, 2H, J = 7.5 Hz, SCH2CH3) , 1.40 (t, 3H, SCH2CH3) .
Anal • Calculated for C44H52O10S: C, 68.37; H, 6.78; S, 4.15. Found: C, 68.28; H, 6.98; S, 4.09. PREPARATION 32
Ethyl O-(2,3-di-O-methyl-α-D-glucopyranosyl)-(1-4)-2,3-di-O-methyl-l-thio-β-D-glucopyranosida (35).
A suspension of crude product 34 (67.4 g) is heated at 80oC for 2 hours in aqueous 60 % acetic acid solution (470 ml)• The reaction mixture is cooled, filtered and concentrated. The residue is treated with sodium methoxide (940 mg) in methanol (200 ml) for 1 hour. The solution is then neutralized with Dowex® 50WX4 (H*) resin and then filtered, concentrated and puR1fied on a column of silica (60/40 toluene/acetone) in order to obtain 35 (27.9 g, 60 % over three steps). [α]D + 26 (c = 1.07, dichloromethane). ESIMS, positive mode: m/z, +NaCl, 465 (M+Na)+• +KF, 481 (M+K)+, 1H NMR (CDCl3) δ 5.62 (d, J = 3.9 Hz, H-1'). 4.35 (d, J = 9.8 Hz, H-1), 3.64, 3.64, 3.59, 3.58 (4s, 12H, 4OCH3) , 1.29 (t, 3H, J = 7.4 Hz, SCH2CH3) .
Anal. Calculated for C18H34O10S. H2O: C, 46.94; H, 7.87; S, 6.96. Found: C, 47.19; H, 7.72; S, 6.70.

PREPARATION 33
Ethyl O-(6-O-acetyl-2,3-di-O-methyl-α-D-gluco-pyranosyl)-(1-4)-6-O-acotyl-2,3-di-O-methyl-l-thio-β-D-glucopyranoside (36) .
A solution of triol 35 (5.86 g, 13.2 mmol) and N-acetylimidazole (3.21 g, 29.1 mmol) in 1,2-dichloroethane (120 ml) is refluxed for 16 hours. A further portion of N-acetylimidazole (440 mg, 3.96 mmol) is added and the mixture is stirred for 4 hours. It is left to cool to room temperature and methanol (2 ml) is then added. The mixture is stirred for a further 1 hour and then diluted with dichloromethane (1 1), washed successively with cold aqueous IM hydrochloR1c acid solution, with cold water, with saturated aqueous sodium hydrogen carbonate solution, with water, dR1ed and concentrated. The residue is chromatographed (3.5/1 toluene/acetone) in order to obtain the diacetate 36 (3.97 g, 57 %). [α]D + 33 (c = 1.90, dichloromethane) . ESIMS, positive mode: m/2, +NaCl, 549 (M+Na)%- +KF, 565 (M+K)+, 1H NMR (CDCl3) S 5.51 (d, J = 3.9 Hz, H-1'), 4.34 (d, J = 9.8 Hz, H-1), 3.64, 3.63, 3.59, 3.56 (4s, 12H, 4OCH3) , 2.11, 2.06 (2s, 6H, 2Ac), 1.31 (t, 3H, J = 7.4 Hz, SCH2CH3) .
Anal- Calculated for C22H38O12: C, 50.17; H, 7.27; S, 6.09. Found: C, 50.15; H, 7.49; S, 5.89. PREPARATION 34
Ethyl O-(6-O-acetyl-4-O-levulinyl-2,3-di-O-mothyl-α-D-glucopyranosyl)-(1-4)-6-O-ac«tyl-2,3-di-O-mathyl-l-thio-β-D-^glucopyranosida (37) .
To a solution of diacetate 36 (19.4 g, 36.8 mmol) in dioxane (400 ml), under argon, are added levulinic acid (7.53 ml, 73.5 mmol), l-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloR1de (14.1 g, 73.5 mmol) and 4-dimethylaminopyR1dine (900 mg, 7.35 mmol). The mixture is stirred for 3.5 hours, diluted with dichloromethane (1.5 1) and then washed successively with water, with aqueous 10 % potassium hydrogen sulphate solution, with water, with aqueous 2 % sodium hydrogen carbonate solution, with

water and then dR1ed and concentrated. The residue is chromatographed (97/3 and then 79/21 dichloromethane/ acetone) in order to obtain the deR1vative 37 (21.8 g,
95 %) . [α]D + 40 (c = 0.72, dichloromethane) . ESIMS, positive mode: m/z, + NaCl, 647 (M+Na)+; +KF, 663
(M+K)+, 1H NMR (CDCl3) δ 5.56 (d, J = 3.9 Hz, H-1'), 4.35 (d, J = 9.8 Hz, H-1), 3.64, 3.60, 3.58, 3.55 (4s, 12H, 4OCH3) , 2.7 6-2.71 (m, 4H, 0 (C:O) CH2CH2 {C:O) CH3) , 2.19, 2.08, 2.07 (3s, 9H, 2Ac and 0 (C : 0) CH2CH2 (C :0) Cffa) , 1.31 (t, 3H, J = 7.4 Hz, SCHsCffs) .
Anal. Calculated for C27H44O14S: C, 51.91; H, 7.10; S, 5.13. Found: C, 51.88; H, 7.05; S, 4.96. SCHEME 10: Synthesis of dlsaccharides 38 and 40

PREPARATION 35
O-(6-O-Ac#tyl-4-O-levulinyl-2,3-di-O-inethyl-α-D-glucopyranosyl) -(1-4) -6-O-acetyl-2,3-di-O-niothyl-a,p-D-glucopyranosa trichloroacetimxdata (38).
To a solution of thioglycoside 37 (9.53 g, 15.3 mmol) in a 1/1 dichloromethane/ethyl ether mixture (180 ml) are added water (1.4 ml, 76.3 mmol), N-iodosuccinimide (6.84 g, 30.5 mmol) and silver triflate (0.51 g, 1.98 mmol). After 15 minutes (TLC) , saturated aqueous sodium hydrogen carbonate solution (5 ml) is added and the reaction mixture is diluted in dichloromethane (1.5 1), washed with water, aqueous IM sodium thiosulphate solution and aqueous 2 % sodium hydrogen carbonate solution. The solution is dR1ed and concentrated and the residue is puR1fied on a column of silica (80/40 and then 100/0 ethyl acetate/cyclohexane)

in order to give a solid which is used, without
characteR1zation, in the following step. A solution of
the above compound (7.88 q, 13.6 mmol) in
dichloromethane (120 ml) under argon is treated with caesium carbonate (7.08 g, 21.7 mmol) and trichloroacetonitrile (6.81 ml, 67.9 mmol). After 40 minutes (TLC), the mixture is filtered, concentrated and puR1fied (8 5/15 toluene/acetone) in order to obtain the imidate 38 (9.16 q, 83 % over two steps). [α]D + 118 (c = 1.00, dichloromethane) . ESIMS, positive mode: m/z +NaCl, 745 (M+Na)+,- 741 (M+NH4)^ 1H NMR (CDCl3) δ 8.66, 8.65 (2s, IH, a and P N:H), 6.52 (d, J = 3.6 Hz, H-la), 5.70 (d, J = 7.5 Hz, H-IP), 5.58 (d, J = 3.7 Hz, H-1' ) , 2.7 8-2.57 (m, 4H, 0 (C :0) CH2CH2 (C : 0) CH3) , 2.18, 2.07, 2.06 (3s, 9H, 2Ac and 0 (C :0) CH2CH2 (C : 0) Cffs) .
Anal. Calculated for C27H40CI3NO15- 0.5 H2O: C, 4 4.18; H, 5.63; N, 1.98. Found: C, 44.14; H, 5.61; N, 1.97.
PREPARATION 36
2- (trimethylsilyl)ethyl O- (6-O-acatyl-4-O-lavulinyl-2,3-di-O-m0thyl-α-D^glucopyranosyl)-(1-4)-6-O-acatyl-2,3-di-O-mothyl-a,p-D-glucopyranosida (39).
The thioglycoside 37 (10.6 g, 16.94 minol) is treated according to Method 3 with 2-(trimethylsilyl)ethanol (4.8 ml, 33.90 mmol) in a 1/2 dichloromethane/ethyl ether mixture (105 ml) . The residue obtained is puR1fied by chromatography (1/1 acetone/dichloromethane) in order to obtain compound 39 (9.80 g, 85 %) in the form of a mixture of anomers (a/p 65/35). ESIMS, positive mode: m/z +NaCl, 703 (M+Na)+, 1H NMR (CDCl3) δ 5.58 (d, J = 3.9 Hz, H-1') / 4.94 (d, J = 3.5 Hz, H-la), 4.26 (d, J = 7.7 Hz, H-lp) , 2.76-2.56 (m, 4H, 0(C:O)CH2CH2(C:O)CH3) , 2.17, 2.08, 2.05 (3s, 9H, 2Ac and 0 (C:O) CH2CH2 (C:O) CH3) , 1.18-0.88 (m, 2H, OCH2Cff2Si (CH3)3) , 0.02 (s, 9H, CH2CH2Si (CH3)3) .
Anal. Calculated for C3oH520i5Si: C, 52.92; H, 7.69. Found: C, 53.29; H, 7.75.



according to Method 3 in a 1/2 dichloromethane/ethyl ether mixture (105 ml). The residue is purified by chromatography on silica (3/1 and then 9/1 acetone/cyclohexane) in order to obtain 41 (4.81 g, 69 %) . [alo + 143 (c = 0.56, dichloromethane) . ESIMS, positive mode: m/z, + NaCl, 1167 (M+Na) %• + KF, 1183 (M+K) +, 'H NMR (CDCl3) 5 5,57 (d, J = 3. 9H2, H-1'" ) . 5.44, 5.41 (2d, J - 3.8H2, H-1", H-1') , 4,96 (d, J = 3. 6Hz, H-1) , 2.78-2.58 (m, 4H, 0(C:O) CffaCffa (C: 0) CH3) , 2.18, 2.12, 2.12, 2.09, 2.06, (5s, 15H, 4Ac and 0(C:O)CH2CH2(C:O)CJf3) / 1.21-0.97 (m, 2H, OCHsC/faSi (CH3) 3) , 0.03 (S, 9H, OCH2CH2Si (CHs) 3) .
Anal. Calculated for C5oH84027Si: C, 52.44; H, 7,39. Found: C, 52.29; H, 7.46

Ethyl O-(6-O-acatyl-4-O-lovulinyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(1-4)-[O-(6-O-acetyl-2,3-di-O-m0thyl-α-D-glucopyranosyl)- (1-4)-]2"6"(O-acetyl-2,3-di-O-methyl-1-thio-β-D-glucopyranosida (42).
A solution of imidate 38 (1.10 g, 1.52 mmol) and glycosyl acceptor 36(806 mg, 1,38 mmol) are treated in a 1/2 dichloromethane/ethyl ether mixture (22 ml) according to Method 1. The product is purified by chromatography on silica (2.5/1 and then 3/1 ethyl

acetate/cyclohexane) in order to obtain 42 (1.12 g, 71-,%). [α]D + 95 (c = 1.00, dichloromethane) . ESIMS,
positive mode: m/z, + NaCl, 1111 (M+Na)+; + KF, 1127 {M+K)+, 1H NMR (CDCl3) δ 5.55 (d, J = 3.9Hz, H-1'"), 5.39, 5.37 (2d, J = 3.8 and 3.9 Hz, H-1", H-1'), 4,34 (d, J = 9.7Hz, H-1), 2.84-2.51 (m, 6H, SCH2CH3, 0(C:O)CH2CH2(C:O)CH3) , 2.17, 2.10, 2.09, 2.08, 2.04, (5s, 15H, 4Ac and 0 (C :0) CH2CH2 (C :0) CH3) , 1.30(t,3H, J 7 .4Hz, SCH2CH3) .
Anal. Calculated for C47H76O26S: C, 51.83; H, 7.03; S, 2.94. Found: C, 51.66; H, 7.02; S, 2.94.



PREPARATION 40
2-(trimethylsilyl)ethyl [O-(6-O-acetyl-2,3-di-O-methyl-α-D-glucopyranosyl)- (1-4) -]3-6-O-acetyl-2,3-di-O-methyl-α-D-glucopyranoside (43).
Compound 41 (4.71 g, 4.11 mmol) is reacted as in Preparation 37 in order to obtain, after column chromatography (3/2 cyclohexane/acetone), the deR1vative 43 (4.11 g, 95 %). [α]^ + 154 (c = 0.63,
dichloromethane). ESIMS, positive mode: m/z, + NaCl, 1069 (M+Na)%' + KF, 1085 (M+K)+, 1H NMR (CDCl3) δ 5.46, 5.46 (2d, 3H, J = 3.9Hz, H-1', H-1", H-1'" ) , 4.95 (d, J = 3.5Hz, H-1), 2.81 (d, J = 4.4Hz, OH), 2.11, 2.09, 2.08 (3s, 12H, 4Ac) , 1.19-0.97 (m, 2H, OCH2CH2Si (CH3) 3) . 0.03, (s, 9H, OCH2CH2Si(Cff3)3) .
Anal. Calculated for C45H78025Si: C, 51.61; H, 7.51. Found: C, 51.39; H, 7.54.
PREPARATION 41
2-(trimethylsilyl)ethyl O-(6-O-acetyl-4-O-levulinyl-2,3-di-O-methyl-α-D-glucopyramosyl)-(1-4)-[O-(6-O-acetyl-2 , 3-di-O-methyl-α-D-glucopyranosyl) - (1-4) -] 6~6"* O-acetyl-2,3-di-O-methyl-α-D-glucopyranoside (44).
Thioglycoside 42 (3.86 g, 3.54 mmol) and the glycosyl acceptor 43 (3,60 g, 3.44 mmol) are treated according to Preparation 38. The product is chromatographed (7/2 and then 2/1 dichloromethane/acetone) in order to obtain 44 (5.71 g, 80 %) . [α]D + 161 (c = 0.65, dichloromethane). ESIMS, positive mode: monoisotopic mass = 2072.8, chemical mass = 2074,2, expeR1mental mass = 2074 ± 1 a.m.u. 1H NMR (CDCl3) δ 5.54, (d, J = 3.8Hz, H-1 unit NR) , 5.47-5.40 (m, 6H, H-1), 4.95 (d, J = 3,7H2, H-1 unit R) , 2.84-2.51 (m, 4H, 0 (C :0) CH2CH2 (C :0) CH3) / 2.17, 2.13, 2.12, 2.11, 2.11, 2.08, 2.05 (7s, 27H, 8Ac and 0(C:O)CH2CH2(C:O)Cif3, 1.18-0.97 (m, 2H, OCH2CH2si (CH3) 3) , 0.03 (s, 9H, OCH2CH2Si (CH3) 3) .
Anal. Calculated for C9oH14805iSi: C, 52.12; H, 7.19. Found: C, 51.98; H, 7.25.

PREPARATION 42
2-(trimethylsilyl)ethyl [O-(6-O-acetyl-2,3-di-O-methyl-α-D-glucopyranosyl)- (1-4)-]7-6-O-acetyl-2,3-di-O-methyl-α-D-glucopyranosido (45).
IM Hydrazine hydrate solution in a 3/2 acetic acid/pyR1dine mixture (7.3 ml) is added, at 0°C, to a solution of compound 44 (3.00 g, 1.45 mmol) in pyR1dine (5 ml) . After stirR1ng for 20 minutes, the reaction mixture is evaporated, diluted in dichloromethane (400 ml), washed with aqueous 10 % potassium hydrogen sulphate solution, water, aqueous 2 % sodium hydrogen carbonate solution and water. The solution is dR1ed and concentrated and the residue is chromatographed in order to obtain 45 (2.43 g, 85 %) . [α]D + 167 (c = 0.57, dichloromethane). ESIMS, positive mode: monoisotopic mass = 1974.8, chemical mass = 1976.1, expeR1mental mass = 1975.4 ± 2 a.m.u., 1H NMR (CDCl3) 5 5.47-5.40 (m, 7H, H-1), 4.95 (d, J = 3.7Hz, H-1 unit R) , 2.80 (d, J = 4.4Hz, OH), 2.13, 2.11, 2.10, 2.08, 2.07 (5s, 24H, 8Ac) , 1.18-0.97 (m, 2H, OCH2CH2Si (CH3) 3), 0.03 (s, 9H, OCH2CH2Si (CH3)3) .
Anal. Calculated for C85Hi42049Si: C, 51.66; H, 7.24. Found: C, 51.32; H, 7.26.
PREPARATION 43
2-(trimethylsilyl)ethyl O-(6-O-acetyl-4-0*levulinyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(1-4)-[O-(6-O-acetyl-2,3-di-O-methyl-α-D-glucopyrauiosyl) - (1-4) -]10-6-O-acetyl-2,3-di-O-methyl-α-D-glucopyranoside (46).
Compound 42 (1.35 g, 1.24 mmol) and compound 45 (2.38 g, 1.20 mmol) are treated according to Preparation 38. The residue is chromatographed (4/3 cyclohexane/acetone) in order to obtain 46 (2.56 g, 71%) . [α]D + 166 (c = 0.88, dichloromethane) . ESIMS, positive mode: monoisotopic mass = 3001.3, chemical mass = 3003.2, expeR1mental mass = 3004 ± 1 a.m.u. 1H NMR (CDCl3) δ 5.54, (d, J = 3.8Hz, H-1 unit NR) , 5.47-5.40, (m, lOH, H-1), 4.95 (d, J = 3.7H2, H-1 unit R) , 2.81-2.51 (m, 4H, 0 (C : 0) CH2CH2 (C :0) CH3) , 2.17, 2.13,

2.12, 2.11, 2.11, 2.08', 2.05 {7s, 39H, 12Ac and 0(C:O)CH2CH2(C:O)CH3) , 1.17-0.96 (m, 2H, OCHsCifsSi (CH3) 3) , 0.03 (s, 9H, OCH2CH2Si (CH3) 3) .
Anal. Calculated for Ci3oH2i2075Si: C, 51.99; H, 7.12. Found: C, 51.63; H, 7.12.
PREPARATION 44
(6-O-acetyl-4-O-lovulinyl-2,3-di-O-methyl-α-D-gluco-pyranosyl)-(1-4)~[O-(6-O-acetyl-2,3-di-O-methyl-α-D-glucopyranosyl) - (1-4) -]io-6-O-acatyl-2 ,3-di-O-methyl-a,[3-D-glucopyranosa trichloroacetxmldate (47) .
(a) A solution of glycoside 46 (400 mg, 0.133 mmol) in a 2/1 trifluoroacetic acid/dichloromethane mixture (2 ml) is stirred for 1,5 hours (TLC) . The solution is diluted in a 2/1 toluene/n-propyl acetate mixture (12 ml), concentrated and coevaporated with toluene (5 x 10 ml) . The residue is purified (4/3 acetone/cyclohexane) in order to obtain a solid (364 mg) .
(b) The solid obtained above is dissolved in dichloromethane (2.5 ml). Caesium carbonate (65 mg, 0.200 mmol) and trichloroacetonitrile (63 ml, 0.620 mmol) are added and the mixture is stirred for 2.5 hours and then filtered (Celite), concentrated and purified on a column of silica (50/50/0.1 cyclohexane/acetone/triethylamine) in order to obtain the imidate 47 (348 mg, 86 %) . [α]D + 185 (c = 0.91, dichloromethane). ESIMS, positive mode: monoisotopic mass = 3044.1, chemical mass = 3047.3, expeR1mental mass = 3046.9 ± 0.2 a.m.u. 1H NMR (CD2CI2) 5 8.61, 8.58
(2s, IH, a and P N:H), 6.35 (d, J = 3.7H2, H-la unit R), 5.59, (d, J = 7.5Hz, H-lb unit R) , 5.38 (d, J = 3.8Hz, H-1 unit NR), 5.32-5.25 (m, lOH, H-1), 2.64-2.40 (m, 4H, 0{C:O)CH2CH2{C:O)CH3) , 2.02, 1.96, 1.95, 1.94, 1.93, 1,89 (6s, 39H, 12Ac and 0 (C:O) CH2CH2 (C:O) CH3) .
Anal. Calculated for C127H200CI3NO25: C, 50.06; H, 6.61; N, 0.46. Found: C, 49.93; H, 6.52; N, 0.42.



PREPABATION 45
(6-O-acetyl-4-O-levulinyl-2,3-di-O-methyl-α-D-gluco-pyranosyl)-(1-4)-[O-(6-O-acetyl-2,3-di-O-methyl-α-D-glucopyranosyl) - (1-4) -] 2-6-O-acotyl-2 , 3-di-O-methyl-α, p-D-glucopyranose trichloroacatimidate (48).
Compound 41 (200 mg, 0.174 mmol) is treated according to Preparation 4 4. The reaction mixture is purified on a column of silica (3/2 toluene/acetone) in order to obtain the imidate 48 (230 mg, 77 %). ESIMS, positive mode: m/z, + NaCl, 1210 (M+Na) ^; + KF, 122 6 (M+K)+, 1H NMR (CDCl3) 5 8.66-8. 64 (2s, IH, a and p N:H), 6.51 (d, J = 3.6Hz, H-lp) , 5.71 (d, J = 7.5Hz, H-lp) , 2.9O-2.52 (m, 4H, 0 (C :0) CH2CH2 (C : 0) CH3) , 2.17, 2.11, 2.11, 2.09, 2.05 (5s, 4 Ac and 0{C:O)CH2CH2(C:O)CH3) .
PREPARATION 46
Mathyl O- (6-O-acatyl-4-O-levulinyl-2 , 3-di-O-methyl-α-D-glucopyranosyl) - (1-4) -[O- (6-"O-acotyl-2,3-di-O-methyl-α-D-glucopyranosyl) - (1-4) -] 2-O- (benzyl-2,3-di-O-methyl-β-D-glucopyranosyluronata)-(1-4)-O-(3,6-di-O-acatyl-2-O-benzyl-α-D-glucopyranoayl)-(1-4)-O-(benzyl-2,3-di-O-mothyl-α-L-ido-pyranosyluronate)-(1-4)-2,3,6-tri-O-benzyl-α-D-glucopyranosida (49) .
The imidate 48 (73 mg, 0.061 mmol) and the glycosyl acceptor 26 (82 mg, 0.059 mmol) are treated according to Preparation 39. The compound is purified on a Sephadex LH-20 chromatography column (1/1
dichloromethane/ethanol) and then on a column of silica
(3/1 toluene/acetone) to give the deR1vative 49 (98 mg,
69 %) . [α]D + 95 (c = 1.01, dichloromethane) . ESIMS,
positive mode: monoisotopic mass = 2414.97, chemical
mass = 2416.97, expeR1mental mass = 2416.2. 1H NMR
(CDCl3) 5 7.43-7.20 (m, 30H, 6Ph), 5.55 (d, J = 3.9H2,
H-1 unit NR), 5.50 (d, J = 3.9Hz, H-1 unit NR-3), 5.44,
5.38 (2d, J = 3.7 and 3.9Hz, H-1 unit NR-1, unit NR-2),
5.29 (d, J = 6.8H2, H-1 unit R-1), 5.17 (d, J = 3.5Hz,
H-1 unit R-2), 4.56 (d, J - 3.7H2, H-1 unit R) , 4.10
(d, J = 7.9Hz, H-1 unit R-3), 2.81-2.50 (m, 4H,

0(C:O)CH2CH2(C:O)CH3) , 2/l7, 2.15, 2.11, 2.09, 2.05, 2.00 (7s, 21H, 6Ac and 0 (C : 0) CH2CH2 (C : 0) CH3) .
Anal. Calculated for C120H158CI3O51: C, 5 9.63; H, 6.59. Found: C, 59,23; H, 6.58.
PREPARATION 47
Methyl[O-(6-O-acetyl-2,3-di-O-methyl-α-D-glucopyrano-syl) - (1-4) -] 3"O- (benzyl-2 , 3-di-O-methyl-β-D-glucopyrano-syluronate)-(1-4)-O-(3,6-di-O-acetyl-2-O-benzyl-α-D-glucopyranosyl)-(1-4)-O-(banzyl-2,3-di-O-methyl-α-L-idopyranosyluronato)-(1-4)-2,3,6-tri-O-benzyl-α-D-glucopyranosidtt (50).
The octasaccharide 49 (120 mg, 0.050 mmol) is
reacted as in Preparation 37. The residue is purified
on a column of silica (3/1 toluene/acetone) in order to
obtain compound 50 (95 mg, 83 %) . [α]D + 80 (C = 0.62,
dichloromethane). ESIMS, positive mode: monoisotopic
mass = 2316.9, chemical mass = 2318.4, expeR1mental
mass = 2318.2 ± 0.4 a.m.u. 1HNMR (CDCl3) δ 7.42-7.12
(m, 30H, 6Ph), 5.50, 5.46, 5.43, 5.40 (d, J = 3.9, 3.9,
3.7, 3.7Hz,
H-1 unit NR, unit NR-1, unit NR-2, unit NR-3) , 2.14, 2.10, 2.09, 2.08, 2.00, 1.88 (6s, 18H, 6Ac).
Anal, Calculated for C115H152O49: C, 5 9.57; H, 6.60. Found: C, 59.49; H, 6.61.



PREPARATION 48
Methyl O-(6-O-acetyl-4-O-levulinyl-2,3-di-O-methyl-α-D-glucopyranosyl) - (1-4)-[O-(6-O-acetyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(1-4) -] 15-O- (benzyl-2,3-di-O-methyl-β-D-glucopyranosyluronata)-(1-4)-O-(3,6-di-O-acetyl-2-O-benzyl-α-D-glucopyranosyl)-(1-4)-O-(benzyl-2,3-di-O-methyl-α-L-ido-pyrauiosyluronate)-(1-4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (51).
The imidate 47 (84 mg, 0.027 mmol) is treated with the glycosyl acceptor 50 (62 mg, 0.027 mmol) according to Preparation 39. The residue is first purified on a column of Toyopearl HW-4 0 and then on a
column of silica (1/1 cyclohexane/acetone) in order to obtain the deR1vative 51 (71 mg, 51 % not optimized) . [α]D + 136 (c = 0.95, dichloromethane) . ESIMS, positive mode: monoisotopic mass = 5200.11, chemical mass = 5203.39, expeR1mental mass = 5203.5. 1H NMR (CDCl3) δ 7.42-7.18 (m, 30H, 6Ph) , 5.54 (d, J = 3.8Hz, H-1 unit NR) , 5.51-5.40 (m, 15 H-1), 5.30 (d, J = 6.8Hz, H-1 unit R-1), 5.17 (d, J = 3.5Hz, H-1 unit R-2), 4.56 (d, J = 3.7Hz, H-1 unit R), 4.09 (d, J = 7.9Hz, H-1 unit R-3) , 2.85-2.53 (m, 4H, 0 (C:O) CH2CH2 (C:O) CH3) , 2.17, 2.16, 2.13, 2.11, 2.08, 2.05, 2.00, 1.88 (8s, 57H, 18Ac and
0(C:O)CH2CH2(C:O)CH3) .
Anal. Calculated for C24oH350O123.4H2O: C, 54.64 ; H, 6.84. Found: C, 54.51; H, 6.79.



PREPARATION 49
Ethyl O- (4 , 6-O-β-inethoxybenzylidene-α-D-glucopyrano-
syl)-(1-4)-l-thio-β-D-glucopyrano3ide (53).
Anisaldehyde dimethyl acetal (35.8 ml, 0.21 mol) and camphorsulphonic acid (4.44 g, 19,1 mmol) are added, at +5°C and under argon, to a solution of compound 52 (73.89 g, 0.19 mmol) (W.E. Dick Jr et J.E. Hodge, Methods in Carbohydrate Chemistry, 7, 1976, 15-18) in a 3.5/1 acetonitrile/N,N-dimethylformamide mixture (990 mmol) . After stirR1ng for 1.5 hours at room temperature, the mixture is neutralized by addition of triethylamine (2.96 ml, 21.0 eq.). The mixture is concentrated and the syrup is purified on a column of silica (100/0 and then 50/50 dichloromethane/methanol) in order to obtain 53 (58.6 g, 61 %, not optimized). [α]D + 47 (c = 1.03, methanol). ESIMS, positive mode: m/z, 503 (M-H)'. 1H NMR (CD3OD) 5 7,41, 6.89 (2d, 4H, CH3OC6/f4) / 5.51 (s, CHC34) f 5.20 (d, J = 3.6Hz, H-1'), 4.39 (d, J = 7.1Hz, H-1) , 3.7 8 (s, 3H, Cff30C6H4) , 2.75 (q, 2H, J = 7.0Hz, SCH2CH3) , 1.29 (t, 3H, SCH2Cff3) .
Anal. Calculated for C22H32O11S: C, 52.37; H, 6.39; S, 6.35. Found: C, 52.15; H, 6,61; S, 5.84.
PREPARATION 50
Ethyl O- (2,3-di-O-aceyl-4,6-β-mathoxybenzyliden«-α-D-glucopyranosyl)-(1-4)-2,3,6-tri-O-acetyl-l-thio-β-D-glucopyranoside (54).
triethylamine (65 ml, 0.47 mol) and acetic anhydride (89 ml, 0.94 mol) are added dropwise, at 0°C, to a suspension of 53 (47.22 g, 93.6 mmol) in dichloromethane (450 ml) . 4-DimethylaminopyR1dine (5.71 g, 46.8 mmol) is then added and the mixture is left stirR1ng for 1.5 hours at room temperature. The reaction is stopped by addition of methanol (45 ml, 1.12 mol) and then washed successively with cold aqueous 10 % potassium hydrogen sulphate solution, water, saturated sodium hydrogen carbonate solution and water. The solution is dried, concentrated and

crystallized (cyclohexanethyl acetate) in order to obtain 54 (64.9 g, 97 %). [α]o +21 (c = 1.00, dichloromethane) . pf 213-"215°C. ESIMS, positive mode: m/z + NaCl, 737 (M+Na)+, + KF, 753 (M+K)+, 1H NMR (CDCl3) δ 7,34, 6.86 (2d, 4H, CH3OCSH4) , 5.43 (s, CHC1H^) , 5.34 (d, J = 4.1Hz, H-1'). 4.54 (d, J = 9.9Hz, H-1), 3.78 is, 3H, CH3OCSH4) ,2.7 4-2.60 (m, 2H, SCffaCHa) , 2.10, 2.06, 2.03, 2.01 (4s, 15H, 5Ac) , 1.26 (t, 3H, SCH2Cif3) •
Anal. Calculated for C32H42O16S: C, 53.78; H, 5.92; S, 4.49. Found: C, 53.74; H, 6.08; S, 4.40.
PREPARATION 51
Ethyl O- (2,3-di-O-acotyl-4-β-mathoxybenzyl-α-D-gluco-
pyranosyl)-(1-4)-2,3,6-tri-O-acetyl-l-thio-β-D-gluco-
pyranoside (55) and ethyl O-(2,3-di-O-acotyl-4-β-
methoxybanzyl-α-D-gluGopyranosyl)-(1-4)-2,3-di-O-
acotyl-1-thio-β-D-glucopyranoside (56).
A suspension of 54 (25.0 g, 35.0 mmol),
borane/trimethylamine complex (20.4 g, 0.28 mol) and
molecular sieves (33 g, 4A) is stirred for 1 hour under
argon in toluene (810 ml). The mixture is cooled to 0*C
and aluminium chloR1de (14.0 g, 0.11 mol) is added
slowly. The reaction medium is stirred for 25 minutes
(TLC), poured into cold, aqueous 20 % potassium
hydrogen sulphate solution, stirred for 1 hour at 0°C
and then filtered (Celite) • The organic phase is washed
with water, with aqueous 2 % sodium hydrogen carbonate
solution, with water, dried and concentrated. The
ft
residue is purified on a column of silica in order to obtain 55 (7.37 g, 29 %, not optimized) and 56 (1.36 g, 6 %). An analytical sample of 55 is crystallized from a cyclohexane/ethyl acetate mixture, [α]D +30 (c = 1.00, dichloromethane) . m.p. 151-153o
C ESIMS, positive mode: m/z, + NaCl, 739 (M+Na)+, + KF, 755 (M+K)*. 1H NMR (CDCl3) δ 7.19, 6.87 {2d, 4H, CH3OC6H4) , 5.36 (d, J = 3.5Hz, H-1'), 4.54 (s, 2H, C6H4CH2) , 4.53 (d, J = 9.0Hz, H-1) , 2.7 O-2.65 (m, 2H, SCH2CH3) .
Anal. Calculated for C32H42O16S: C, 53.62; H, 6.19; S, 4.47. Found: C, 53.57; H, 6.21; S, 4.43,

Compound 56: [α]D + 19 (c = 1.11, dichloro-methane). ESIMS, positive mode: m/z + NaCl, 697 (M+Na)+, + KF, 713 (M+K)-. -H NMR (CDCl3) δ 7.17, 6.84 (2d, 4K, CH3OC5HJ , 5.3 6 (d, J = 4.5Hz, H-1' ) , 4.54 (d, J = IO.IH2, H-1) , 4 .49 (s, 2H, C6.CH2 , 2.69-2.64 (m, 2H, SCH2CH3) , 2.02, 2.01, 2.00, 1.96 (4s, 12H, 4Ac) , 1.2 5 (t, 3H, SCH2CH3) .
Anal. Calculated for C30CH42Os40; H, 6.27; S, 4.75. Found: C, 53.29; H, 6.39; S, 4.53.
PREPARATION 52
Ethyl O- (2,3-tri-O-acetyl-4-β-methoxybenzyl-α-D-gluco-pyranosyl)-(1-4)-2,3,6-tri-O-acetyl-l-thio-β-D-gluco-pyranoside (57).
Acetic anhydride (1.47 ml, 15.5 mmol) is added, at 0°C, to a mixture of 55 (5.6 g, 7.77 mmol), triethylamine (1.19 ml, 8,54 mmol) and 4-dimethylamino-pyR1dine (190 mg, 1.55 mmol) in dichloromethane (40 ml) . After stirR1ng for 40 minutes (TLC) at room temperature, the mixture is diluted with dichloromethane (50 ml) and washed with cold, aqueous 10 % potassium hydrogen sulphate solution, water, saturated sodium hydrogen carbonate solution and water. The solution is dried and concentrated and the residue is purified on a column of silica (35/65 ethyl acetate/cyclohexane) in order to obtain 57 (5.66 g, 96 %) . [α]D 44 (c = 1.03, dichloromethane). ESIMS, positive mode: m/z, + NaCl, 781 (M+Na) +, + KF, 7 97 (M+K)+, 'H NMR (CDCl3) δ 7.15, 6.85 (2d, 4H, CU,0C,HJ , 5.30 (d, J = 4.2Hz, H-1'), 4.53 (d, J = lO.OHz, H-1), 2.6 9-2.64 (m, 2H, SCH2CH3) , 2.09, 2.07, 2.04, 2.01, 2.00, 1.98 (6s, 18H, 6Ac) , 1.25 (t, 3H, SCH2CH3) .
Anal. Calculated for C34H46O17S. 52.82; H, 6.11; S, 4.22. Found: C, 53,77; H, 6.24; S, 4.09.


PREPARATION 53
Ethyl 4,6-O-benzylidene-2,3-di-O-methyl-l-thio-β-D-
glucopyranoside (59).
Sodium hydride (500 mg, 19.9 mmol) is added, at 0°C, to a mixture of compound 58 (2.59 g, 8.29 mmol) (A.F. Bochkov et al. , Izv. Akad. Nauk SSSR, Ser. Khim. (1968) , (1) , 179) and methyl iodide (1.70 ml, 19.9 mmol) in N,N-dimethylformamide (25 ml) and the mixture is allowed to return to a temperature of 20oC. The mixture is left stirR1ng for 30 minutes (TLC) and methanol is then added. The mixture is poured into water and extracted with ethyl acetate. The organic phase is washed successively with aqueous IM sodium thiosulphate solution and water, dried and concentrated. The residue is triturated in ethyl ether in order to obtain 59 (0.42 g, 15 %) ; purification of

the mother liquors on a column of silica (12/1 toluene/acetone) followed by crystallization allows an additional fraction of 59 (1.6 g, overall yield: 71 %) to be obtained, m.p.: 108°C. [α]D - 78 (c = 1.00, dichloromethane). LSIMS, positive mode: m/z thioglycerol + NaCl, 363 (M+Na)+,- thioglycerol + KF, 379
(M+K)+, 1H NNR (CDCl3) 5 7.51-7.33 (m, 5H, Ph) , 5.52 (s, IH, CgHsCH) , 4.45 (d, IH, J = 9.8Hz, H-1) , 3.64
(s, 3H, OCH3) , 3.62 (s, 3H, OCH3) , 2.78-2.68 (m, 2H, SCH2CH3) , 1.31 (t, 3H, J = 2.7Hz, SCH2CH3) .
Anal. Calculated for C17H24O5S (340.44) : C, 59,98; H, 7.11; S, 9.42. Found: C, 59.91; H, 7.15; S, 8.96.
PREPARATION 54
2-(trimethylsilyl)ethyl 4,6-O-benzylidene-2,3-di-O-
methyl-α-D-glucopyranoside (60).
Compound 59 (23.0 g, 67.5 mmol) and 2-
(trimethylsilyl)ethanol (19.4 ml, 135 mmol) are dissolved in a 2/1 mixture of ethyl ether and dichloromethane (345 ml) and 4 A molecular sieves (11 g) are added. The mixture is left stirR1ng for 1 hour at 25°C and N-iodosuccinimide (49.7 g, 220 mmol) is added, followed, at 0°C, by silver triflate (2.20 g, 8.78 mmol). The mixture is left stirR1ng for 20 minutes
(TLC), and solid sodium hydrogen carbonate is then added. The mixture is diluted with dichloromethane, filtered through Celite, washed successively with aqueous IM sodium thiosulphate solution and water, dried and evaporated to dryness. The residue is purified on a column of silica (15/1 and then 5/1 cyclohexane/ethyl acetate) in order to obtain 60p
(4.20 g, 15 %) and 60a (8.40 g, 31 %) .
Compound 60a. [α] D + 96 (c = 0.4, dichloromethane) . ESIMS, positive mode: m/z, 419 (M+Na)+; 435
(M+K)+, 1H NMR (CDCl3) 5 7.52-7.35 (m, 5H, Ph) , 5.54 (s, IH, CgHsCH) , 4.98 (d, IH, J = 3. 7Hz, H-1) , 3.64
(s, 3H, OCH3) , 3.62 (s,3H, OCH3) , 1.24-0.96 (m, 2H, OCH2CH2Si(CH3)3) , 0.00 (s, 9H, OCH2CH2Si (CH3) 3) .

Anal. Calculated for C20H32O6 (396.56) : C, 60.58; H, 8.13. Found: C, 60.26; H, 8.39.
PREPARATION 55
2-(trimethylsilyl)ethyl 6-O-benzyl-2,3-di-O-methyl-α-D-
glucopyranoside (61).
Compound 60 (21.1 g, 53.3 mmol) is dissolved in dichloromethane (154 ml). triethylsilane (34 ml, 213 mmol) is added at room temperature, followed by dropwise addition of a mixture of trifluoroacetic acid (16.3 ml, 213 mmol) and trifluoroacetic anhydride (0.49 ml, 3.47 mmol). The mixture is left stirR1ng for 2 hours and aqueous IM sodium hydroxide solution is added until the pH is basic. After separation of the phases by settling, the aqueous phase is extracted with ethyl acetate and the organic phases are then combined, dried and concentrated. The residue is purified on a column of silica (14/1 and then 12/1 dichloromethane/acetone) in order to obtain 61 (12.5 g, 59 %) . [α]D + 100 (c = 1.45, dichloromethane). 'H NMR 6 7.4O-7.20 (m, 5H, Ph) , 4.98 (d, IH, J = 3. 5Hz, H-1) , 3.62 (s, 3H, OCH3) , 3.4 9 (s, 3H, OCH3) , 1.14-0.91 (m, 2H, CH2CH2Si(CH3)3) , 0.00 (s, 9H, CH3CH3Si (CH3) 3) .
Anal. Calculated for C2oH3o06Si (398.58) : C, 60.27; H, 8.60. Found: C, 60.18; H, 8.81.
PREPARATION 56
2-(trimethylsilyl)ethyl O-(2,3,6-tri-O-acetyl-4-O-β-methoxybenzyl-α-D-glucopyranosyl) - (1-4)-O- (2,3,6-tri-O-acetyl-β-D-glucopyranosyl-(1-4)-6-O-benzyl-2,3-di-O-methyl-α-D-glucopyranoside (62).
A mixture of thioglycoside 57 (19.1 g, 25.1 mmol) and the glycosyl acceptor 61 (7.5 g, 18.7 mmol) is treated according to Method 3 in order to obtain, after purification on a column of silica (20/1 and then 10/1 dichloromethane/acetone), 62 (19.7 g, 95 %). [α]d +90 (c = 1.15, dichloromethane).
Anal. Calculated for C52H74023Si (10 95.24) : C, 57.03; H, 6.81. Found: C, 57.33; H, 6.85.















pyranosyl) - (1-4) ] 3-6-O-ben^yl-2, 3-di-O-methyl-a, p-D-glucopyranose (71) .
Compound 70 (876 mg, 0.41 mmol) is treated as in Preparation 44(a). The residue is purified on a column of silica in order to obtain a mixture of isomers (a/b = 60/40) of 71 (600 mg, 50 % over the two steps). [α]D +89 (c = 0.74, dichloromethane). ESIMS, positive mode: monoisotopic mass = 2028.97, chemical mass = 2 03 0.24, expeR1mental mass = 2030.19 ± 0.09 a.m.u. 1H NMR (CDCl3) δ 7.33-7.32 (m, 5H, Ph) , 5.65 (d, 3H, J = 3.8Hz H-1 unit NR, unit NR-2 and unit C) , 5.63 (d, IH, J = 3.8Hz, H-1 unit R-2), 5.33 (d, IH, J = 3.2Hz, H-la unit R) , 5.02 (t, IH, J = lO.lHz, H-4 unit NR), 4.59 (d, IH, J = 5.3Hz, H-lp unit R), 4.32 (d, IH, J = 7.9Hz, H-1 unit NR-1) , 4.30 (d, 2H, J = 7.9Hz, H-1 unit NR-3 and unit R-3) , 4.29 (d, IH, J = 7.9H2, H-1 unit R-1) , 2.8 O-2.50 (m, 4H, 0 (C:O) CH2CH2 (C:O) CH3) , 2.18 (s, 3H, 0(C:O)CH2CH2(C:O)CH3) .
PREPARATION 66
O- (4-O-Levulinyl-2,3,6-tri-O-methyl-α-D-gluco-pyranosyl) - (1-4) -O- (2, 3, 6-tri-O-methyl-β-D-gluco-pyranosyl) - (1-4) - [O- (2,3, 6-tri-O-methyl-α-D-gluco-pyranosyl)-(1-4)-O-(2,3,6-tri-O-methyl-β-D-gluco-pyranosyl) - (1-4) ] 3-6-O-benzyl-2, 3-di-O-methyl-α,β-D-glucopyranose trichloroacetlmidate (72).
To a solution of 71 (593 mg, 0.29 mmol) in dichloromethane (7 ml) are added potassium carbonate
(72.2 mg, 0.52 mmol) and trichloroacetonitrile (176 )il, 1.75 mmol) . The mixture is left stirR1ng for 16 hours, filtered and evaporated. The residue is filtered through silica gel (5/4 cyclohexane/acetone + 1 %o of triethylamine) in order to obtain a mixture of the anomers (a/p = 47/53) of the imidate 72 (414 mg, 46 %).
[α]D + 86 (c = 0.84, dichloromethane). 'H NMR (CDCl3) δ 7.33-7.32 (m, 5H, Ph) , 6.50 (d, IH, J = 3.5Hz, H-la unit R) , 5.65 (d, IH, J = 8.2Hz, H-lp, unit R) , 5.65
(d, IH, J = 3.8Hz, H-1 unit NR) , 5.64 (d, 2H, J = 3.8Hz, H-1 unit R-2 and unit C) , 5.61 (d, IH, J =

3.8Hz, H-1 unit R-2), 5.02 (t, IH, J = lO.lHz, H-4 unic NR; , 4.37 (d, IH, J = 7. 9Hz, H-1 unit R-1) , 4.30
(d, 3H, J = 7.9Hz, H-1 unit NR-1, unit NR-3 and unit R-3) , 2.8O-2.50 (m, 4H, 0 (C :0) CH2CH2 (C :0) CH3) , 2.18
(s, 3H, 0(C:O)CH2CH2(C:O)CH3) .



PREPARATION 61
Methyl O-(4-O-levulinyl-2,3,6-tri-O-methyl-α-D-gluco-pyranosyl) - (1-4)- [O-(2,3,S-tri-O-methyl-α-D-glucopyrano-syl)-(1-4)-O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl) - (1-4) ] 3-O- (6-O-benzyl-2, 3-di-O-inethyl-α-D-glucopyranosyl)-
(1-4)-O-(benzyl 2,3-di-O-methyl-β-D-glucopyranosyl-uronate)-(1-4)-O-(3,6-di-O-acetyl-2-O-benzyl-α-D-gluco-pyranosyl)-(1-4)-O-(benzyl 2,3-di-O-methyl-α-L-ido-pyranosyluronate)-(1-4)-2,3,6-tri-O-benzyl-α-D-gluco-pyranoside (73).
The glycosyl acceptor 26 (220 mg, 0.16 mmol) and imidate 72 (344 mg, 0.16 mmol) are dissolved in a 1/2 dichloromethane/ethyl ether mixture (5 ml) . 4 A molecular sieves (750 mg/mmol) are added and the mixture is left stirR1ng at 25°C for 1 hour. The mixture is cooled to -25°C and a IM solution of tert-butyldimethylsilyl triflate in dichloromethane (0.20 mol/mol of imidate) is added. After stirR1ng for 15 minutes, solid sodium hydrogen carbonate is then added and the mixture is filtered and concentrated. The residue is placed on a column of Toyopearl® HW-50 (1/1 dichloromethane/ethanol) and the fraction containing the glycosyl acceptor is returned to the reaction and then treated as above. Successive purifications are carR1ed out on a column of silica (5/4 and then 1/1 toluene/acetone) in order to obtain a fraction 73a/(3 = 7/3 (107 mg) and a fraction in 73a/P = 9/1 (201 mg) in an overall yield of 57 % (308 mg) . 'H NMR (CDCl3) 6 7.33-7.25 (m, 35H, 7Ph) , 5.65 (d, 3H, J = 3 . 5Hz, H-1 unit A, unit C and unit E), 5.57 (d, IH, J = 3.9Hz, H-1 unit G) , 5.52 (d, IH, J = 3.3Hz, H-1 unit I) , 5.2 9 (d, IH, J = 6.8Hz, H-1 unit L), 5.17 (d, IH, J = 3.5Hz, H-1 unit K), 4.56 (d, IH, J = 3.5Hz, H-1 unit M), 4.31 (d, 3H, J = 7.9Hz, H-1 unit B, unit D and unit F) , 4.27 (d, IH, J = 8.0Hz, H-1 unit H), 4.08 (d, IH, J = 8.0Hz, H-1 unit J) , 2.8O-2.50 (m, 4H, 0 (C :0) CH2CH2 (C:O) CH3) , 2.18 (s, 3H, 0(C:O)CH2CH2(C:O)CH3) , 1.97 (s, 3H, Ac) , 1.81 (s, 3H, Ac).



PREPARATION 68
Methyl [O-(2,3,6-tri-O-methyl-α-D-glucopyranosyl)-(1-4) -O- (2,3,6-tri-O-methyl-β-D-glucopyranosyl) - (1-4)] 4-O-(6-O-benzyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(benzyl 2,3-di-O-methyl-β-D-glucopyranosyluro-nate)-(1-4)-O-(3,6-di-O-acetyl-2-O-benzyl-α-D-glucopyrano-syl) - (1-4) -O- (benzyl 2, 3-di-O-methyl-α-L-idopyranosyl-uronate)-(1-4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (74).
Compound 73 (130 mg, 38.2 μmol) is treated according to Method 2 and the crude product is purified on a column of silica in order to obtain 74 (118 mg, 93 %) . [α]D + 78 (c = 0.48, dichloromethane) ; ESIMS, positive mode: monoisotopic mass = 3301.49; chemical mass = 3303.65; expeR1mental mass = 3302.40 a.m.u. 1H NMR (CDCl3) δ 7.33-7.25 (m, 35H, 7Ph) , 5.64 (d, 3H, J = 3.5Hz, H-1 unit A, unit C and unit E), 5.57 (d, IH, J = 3.9Hz, H-1 unit G) , 5.52 (d, IH, J ^ 3.3Hz, H-1 unit I), 5,29 (d, IH, J = 6.8Hz, H-1 unit L), 5.17 (d, IH, J = 3.5Hz, H-1 unit K), 4.56 (d, IH, J = 3.5Hz, H-1 unit M), 4.31 (d, 3H, J = 7.9Hz, H-1 unit B, unit D and unit F), 4.27 (d, IH, J = 8.0Hz, H-1 unit H), 4.08 (d, IH, J = 8.0Hz, H-1 unit J), 1.97 (s, 3H, Ac), 1.81 (s, 3H, Ac).
PREPARATION 69
Methyl O-(2,6-di-O-benzyl-4-O-levulinyl-3-O-methyl-α-D-glucopyrauiosyl)-(1-4)-O-(2-O-acetyl-6-O-benzyl-3-O-methyl-β-D-glucopyranosyl)-(1-4)-O-(2,6-di-O-benzyl-3-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(2-O-acetyl-6-O-benzyl-3-O-methyl-β-D-glucopyranosyl)-(1-4)-[O-(2,3,6-tri-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl)- (1-4)]^-O- (6-O-benzyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(benzyl 2,3-di-O-methyl-β-D-glucopyranosyluronate)-(1-4)-O-(3,6-di-O-acetyl-2-O-benzyl-α-D-glucopyranosyl)-(1-4)-O-(benzyl 2,3-di-O-methyl-α-L-idopyranosyluronate-(1-4)-2,3,6-tri-O-benzyl-α-D-glucopyranoside (75).

The glycosyl acceptor 74 (112 mg, 33-9 inethylmol) and the imidate 17 (59.1 mg, 37.2 inethylmol) (see Preparation 16) are dissolved in toluene (2 ml) , 4 A molecular sieves (42 mg) are added and the mixture is left stirR1ng at 25°C for 1 hour- The mixture is cooled to -20oC and a IM solution of tert-butyldimethylsilyl triflate in toluene (0,20 mol/mol of imidate) is added. After stirR1ng for 15 minutes, solid sodium hydrogen carbonate is then added and the mixture is filtered and concentrated, The residue is placed on a column of Toyopearl® HW-50 (1/1 dichloromethane/ethanol) and the fraction containing the acceptor and the 17-mer is returned to the reaction and treated as above. The product is purified successively on a column of Toyopearl, HW-50 and on a column of silica in order to obtain 75 (71 mg, 44 %) , [α] D + 80 (c = O-26, dichloromethane). ESIMS, positive mode: monoisotopic mass == 4728.10; chemical mass = 4731.26; expeR1mental mass = 4731-27 ± 0.39 a.m,u. 1H NMR (CDCl3) S of the main anomeR1c protons: 5.64; 5.57; 5,52; 5.48; 5,47; 5,29; 5.17; 4,56; 4.50; 4.29; 4.27; 4.08 ppm.



PREPARATION 70
Methyl 2,3-di-O-methyl-S-O-tert-butyldimethylsilyl-α-D-glucopyranoside (77) .
Tert-butyldimethylsilyl chloride (14.0 g, 92.9 mmol), triethylamine (15 ml, 108 mmol) and 4-dimethylaminopyridine (2G0 mg, 2.13 mmol) are added, under argon, to a solution of 76 (D. trimmell, W.M. Doane, C.R. Russel, C.E. R1st, Carbohydr. Res,, (1969) 11, 497) (15.84 g, 71.3 mmol) in dichloromethane (300 ml) . After stirR1ng for 15 hours at room temperature, the solution is diluted with dichloromethane, washed with saturated aqueous sodium hydrogen carbonate solution, dried (magnesium sulphate), filtered and concentrated. The residue is purified by flash chromatography (1.3/1 cyclohexane/ethyl acetate) in order to obtain 77 (22.79 g, 95 %) in the form of a colourless syrup, [α]+ +87 (c = 1.2, chloroform).
PREPARATION 71
Methyl 2,3-di-O-methyl-6-O-tert-butyldimethylsilyl-α-D-
xylo-4-hexulopyranoside (78).
A solution of dimethyl sulphoxide (8.7 ml, 123 mmol) in dichloromethane (20 ml) is added, under argon and at -70oC, to a solution of oxalyl chloride
(5.4 ml, 61.9 mmol) in dichloromethane (120 ml). After 15 minutes, a solution of 77 (18.78 g, 55.8 mmol) in dichloromethane is added dropwise. After magnetic stirR1ng for 15 minutes, triethylamine (37 ml, 265 mmol) is added and, after 15 minutes, the mixture is allowed to return to room temperature. Water (150 ml) is added and the aqueous phase is extracted with dichloromethane (150 ml) . The organic phases are combined, washed with saturated aqueous sodium chloride solution, dried (magnesium sulphate) and concentrated. The residue is purified by flash chromatography (9/1 and then 4/1 cyclohexane/ethyl acetate) in order to obtain 78 (17.3 g, 93 %) in the form of a colourless oil. [α]D + 98 (c = 1.0, chloroform).

PREPARATION 72
Methyl 4-deoxy-2,3-di-O-methyl-4-C-methylene-6-O-tert-
butyldimethylsilyl-α-D-xylo-hexapyranoside (79).
A 1.6 M solution of n-butyllithium in n-hexane (75 ml) is added dropwise, under argon, to a suspension of methyltriphenylphosphonium bromide (43.3 g, 127 mmol) in tetrahydrofuran (250 ml). After 30 minutes at room temperature, the mixture is cooled to -70°C. A solution of 78 (13.97 g, 41.8 mmol) in tetrahydrofuran (60 ml) is then added. After 30 minutes at -70°C, the mixture is allowed to return to room temperature. After 1 hour, saturated aqueous ammonium chloride solution (3 00 ml) is added and the aqueous phase is extracted with ether. The organic phase is dried (magnesium sulphate), filtered and concentrated. The residue is purified by flash chromatography (7/1 and then 4/1 cyclohexane/ethyl acetate) in order to obtain 79 (8,30 g, 60 %) in the form of a colourless oil, [α] D + 151 (c = 1.3, chloroform).
PREPARATION 73
Methyl 4-deoxy-2,3-di-O-methyl-4-C-methylene-α-D-xylo-
hexapyranoside (80).
Camphorsulphonic acid (pH 1) is added to a solution of 79 (8.50 g, 25.6 mmol) in a 5/1 dichloromethane/methanol mixture (250 ml) . After complete disappearance of the starting mateR1al (TLC, l/l cyclohexane/ethyl acetate), the solution is neutralized by addition of triethylamine. After concentrating, the residue is purified by flash chromatography (1/1 and then 1/2 cyclohexane/ethyl acetate) to give 80 (5.32 g, 95 %) in the form of a colourless syrup, [α]D + 239 (c = 1.0, chloroform),
PREPARATION 74
Phenyl 2,4,6-tri-O-acetyl-3-O-methyl-l-seleno-β-D-
glucopyranoside (83).
Method I: Selenophenol (5.7 ml, 53.7 mmol) is added to a solution of 81 (E.L. Hirst, E. Percival,

Methods Carbohydrate Chem, (1963) 2, 145) (l/l mixture of anomers: 13.05 g, 36.0 mmol) in dichloromethane
(120 ml) under argon. The reaction medium is cooled to 0oC and 48 % trifluoroborane diethyl etherate solution
(8.3 ml, 71.9 mmol) is added dropwise. After 3 hours at room temperature, the reaction mixture is diluted with dichloromethane (100 ml) , washed with saturated aqueous sodium hydrogen carbonate solution, dried (magnesium sulphate), filtered and concentrated. The crude compound 83 (8.17 g, 68 %) from 81) is used directly in the deacetylation reaction,
Method 2: Sodium borohydride (510 mg,
14.6 mmol) is added, at 0°C and under argon, to a
suspension of diphenyl diselenide (2.27 g, 7.27 mmol)
in ethanol. A further portion of trifluoroborane
diethyl etherate is added if the reaction medium has
not lost its oR1ginal yellow colour within 15 minutes.
This solution is transferred under argon to a solution
of 82 (A.K. Sen, K.K. Sakar, N, Banerji, J. Carjbohydr.
Chem., (1988) 7, 645) (4.22 g, 11.0 mmol) in
dichloromethane (25 ml) . After refluxing for 3 hours, the mixture is left to cool to room temperature, the sodium bromide is filtered off and the filtrate is concentrated. The residue is dissolved in dichloromethane (100 ml) and washed with aqueous IM sodium hydroxide solution (50 ml) and saturated aqueous ammonium chloride solution (50 ml). The aqueous phases are extracted with dichloromethane (20 ml) and the organic phases are dried (magnesium sulphate), filtered and concentrated. The residue is purified by flash chromatography (1.7/1 cyclohexane/ethyl acetate) and then crystallized from ethyl acetate in order to obtain 83 (4.35 g, 86 %) . m.p. 101-102°C. [α]D - 20 (c = 1.0, chloroform).
PREPARATION 75
Phenyl 3-O-methyl-l-seleno-β-D-glucopyranoside (84)•
The crude compound 83 obtained from 82 (32.3 g, 84.3 mmol) is dissolved in methanol (500 ml)

ana soaium (l. 2 g) is mt/toduced slowly. After 1 hour, the solution is neutralized by addition of IR-120 (H*) resin, filtered and concentrated. The residue is purified by flash chromatography (1.5/1/1 cyclohexane/ ethyl acetate/acetone) in order to obtain 84 in the form of a syrup (22.7 g, 81 % from 82). [α]^ - 58 (c = 1.0, methanol) .
PREPARATION 76
Phenyl 4,6-O-beiizylidene-3-O-methyl-l-seleno-β-D-gluco-
pyrazioside (85) .
P-Toluenesulphonic acid (45 mg) and benzaldehyde dimethyl acetal (5.4 ml, 3 6.0 mmol) are added, under argon, to a solution of triol 84 (7.65 g, 23.0 mmol) in acetonitrile (150 ml). After stirR1ng for 2 hours at room temperature, potassium carbonate (1.5 g) is added. After 30 minutes, the solution is filtered and then concentrated. The residue is purified by flash chromatography (3.5/1 cyclohexane/ethyl acetate) in order to obtain 85 (8.55 g, 88 %) in the form of white crystals. m.p. 123-124°C (cyclohexane/ethyl acetate), [α]D - 38 (c = 1.0, chloroform).
PREPARATION 77
Phenyl 4,6-O-benzylidene-3-O-methyl-2-O-(methyl-
4-deoxy-6-O-dimethylsilyl-2,3-di-O-methyl-4-C-
znethylene-α-D-xylo-hexopyranoside) -l-seleno-|3-D-
glucopyranoside (86).
A 1.6 M solution of n-butyllithium (7.0 ml, 11.2 mmol) is added, under argon and at -70°C, to a solution of 85 (4.30 g, 10.2 mmol) in tetrahydrofuran
(30 ml) placed in a Schlenck tube. After 10 minutes, dichlorodimethylsilane (5.0 ml, 41.2 mmol) is added and the reaction medium is warmed to room temperature. After 3 hours, the mixture is concentrated and a solution of 80 (2.10 g, 9.62 mmol) and imidazole
(985 mg, 14.4 mmol) in tetrahydrofuran (20 ml) is added. After 3 0 minutes at room temperature, the solution is concentrated, water (50 ml) is added and

the mixture is extracted with dichloromethane. The organic phase is dried (magnesium sulphate), filtered and concentrated. An analytical sample of 86 is purified by flash chromatography (2 5/1 toluene/acetone containing 0.5 % triethylamine). A colourless syrup is obtained in a yield of 90 %.
'H NMR (400MHz, C5D6) d 7.77-6.99 (m, lOH, aromatic) , 5.51 (m, IH, C:CH2) , 5.24 (m, IH, C:CH2) , 5.16 (s, IH, CHPh) , 4.85 (d, IH, J = 3.7Hz, H-1), 4.81 (d, IH, J = 9.8Hz, H-1'), 4.45 (m, IH, H-5) , 4.38 (dd, IH, J = 10.8Hz, 4.8Hz, H-6a) , 4.33 (dd, IH, J = 6.2Hz, H-6b) , 4.20 (m, IH, J = 9.2Hz, H-3), 4.05 (dd, IH, J = 10.3Hz, 4.9Hz, H-6a'), 3.87 (dd, IH, J = 8.1Hz, H-2'), 3.52, 3.38, 3.31 and 3.27 (s, 3H, OCH3) , 3.3 7 (t, IH, J = 10.3Hz, H-6b' ) , 3.3 5 (t, IH, H-4' ) , 3.32 (dd, IH, H-2) , 3.22 (dd, IH, J = 9.3Hz, H-3' ) , 3.05 (ddd, IH, J = 9.3Hz, H-5' ) , 0.3 8 and 0.37 (s, 3H, Si (CH3)2. MS (m/z) : 714 (M+NH4).
PREPARATION 78
Radical cycllzation reaction (formation of 87) and
cleavage o£ the tether (88).
A solution of tributyltin hydride (6.1 ml, 22.7 mmol) and 2,2'-azobisisobutyronitrile (200 mg, 1.22 mmol) in degassed toluene (14 ml) is added, over a peR1od of 8 hours, to a solution of crude 86 in toluene (850 ml), obtained from 85 (10.2 mmol) and 80 (9.62 mmol).
After the radical cyclization, the mixture is concentrated and the residue is dissolved in tetrahydrofuran. An excess (20 equivalents) of hydrofluoR1c acid (at a concentration of 40 % in water) is added. After complete desilylation (TLC, 4/1 toluene/acetone), the solution is neutralized by addition of solid sodium hydrogen carbonate, filtered and concentrated. The major compound 88 may be purified by crystallization, m.p. 105°C. [α] D + 119 (c = 1.1, chloroform) . 13C NMR (62.896MH2, CDCl3) d 137.29 (quarternary aromatic C) , 128.88-125.96 (aromatic C) ,

101.11 (CHPh), 9 7.64 (C-1), 83.52 (C-2), 82.76, 81.95, 80.84, 72.01, 71.92 and 64.31 (C-3, C-5, C-2' , C-3' , C-4' , C-5' ) , 75.19 (C-1' ) , 6 9.41 (C-6' ) , 62.69 (C-6) , 60.93, 60.70, 58.31 and 55.20 (OCH3) , 38.80 (C-4), 25.58 (methylene C) .
Anal. Calculated for C24H3O10H2O (502.558) :
C, 57.36/ H, 7.62. Found: C, 57.31; H, 7.54.
PREPARATION 79
Methyl 6-O-acetyl-4-C-(2-O-acetyl-4,6-O-benzylidene-3-O-methyl-α-D-glucopyranosylmethyl)-4-deoxy-2,3-di-O-methyl-α-D-glucopyranoside (89).
Compound 88 is acetylated quantitatively in a mixture of l/l acetic anhydride/pyridine, in the presence of a catalytic amount of 4-dimethylamino-pyridine. The product is obtained after concentration and chromatography, [α]D + 87 (c = 1.0, chloroform) . 'H NMR (500MHz, CDCl3) : see Table 1. 13C NMR (62.896MHz, CDCl3) d 170.81, 16 9.8 0 (C:O) , 137.18 (quartemary aromatic C), 128.92-125.95 (aromatic C), 101.31 (CHPh), 97.51 (C-1), 83.22 (C-2), 81.94, 69,25 and 63.83 (C-5, C-4', C-5'), 81.81 (C-3), 78.78 (C-3'), 72.74 (C-2') , 71.96 (C-1') , 6 9.49 (C-6') , 64.17 (C-6) , 60.64, 59.82, 58.30 and 55.19 (OCH3) , 39.00 (C-4), 26.47 (methylene C) , 20.91, 20.76 (OCOCH3) . Mass spectrum (m/z) : 586 (M+NHJ +, 569 (M+H+554 (M-OMe+NH3) +, 537 (M-OMe)+.
Anal. Calculated for C28H40O12OH20 (586,632) : C, 57.33; H, 7.22. Found: C, 57.28; H, 7.07.
The final part of the synthesis consists in converting 89 into imidate 90. To do this, the benzylidene is opened using sodium cyanoborohydride and hydrochloR1c acid. The hydroxyl group thus freed is temporaR1ly protected in the form of the p-methoxy-benzyl ether. After deacetylation, the pR1mary alcohol function is protected by selective introduction of tert-butyldimethylsilyl ether, and the compound thus obtained is methylated. Oxidation under the Jones conditions leads to the uronic acid, which is

benzylated. The p-methoxybenzyl ether is subsequently cleaved off and a levulinic ester is introduced in this position. A system using a sulphuR1c acid/acetic acid/acetic anhydride mixture leads to acetolysis of the anomeR1c methyl group as well as of the benzyl ether in position 6', and gives a mixture of two anomeR1c acetates. Selective deacetylation of position 1 is carR1ed out using hydrazine in dimethylformamide, and the mixture of anomers, dissolved in dichloro-methane, is converted into 90 with trichloroaceto-nitrile in the presence of 1,8-diazabicyclo[5.4.0]-undec-7-ene.


93
PREPARATION 80
Ethyl O- (2, 3-di-O-benzoyl-4, 6-O-benzylidene-α-D-gluco-pyranosyl) - (l->4) -2, 3, 6-tri-O-benzoyl-l-thio-β-D-glucopyranose (92)
Benzoyl chloride (24.5 ml, 211 mmol) is added dropwise over 20 minutes to a cooled (0°C) solution of compound 91 (16.7 g, 35,2 mmol) (J. Westman and M. Nilsson, J. Carbohydr. Chem., 1995, 14 (7) , 949-960) in pyridine (202 ml) . The reaction mixture is stirred for 2 0 hours at room temperature; TLC reveals an

approximately 5 0% conversion. The mixture is diluted with water and dichloromethane. After extraction, the organic phase is washed with 10% sodium hydrogen carbonate solution, water, dried over magnesium sulphate and concentrated. The residue is again treated with benzoyl chloride according to the procedure descR1bed above. The crude product is purified by chromatography on a column of silica gel to give 22 g of compound 92. TLC: Rf = 0.80, silica gel, 9/1 v/v toluene/ethanol
PREPARATION 81
O-(2,3-Di-O-benzoyl-4,6-O-ben2ylidene-α-D-glucopyranosyl)-(l->4) -O-(2, 3, 6-tri-O-benzoyl-β-D-glucopyranosyl) - (l->4) -1, 6-anhydro-2,3-di-O-methyl-β-D-glucopyranose (94)
A mixture of thioglycoside 92 (1.05 g, 1.05 mmol), compound 93 (200 mg, 1.05 mmol) (Jeanioz et al., J. Org. Chem. 1961, 26, 3939-3944) and powdered 4A molecular sieves (1.1 g) in toluene (18 ml) is stirred under a nitrogen atmosphere for 15 minutes. The mixture is then cooled to -20°C and a freshly prepared solution of N-iodosuccinimide (1.11 mmol) and trifluoromethanesulfonic acid (0.125 mmol) in 1/1 v/v dichloromethane/dioxane (6 ml) is introduced therein. After 10 minutes, the red reaction mixture is filtered, diluted with dichloromethane, extracted, washed successively with 10% sodium thiosulphate solution, 10% sodium hydrogen carbonate solution and water, dried over magnesium sulphate and then concentrated under vacuum. The residue is purified by chromatography, on a column of silica gel in order . to obtain 1.25 g of compound 94.
TLC: Rf = 0.55, silica gel, 4/6 v/v heptane/ethyl acetate

PREPARATION 82
O-(4,6-O-Benzylidene-α-D-glucopyranosyl)-(l->4) -O-(p-D-glucopyranosyl) - (l->4) -1, 6-anhydro-2/ 3-di-O-methyl-β-D-glucopyranose (95)
Potassium tert-butoxide (about 50 mg) is added to a solution of compound 94 (1.24 g, 1.11 mmol) in 1/1 v/v methanol/dioxane (7 ml) . The mixture is stirred for one hour and a further 50 mg of potassium tert-butoxide are then added; the mixture is then stirred for a further 60 minutes. The reaction mixture is neutralized with a Dowex® 50WX8 H* resin, filtered and concentrated under vacuum. After chromatography on a column of silica gel, 665 mg of compound 95 are isolated in the form of an oil.
TLC: Rf = 0.50, silica gel, 85/15 v/v dichloromethane/methanol
PREPARATION 83
O-(4,6-O-Benzylidene-2,3-di-O-methyl-α-D-glucopyranosyl) - (l-»4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (1-^4) -1, 6-anhydro-2,3-di-O-methyl-β-D-glucopyranose (96)
Sodium hydride (387 mg, 9,65 mmol) is added under a nitrogen atmosphere to a cooled (5°C) solution of compound 95 (660 mg, 1.1 mmol) in dry tetrahydrofuran (8 ml). Methyl iodide (0.51 ml, 8.22 mmol) is added dropwise and the mixture is stirred for 20 hours at room temperature. The excess sodium hydride is destroyed with methanol and the mixture is poured into 50 ml of ice-cold water. After extraction with ethyl acetate (3 times 20 ml) , the organic phase is washed with sodium chloride solution, dried over magnesium sulphate and concentrated to give 690 mg of pure compound 96.
TLC: Rf = 0.25, silica gel, 95/5 v/v dichloromethane/methanol

PREPARATION 84
O-(2,3-Di-O-methyl-α-D-glucopyranosyl)-(l-»4) -O-2,3, 6-tri-O-methyl-β-D-glucopyranosyl)- (l->4) -1,6-anhydro-2,3-di-O-lnethyl-β-D-glucopyranose (97)
The pure compound 96 (690 mg, 1.03 mmol) is dissolved in 80% acetic acid (7.3 ml) and stirred for 20 hours at 40oC. The mixture is concentrated under vacuum and co-evaporated with toluene. Chromatography on a column of silica gel in 8/1/1 dichloromethane/ethyl acetate/methanol allows 56 9 mg of compound 97 to be obtained.
TLC: Rf = 0.40, silica gel, 9/1 v/v dichlorome thane/methanol
PREPARATION 85
O-(6-O-Benzoyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(1-^4)-O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl)-(1^-4) -1,6-anhydro-2,3-di-O-methyl-β-D-glucopyranose (98)
1-Benzoyloxy-lH-benzotriazole (227 mg, 1.05 mmol) and triethylamine (1.15 mmol) are added to a solution of compound 97 (560 mg, 0.96 mmol) in dichlorome thane and the mixture is then stirred for 20 hours at room temperature. The reaction mixture is diluted with dichoromethane and washed with 10% sodium hydrogen carbonate solution and water. The organic phase is dried over magnesium sulphate, filtered and evaporated to dryness. The product is purified by chromatography on a column of silica gel in order to obtain 600 mg of compound 98-
TLC: Rf = 0.50, silica gel, 9/1 v/v dichloro-methane/methanol
PREPARATION 86
O-(2,3-Di-O-benzoyl-4,S-O-benzylidene-α-D-glucopyranosyl)-(1-^4) -O-(2, 3, 6-tri-O-benzoyl-β-D-glucopyranosyl) - (l->4) -O- (6-O-benzoyl-2, 3-di-O-methyl-α-D-glucopyranosyl)- (l->4) -O-(2, 3, S-tri-O-methyl-β-D-glucopyranosyl) - (1-^4) -1, 6-anhydro-2, 3-di-O-methyl-β-D-glucopyranose (99)

Compound 98 is converted into compound 99 according to the procedure descR1bed for the preparation of compound 94. The coupling reaction is carried out at 5°C.
TLC: Rf - 0.50, silica gel, 2/8 v/v heptane/ethyl acetate



PREPARATION 87
O-(4,6-O-Benzylidene-α-D-glucopyranosyl)-(1->4) -O- (P-D-glucopyranosyl) - (l->4) -O- (2, 3-di-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2,3,6-tri-O-niethyl-β-D-glucopyranosyl) - (l->4) -1, 6-aiihydro-2, 3-di-O-methyl-β-D-glucopyranose (100)
Compound 9 9 is converted into compound 10 0 according to the same procedure as that descR1bed for the preparation of compound 95.
TLC: Rf = 0.35, silica gel, 9/1 v/v dichloro-methane/methanol
PREPARATION 88
O- (4, 6-O-Benzylidene-2, 3-di-O-niethyl-α-D-glucopyranosyl) - (1-^4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (l->4) -O- (2,3, 6-tri-O-methyl-α-D-glucopyranosyl) - (l->'4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (l->4) -1, 6-anhydro-2, 3-di-O-methyl-β-D-glucopyranose (101)
Compound 100 is converted into compound 101 according to the same procedure as that descR1bed for the preparation of compound 96,
TLC: Rf = 0.50, silica gel, 9/1 v/v dicholoro-me thane/met hand
PREPARATION 89
O- (2,3-Di-O-methyl-α-D-glucopyranosyl) - (1^4) -O- (2,3,6-tri-O-methyl-β-D-glucopyranosyl)-(l->4) -O-(2,3,6-tri-O-methyl-α-D-glucopyranosyl) - (l-»4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (l->4) -1, 6-anhydro-2, 3-di-O-methyl-β-D-glucopyranose (102)
Compound 101 is converted into compound 102 according to the same procedure as that descR1bed for the preparation of compound 97.
TLC: Rf = 0.35, silica gel, 9/1 v/v dichloro-methane/methanol

PREPARATION 90
O-(6-O-Benzoyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(l->4)-O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl)-(1^4) -O-(2,3,6-tri-O-methyl-α-D-glucopyranosyl)- (1-^4) -O-(2,3,S-tri-O-methyl-β-D-glucopyranosyl)-(1-^4) -1,6-anhydro-2,3-di-O-methyl-β-D-glucopyranose (103)
Compound 102 is converted into compound 103 according to the same procedure as that descR1bed for the preparation of compound 98.
TLC: Rf = 0.40, silica gel, 7.0/1.5/1.5 v/v/v toluene/ethyl acetate/ethanol
PREPARATION 91
O-(2,3-Di-O-benzoyl-4,6-O-benzylidene-α-D-glucopyranosyl)- (l->4) -O-(2,3, 6-tri-O-benzoyl-β-D-glucopyranosyl) - (l->4) -O- (6-O-benzoyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(1^-4) -O-(2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (l->'4) -O- (2,3, 6-tri-O-methyl-α-D-glucopyranosyl)- (l->4) -O-(2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (l->4) -1, 6-aiihydro-2, 3-di-O-methyl-(3-D-glucopyraziose (104)
The coupling reaction of compound 103 with the disaccharide 2 is carried out according to the procedure descR1bed for the preparation of compound 99, TLC: Rf = 0.40, silica gel, 7.0/1.5/1.5 v/v/v toluene/ethyl acetate/ethanol



PREPARATION 92
O-(4,6-O-Benzylidene-α-D-glucopyranosyl)-(l->4) -O- (P-D-glucopyranosyl) - (1->4) -O- (2 , 3-di-O-methyl-α-D-glucopyranosyl)- (1^4) -O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl) - (1^4) -O- (2,3, S-tri-O-methyl-α-D-glucopyranosyl) - (1-^4) -O- (2,3, 6-tri-O-methyl-(3-D-glucopyranosyl) - (l->4) -1, 6-anhydro-2, 3-di-O-methyl-β-D-glucopyranose (105)
Compound 104 is converted into compound 105 according to the same procedure as that descR1bed for the preparation of compound 95.
TLC: Rf = 0.60, silica gel, 9/1 v/v dichloro-methane/methanol
PREPARATION 93
O-(4,6-O-Benzylidene-2,3-di-O-methyl-α-D-glucopyranosyl)- (l->4) -O-(2,3, 6-tri-O-methyl-β-D-glucopyranosyl)-(l->4) - [O-(2,3, 6-tri-O-methyl-α-D-glucopyranosyl)- (1-^4) -O-(2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (1^4) ] 2-l, 6-anhydro-2,3-di-O-methyl-β-D-glucopyranose (106)
Compound 105 is converted into compound 106 according to the same procedure as that descR1bed for the preparation of compound 96.
TLC: Rf = 0.70, silica gel, 9/1 v/v dichloro-methane/methanol
PREPARATION 94
O- (2,3-Di-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2,3,6-tri-O-methyl-β-D-glucopyranosyl) - (l->4) - [O- (2,3, 6-tri-O-methyl-α-D-glucopyratnosyl) - (l->4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyrauiosyl) - (l->4) ] j-l/ 6-anhydro-2/ 3-di-O-methyl-β-D-glucopyranose (107)
A solution of compound 106 (5.05 g, 2.0 mmol) in 8 0% acetic acid (50 ml) is stirred for 2 0 hours at 40°C. The mixture is concentrated under vacuum and co-evaporated with toluene. The residue is dissolved in ethyl acetate and extracted with water The aqueous phase is extracted with dichloromethane and the organic

phase is dried over magnesium sulphate, tiltered and evaporated to dryness to give 2.68 g of compound 107. TLC: Rf = 0.50, silica gel, 9/1 v/v dichloro-methane/methanol
PREPARATION 95
O-(6-O-Benzoyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(l->4)-O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl)-(1-^4) -[O-(2,3,S-tri-O-methyl-α-D-glucopyranosyl)- (l->4) -O-(2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (1-^4) ] ^-l/ 6-aiihydro-2,3-di-O-methyl-β-D-glucopyranose (108)
Compound 107 is converted into compound 108 according to the same procedure as that descR1bed for the preparation of compound 98.
TLC: Rf = 0,80, silica gel, 7.0/1.5/1.5 v/v/v toluene/ethyl acetate/ethanol
PREPARATION 96
O- (2, 3-Di-O-benzoyl-4, S-G-benzylidene-α-D-glucopyranosyl) - (l->4) -O- (2, 3, 6-tri-O-benzoyl-β-D-glucopyranosyl)-(1,4)-O-(6-O-benzoyl-2,3-di-O-methyl-α-D-glucopyrauiosyl) - (1^4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyranosyl)-(l->4) - [O-(2, 3, 6-tri-O-methyl-α-D-glucopyranosyl) - (1^4) -O- (2,3, 6-tri-O-methyl-(3-D-glucopyranosyl) - (l->4) ] ]2-l, 6-aiihydro-2, 3-di-O-methyl-β-D-glucopyranose (109)
A mixture of the thioglycoside 92 (1.97 g, 2.0 mmol, 3.5 eq), heptasaccharide 108 (0.86 g, 0.57 mmol) and powdered 4A molecular sieves in toluene (22 ml) is stirred under a nitrogen atmosphere for 15 minutes. A freshly prepared solution containing N-iodosuccinimide (496 mg, 2.2 mmol) and trifluoro-methanesulphonic acid (0.808 mmol) in 1/1 v/v dichloro-methane/dioxane (12 ml) is then added dropwise at room temperature. After 10 minutes, the reaction mixture is filtered, diluted with dichloromethane, extracted, washed with 10% sodium thiosulphate solution and with 10% sodium hydrogen carbonate solution, dried over magnesium sulphate and concentrated under vacuum. The

crude product is purified by chromatography on a column of silica gel, to give 1.09 g of compound 109. TLC: Rf = 0.80, silica gel, 6/2/2 v/v/v toluene/ethyl acetate/ethanol



PREPARATION 97
O-(4,6-O-Benzylidene-α-D-glucopyranosyl)-(1^4) -O-(P-D-glucopyranosyl)- (1^4) -O-(2,3,-di-O-methyl-α-D-glucopyranosyl)- (l->4) -O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl)-[(1-4)-O-(2,3,6-tri-O-methyl-α-D-glucopyranosyl)- (1^4) -O-(2,3,S-tri-O-methyl-β-D-glucopyranosyl) ] j- (l->4) -1, 6-anhydro-2, 3-di-O-methyl-β-D-glucopyranose (110)
Compound 109 is converted into compound 110 according to the same procedure as that descR1bed for the preparation of compound 95.
TLC: Rf = 0.25, silica gel, 5,0/2.5/2.5 v/v/v toluene/ethyl acetate/ethanol
PREPARATION 98
O- (4, 6-O-Beii2ylidene-2, 3-di-O-methyl-α-D-glucopyranosyl)- (l->4) -O-(2,3, S-tri-O-methyl-β-D-glucopyranosyl)-(l->4) - [O-(2, 3, 6-tri-O-methyl-α-D-glucopyranosyl)-(l->4) -O-(2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (l->4) ] 3-I, 6-anhydro-2, 3-di-O-methyl-β-D-glucopyranose (111)
Compound 110 is converted into compound 111 according to the same procedure as that descR1bed for the preparation of compound 96,
TLC: Rf = 0.50, silica gel, 6/2/2 v/v/v toluene/ethyl acetate/ethanol
PREPARATION 99
O- (2,3-Di-O-methyl-α-D-glucopyranosyl) - (1^4) -O- (2,3,6-tri-O-methyl-β-D-glucopyranosyl)- (1-^4) -[O-(2,3,6-tri-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (l->4) ] 3-I, 6-aiihydro-2, 3-di-O-methyl-β-D-glucopyranose (112)
Compound 111 is converted into compound 112 according to the same procedure as that descR1bed for the preparation of compound 97.
TLC: Rf = 0.20, silica gel, 6/2/2 v/v/v toluene/ethyl acetate/ethanol

PREPARATION 100
O-(6-O-Benzoyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(l->4)-O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl)-(l->4) -[O-(2,3,6-tri-O-methyl-α-D-glucopyranosyl)-(l->4) -O-(2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (l->4) ] 3-I, 5-
anhydro-2,3-di-O-methyl-β-D-glucopyranose (113)
Compound 112 is converted into compound 113
according to the same procedure as that descR1bed for
the preparation of compound 98.
TLC: Rf = 0.20, silica gel, 6/2/2 v/v/v toluene/ethyl
acetate/ethanol
PREPARATION 101
O-(6-O-Benzoyl-4-O-levulinyl-2,3-di-O-methyl-α-D-glucopyranosyl) - (l->'4) -O- (2,3, 6-tri-O-methyl-(3-D-glucopyranosyl) - (l->4) - [O- (2,3, 6-tri-O-methyl-α-D-glucopyranosyl) - (l->'4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (l->'4) ] 3-I, 6-aiihydro-2, 3-di-O-methyl-β-D-glucopyranose (114)
1-{3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (48 mg, 0.25 mmol), levulinic acid (29 mg, 0.25 mmol) and dimethylaminopyridine (4 mg, 0.033 mmol) are added to a solution of compound 113 (320 mg, 0.167 mmol) in dioxane (1 ml). The reaction mixture is stirred for 3 hours at room temperature under a nitrogen atmosphere. Dichloromethane and water are then added and, after extraction, the organic phase is washed with water, dried over magnesium sulphate, filtered and concentrated. The crude product is purified by chromatography on a column of silica gel to give 312 mg of compound 114.
TLC: Rf = 0.50, silica gel, 6/2/2 v/v/v toluene/ethyl acetate/ethanol
PREPARATION 102
O- (6-O-Benzoyl-4-O-leviilinyl-2, 3-di-O-methyl-α-D-glucopyranosyl)- (1-^4) -O-(2,3, 6-tri-O-methyl-β-D-glucopyranosyl)-(1^4) - [O-(2,3, 6-tri-O-methyl-α-D-glucopyranosyl) - (1">^4) -O- (2,3, S-tri-O-methyl-β-D-

glucopyranosyl) - (l->4) ] 3-I, 6-di-O-acetyI-2 , 3-di-O-methyl-a,p-D-glucopyranose (115)
A solution of compound 114 (312 mg, 0.155 mmol) in a mixture of acetic anhydride (2.25 ml), acetic acid (50 μl) and trif luoroacetic acid (0.14 ml) is stirred for 4 hours at room temperature. After addition of toluene (10 ml), the mixture is concentrated and co-evaporated with toluene (3 times 10 ml). After chromatography on a column of silica gel, 324 mg of compound 115 are isolated.
TLC: Rf = 0,65, silica gel, 6/2/2 v/v/v toluene/ethyl acetate/ethanol

SCHEME 27 - Synthesis of the oligosaccharide 117

A solution of compound 115 (324 mg, 0.153 mmol) and morpholine (22.3 μ1, 0.256 mmol) in toluene (2 ml) is stirred for 4 hours at 35oC. Morpholine (22.3 μ1) is then added again and the reaction mixture is stirred for 2 0 hours at 3 5 ° C. The mixture is cooled rapidly with water. After extraction with dichloromethane, the organic phase is washed successively with 0.IN hydrochloR1c acid and water, dried and evaporated to dryness. After chromatography on a column of silica gel, 280 mg of compound 116 are isolated. TLC: Rf = 0.45, silica gel, 6/2/2 v/v/v toluene/ethyl acetate/ethanol
PREPARATION 104
O-(6-O-Benzoyl-4-O-levulinyl-2,3-di-O-methyl-α-D-glucopyranosyl)-(l->4) -O-(2,3, S-tri-O-methyl-β-D-glucopyranosyl)-(l->4) - [O-(2,3, 6-tri-O-methyl-α-D-glucopyranosyl)-(1-^4) -O-(2,3,6-tri-O-methyl-β-D-

glucopyranosyl) - (1-^4) ] 3-6-O-acetyl-2, 3-di-O-methyl-a, P-D-glucopyranose trichloroacetimidate(117)
trichloroacetonitrile (39μ1, 0.39 mmol) and caesium carbonate (4.7 mg) are added to a solution of compound 116 (138 mg, 0.066 mmol) in dichloromethane (1.5 ml). After stirR1ng for 2 hours, the mixture is filtered and concentrated and the residue is chromatographed on a column of silica gel to give 152 mg of the imidate 117.
TLC: Rf = 0.35, silica gel, 8/1/1 v/v/v toluene/ethyl acetate/ethanol



PREPARATION 105
Methyl 2-O-benzyl-4,6-O-benzylidene-α-D-glucopyranoside (119)
The compound 118 (60 g) (commercially available) is dissolved in dimethylformamide (858 ml) with benzyl bromide (50.5 ml). After cooling to 10°C, aqueous 20% sodium hydroxide solution is added dropwise. After stirR1ng for 1 hour, the temperature is raised to 20°C and the mixture is stirred for a further 20 hours. The solution is then poured into a mixture of ice-water and toluene and extracted. The organic phase is concentrated and the crude product is purified by crystallization to give 30.0 g of compound 119. TLC: Rf = 0.60, silica gel, 7/3 v/v toluene/ethyl acetate
PREPARATION 106
Methyl 2-O-benzyl-4,6-O-benzylidene-3-O-β-methoxy-
benzyl-α-D-glucopyranoside (120)
Compound 119 (26.4 g) is dissolved in dimethylf ormamide (211 ml) and cooled to 5®C. Sodium hydride (2.5 g) is added under a nitrogen atmosphere. 4-methoxybenzyle chloride (13.3 g) is then added dropwise and the mixture is stirred for 1 hour at room temperature. The mixture is diluted with ethyl acetate, washed twice with water and concentrated to give 4 0.7 g of pure compound 120.
TLC: Rf = 0.80, silica gel, 7/3 v/v toluene/ethyl acetate
PREPARATION 107
Methyl 2-O-benzyl-3-O-β-inethoxybenzyl-α-D-gluco-
pyranoside (121)
Compound 120 (34.9 g) is dissolved in aqueous 60% acetic acid and stirred for 4 hours at 60oC. The mixture is diluted with toluene and concentrated. Purification by chromatography on a column of silica gel allows 26.4 g of compound 121 to be obtained.

TLC: Rf = 0.07, silica gel, 7/3 v/v toluene/ethyl acetate
PREPARATION 108
Methyl 2-O-benzyl-3-O-β-methoxybenzyl-6-O-methyl-α-D-
glucopyranoside (122)
Compound 121 (26.4 g) is dissolved in dichloromethane (263 ml) under a nitrogen atmosphere. trimethyloxonium tetrafluoroborate (11.6 g) and 2,6-di-tert-butyl-4-methylpyridine (17.4 g) are added at room temperature. After 4 hours, the mixture is poured onto ice-water and extracted with dichloromethane. The organic phase is washed with sodium hydrogen carbonate and concentrated. Purification of the crude product by chromatography on a column of silica gel allows 18.5 g of compound 122 to be obtained.
TLC: Rf = 0.25, silica gel, 7/3 v/v toluene/ethyl acetate
PREPARATION 109
Ethyl 2,4,6-tri-O-acetyl-3-O-methyl-l-thio-α-L-
idopyranose (124)
Compound 123 (1,2,4,6-tetrα-O-acetyl-3-O-methyl-α-L-idopyranose) (Jaurand et al. Bio. Med. Chem. Lett. 19 92, 2, 8 97-900) (48.4 g) is dissolved in toluene (175 ml). Ethanethiol (20 ml) and boron trifluoride etherate in toluene (134 ml) are added, under a nitrogen atmosphere. After stirR1ng for 1 hour, aqueous sodium hydrogen carbonate (400 ml) is added and the mixture is stirred for a further one hour. The mixture is then poured into ethyl acetate. The organic phase is washed twice with water and concentrated. Purification by chromatography on a column of silica gel allows 2 9.6 g of compound 124 to be obtained. TLC: Rf = 0.45, silica gel, 6/4 v/v toluene/ethyl acetate

PREPARATION 110
Methyl O-(2,4,6-tri-O-acetyl-3-O-methyl-α-L-
idopyranosyl- (l->4) -2-O-benzyl-3-O-β-inethoxybenzyl-6-O-methyl-α-D-glucopyranoside (125)
Compound 122 (17.5 g) and compound 124 (28.2 g) are dissolved in toluene (525 ml) under a nitrogen atmosphere. After adding 4A molecular sieves, the reaction is cooled to -20®C. A freshly prepared solution of 0. IM N-iodosuccinimide (17.4 g) and trifluoromethanesulphonic acid (1.38 ml) in 1/1 v/v dioxane/dichloromethane is added dropwise under a continuous flow of nitrogen. After 10 minutes, the red reaction mixture is filtered and washed successively with aqueous sodium thiosulphate and aqueous sodium hydrogen carbonate. The organic phase is concentrated under vacuum and 30.0 g of compound 125 are isolated. TLC: Rf = 0.45, silica gel, 8/2 v/v dichloro-methane/ethyl acetate
PREPARATION 111
Methyl O- O-O-methyl-α-L-idopyranosyl) - (l->'4) -2-O-
benzyl-3-O-β-methoxybenzyl-6-O-methyl-α-D-
glucopyranoside (126)
Compound 125 (30.0 g) is dissolved in 460 ml of 1/1 v/v methanol/dioxane and potassium tert-butoxide is added. After 15 minutes, the mixture is neutralized with a Dowex 50WX8H+ resin and concentrated under vacuum. Purification is carried out by chromatography on a column of silica gel to give 17.4 g of compound 126.
TLC: Rf = 0.25, silica gel, 95/5 v/v dichloro-methane/methanol
PREPARATION 112
Methyl O-(4,6-O-isopropylidene-3-O-methyl-α-L-
idopyranosyl) - (l->4) -2-O-benzyl-3-O-β-inethoxybenzyl-6-O-methyl-α-D-glucopyranoside (127)
Compound 126 (17.4 g) is dissolved in dimethylformamide (77 ml) under a nitrogen atmosphere.

2,2-Dimethoxypropane {26 ml) and p-toluenesulphonic acid are added and the mixture is then stirred for 3 0 minutes. Dilution of the mixture with aqueous sodium hydrogen carbonate followed by its extraction with ethyl acetate allows 19.7 g of compound 127 to be obtained after evaporation of the solvent. TLC: Rf = 0.45, silica gel, 95/5 v/v dichloromethane/methanol
PREPARATION 113
Methyl O- (4/ 6-O-isopropylidene-2, 3-di-O-methyl-α-L-idopyranosyl) - (l->4) -2-O-benzyl-3-O-inethoxybenzyl-6-O-methyl-α-D-glucopyranoside (128)
Compound 127 (18.5 g) is dissolved in dimethylformamide (24.4 ml) and cooled to 0°C. Sodium hydride (1.47 g; 60% dispersion in oil) and iodomethane (2.36 ml) are added under a nitrogen atmosphere. After one hour, the excess sodium hydride is destroyed with methanol and the mixture is extracted with dichloromethane and concentrated to give 20.0 g of compound 128.
TLC: Rf = 0.85, silica gel, 95/5 v/v dichloro-methane/methanol



PREPARATION 114
Methyl O-(4,6-O-isopropylidene-2,3-di-O-methyl-α-L-ido-pyranosyl) - (l->4) -2-O-benzyl-6-O-methyl-α-D-glucopyranoside (12 9)
Compound 128 (18.4 g) is dissolved in dichloromethane (838 ml) and water (168 ml) . 2,3-Dichloro-5,6-dicyano-l,4-benzoquinone (7.1 g) is added and the mixture is stirred for 18 hours at A^C. The mixture is poured into aqueous sodium hydrogen carbonate and extracted with dichloromethane. Concentration of the organic phase gives 12.7 g of compound 129.
TLC: Rf = 0.40, silica gel, 95/5 v/v dichloromethane/methanol
PREPARATION 115
Methyl O-(4,6-O-isopropylidene-2,3-di-O-methyl-α-L-ido-pyranosyl) - (l->4) -2,3-di-O-benzyl-6-O-methyl-α-D-glucopyranoside (130)
Compound 129 (10.5 g) is dissolved in dry dimethylformamide (178 ml) and then cooled to 0°C under a nitrogen atmosphere. Sodium hydride (1.91 g; 60% dispersion in oil) is added, followed by dropwise addition of benzyl bromide (3.3 ml). After 30 minutes, the reaction is complete and the excess sodium hydride is destroyed with methanol. Water is added and the mixture is extracted twice with ethyl acetate. Evaporation of the solvent allows 13.6 g of compound 130 to be obtained.
TLC: Rf = 0.50, silica gel, 1/1 v/v toluene/ethyl acetate
PREPARATION 116
Methyl O-(2,3-di-O-methyl-α-L-idopyranosyl)-(l->4) -2,3-
di-O-benzyl-S-O-methyl-α-D-glucopyranoside (131)
Compound 130 is dissolved in 77/33 (v/v) acetic acid/water and stirred overnight. The mixture is co-evaporated twice with toluene and purified by

chromatography on a column of silica gel to obram
11.5 g of compound 131.
TLC: Rf = 0.09, silica gel, 1/1 v/v toluene/ethyl
acetate
Rf = 0.68, silica gel, 9/1 v/v
dichloromethane/methanol
PREPARATION 117
Methyl O-(2,3-di-O-methYl-α-L-idopyranosyluronic acid)-
(1^'4)-2,3-di-O-benzyl-6-O-methyl-α-D-glucopyranoside
(132)
Free radical 2,2,6,6-tetramethyl-l-piperidinyloxy(33 mg) , sodium hydrogen carbonate solution (40 ml) , potassium bromide (218 mg) and tetrabutylammonium chloride (289 mg) are added to a solution of compound 131 (11.6 g) in dichloromethane (60 ml) • The mixture is cooled to 0oC and a mixture of saturated sodium chloride solution (44 ml), saturated sodium hydrogen carbonate solution (21.8 ml) and sodium hypochloR1te (1.3 M, 50 ml) is added over 15 minutes. After stirR1ng for 1 hour, the mixture is diluted with water and extracted (3 times) with dichloromethane. The organic phase is washed with aqueous sodium chloride solution, dried over magnesium sulphate, filtered and evaporated to dryness to give 13.4 g of the crude compound 132,
TLC: Rf = 0.14, silica gel, 9/1 v/v dichloromethane/methanol
PREPARATION 118
Methyl O-(benzyl 2,3-di-O-methyl-α-L-idopyrano-syluronate) - (l->4) -2 ,3-di-O-benzyl-6-O-methyl-α-D-glucopyranoside (133)
Compound 132 is dissolved in dimethylformamide (110 ml) under a nitrogen atmosphere. Potassium :iydrogen carbonate (5.7 g) and benzyl bromide (10.7 ml) are added and the mixture is stirred for 90 minutes. i:thyl acetate and water are added and, after extraction, the organic phase is concentrated.

Purification by chromatography on a column oz silica
gel allows 9.9 g of compound 133 to be obtained.
TLC: Rf = 0.43, silica gel, 4/6 v/v toluene/ethyl
acetate
PREPARATION 119
Methyl O-(benzyl 2,3-di-O-methyl-β-D-
glucopyranosyluronate)- (l->4) -2, 3-di-O-benzyl-6-O-methyl-α-D-glucopyranoside (134)
Compound 133 (9.9 g) is dissolved in 300 ml of methanol and heated to reflux under a nitrogen atmosphere. A IM solution of sodium methoxide in methanol (65.2 ml) is added dropwise and the mixture is stirred and heated at reflux for 3 hours. The mixture is then cooled to room temperature, IN sodium hydroxide (22.2 ml) is added and the reaction mixture is stirred for a further 90 minutes. After neutralization with Dowex 50WX8H* resin and filtration, the mixture is concentrated. The pure product is dissolved in dimethylformamide (192 ml) and molecular sieves are added under a nitrogen atmosphere. Potassium hydrogen carbonate (3.2 g) and benzyl bromide (4.8 ml) are added and the mixture is stirred for 5 hours. After addition of ethyl acetate and water, extraction and separation of the two phases, the organic phase is concentrated. The crude product is purified by chromatography on a column of silica gel to give 6.19 g of compound 134 and 1.88 g of the starting compound 133.
TLC: Rf = 0.55, silica gel, 4/6 v/v toluene/ethyl acetate
PREPARATION 120
Methyl O-(benzyl 4-O-levulinyl-2, 3-di-O-methyl-β-D-glucopyranosyluronate) - (1^4) -2,3-di-O-benzyl-6-O-methyl-α-D-glucopyranoside (135)
Compound 134 (6,2 g) is dissolved in 40 ml of
dioxane. Levulinic acid (2.1 g) , dicyclo-
hexylcarbodiimide (3.75 g) and 4-dimethylaminopyridine
(0.2 g) are added and the mixture is stirred for

2 hours under a nitrogen atmosphere. Diethyl ether (95 ml) is added and the precipitate is filtered off. The filtrate is washed with aqueous potassium hydrogen sulphate, dried over magnesium sulphate, filtered and concentrated. Crystallization from ether/heptane allows 6.2 g of compound 135 to be obtained.
TLC: Rf = 0.26, silica gel, 95/5 v/v dichloromethane/acetone
PREPARATION 121
O-(Benzyl 4-O-levulinyl-2,3-di-O-methyl-β-D-gluco-pyranosyluronate) - (l->4) -1, 3-di-O-acetyl-2-O-benzyl-6-O-methyl-a,p-D-glucopyranos8 (136)
Compound 135 (6.1 g) is dissolved in acetic anhydride (256 ml) under a nitrogen atmosphere and cooled to -20°C. A mixture of sulphuR1c acid (4.9 ml) in acetic anhydride (4 9 ml) is added dropwise over 3 0 minutes. After 60 minutes, sodium acetate is added until a mixture having a neutral pH is obtained. Ethyl acetate and water are then added and the organic phase is concentrated. Purification by chromatography on a column of silica gel allows 4.2 g of compound 136 to be obtained.
TLC: Rf = 0.24, silica gel, 8/2 v/v dichloromethane/ethyl acetate
PREPARATION 122
O-(Benzyl 4-O-levulinyl-2,3-di-O-methyl-β-D-gluco-pyranosyluronate) - (l->'4) -3-O-acetyl-2-O-benzyl-6-O-methyl-a,p-D-glucopyranose (137)
Compound 136 (4.2 g) is dissolved in tetrahydrofuran (42 ml) and piperidine (4.1 ml) is added. The mixture is stirred overnight at room temperature. Ethyl acetate is added and the mixture is washed with 0.5 N hydrochloR1c acid. The organic phase is concentrated and the residue is purified by chromatography on a column of silica gel to give 3.2 g of compound 137.

TLC; Rf = 0.33, silica gel, 1/1 v/v
dichloromethane/ethyl acetate
PREPARATION 123
O- (Benzyl 4-O-levulinyl-2 , 3-di-O-methyl-α-D-
glucopyranosyluronate) - (l->4) -3-O-acetyl-2-O-beiizyl-6-O-methyl-α-D-glucopyranose trichloroacetimidate (13 8)
Compound 137 (1.59 g) is dissolved in dry dichloromethane under a nitrogen atmosphere. trichloroacetonitrile (1.1 ml) and caesium carbonate (72 mg) are added and the mixture is stirred for 1 hour. The caesium carbonate is filtered off and the filtrate is concentrated- Purification by chromatography on a column of silica gel allows 1.57 g of compound 13 8 to be obtained.
TLC: Rf = 0.60, silica gel, 3/7 v/v toluene/ethyl acetate

PREPARATION 124
Methyl O- (benzyl 4-O-levulinyl-2,3-di-O-methyl-β-D-
glucopyranosyluronate) - (1→4) -O- (3-O-acetyl-2-0-benzyl-

6-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (benzyl 2,3-di-O-methyl-α-L-idopyranosyluronate)-(l->4) -2 , 3-di-O-benzyl-6-O-methyl-α-D-glucopyranoside (13 9)
A mixture of compound 133 (300 mg) and compound 138 (455.6 mg) is co-evaporated with toluene and dissolved in dichloromethane (6 ml) under a nitrogen atmosphere, After addition of 4A molecular sieves, the mixture is cooled to -20'='0. After stirR1ng for 2 0 minutes, trimethylsilyl trifluoromethanesulphonate (15 mol% relative to compound 138) is added. After 10 minutes, the mixture is quenched with aqueous sodium hydrogen carbonate. After filtration of the molecular sieves, the filtrate is diluted with dichloromethane, washed with water, concentrated and purified by chromatography on a column of silica gel to give 560 mg of compound 13 9,
TLC: Rf = 0.50, silica gel, 3/7 v/v toluene/ethyl acetate
PREPARATION 125
Methyl O-(benzyl 2,3-di-O-methyl-β-D-
glucopyranosyluronate) - (1^-4) -O- (3-O-acetyl-2-O-benzyl-6-O-methyl-α-D-glucopyranosyl) - (1—►4) -O- (benzyl 2, 3-di-O-methyl-α-L-idopyranosyluronate) - (l->4) -2,3-di-O-benzyl-6-O-methyl-α-D-glucopyrsaxoside (140)
Compound 139 (532.6 mg) is dissolved in pyridine (1.9 ml) and a mixture of acetic acid (2.4 ml) and hydrazine hydrate (0.3 ml) in pyridine (1.9 ml) is added at room temperature. After stirR1ng for 9 minutes, dichloromethane and water are added. The organic phase is separated out and washed successively with 0.1 N hydrochloR1c acid, aqueous sodium hydrogen carbonate and water. The organic phase is concentrated and purified by chromatography on a column of silica gel to give 451 mg of compound 140.
TLC: Rf = 0.45, silica gel, 3/7 v/v toluene/ethyl acetate



PREPARATION 12 6
Methyl O-(6-O-benzoyl-4-O-levulinyl-2,3-di-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyranosyl)- (l->4) - [O-(2,3, 6-tri-O-methyl-α-D-glucopyranosyl)- (1^4) -O-(2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (l->4) ] 3-O- (6-O-acetyl-2, 3-di-O-methyl-α-D-glucopyranosyl) - (l->'4) -O- (benzyl 2, 3-di-O-methyl-β-D-glucopyranosyluronate)- (1->4) -O-(3-O-acetyl-2-O-benzyl-6-O-methyl-α-D-glucopyranosyl) - (1-^4) -O- (benzyl 2, 3-di-O-methyl-α-L-idopyranosyluronate) - (l->4) -2, 3-di-O-benzyl-6-O-methyl-α-D-glucopyranoside (141)
A mixture of compound 117 (144 mg, 0.064 mmol) and compound 140 (76 g, 0,058 mmol) is co-evaporated with toluene and dissolved in 1/2 v/v dichloromethane/diethyl ether (3.0 ml). 4A molecular sieves (140 mg) are added under a nitrogen atmosphere and the mixture is cooled to 0°C. Tert-butyldimethylsilyl trifluoromethanesulphonate (128 |il of a 0.1 molar solution in dichloromethane) is added and, after 15 minutes, the mixture is quenched with sodium hydrogen carbonate solution. After extraction with water and dichloromethane, the organic phase is dried and concentrated. The product is first purified by chromatography on Sephadex LH 20 (1/1 v/v lichloromethane/methanol) and then by chromatography on a column of silica gel, to give 124 mg of compound 141 in an a/p ratio of 8/2. TLC: Rf = 0.60, silica gel, 1/1 v/v toluene/acetone
PREPARATION 127
4ethyl O- (6-O-benzoyl-2, 3-di-O-methyl-α-D-
glucopyranosyl) - (1-^4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (l->4) - [O- (2,3, 6-tri-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2, 3, S-tri-O-methyl-β-D-glucopyranosyl) - (1^4) ] 3-O- (6-O-acetyl-2, 3-di-O-methyl-x-D-glucopyranosyl)-(l->4) -O- (benzyl 2,3-di-O-methyl-β-p-glucopyranosyluronate) - (l->4) -O- (3-O-acetyl-2-O-benzyl-6-O-methyl-α-D-glucopyranosyl) - (1-^4) -O- (benzyl

2 , 3 -di-O-methyl-α-L-idopyranosyluronate) - (l->4) -2 , 3-di-O-benzyl-S-O-methyl-α-D-glucopyranoside (142)
Compound 141 is converted into compound 142 according to the procedure descR1bed for the preparation of compound 140.
Compound 142 is isolated as an 8/2 a/p mixture. TLC: Rf = 0.45, silica gel, 1/1 v/v toluene/acetone



PREPARATION 12 8
O- (2,3,4,6-Tetra-O-acetyl-α-D-glucopyranosyl)-(1^4) -O-(2,3,6-tri-O-acetyl-α-D-glucopyranosyl)-(1→4) -1,2,3,6-tetrα-O-acetyl-β-D-glucopyranose (144)
Maltotriose (7 g, 13.9 mmol) (commercially available) is added portionwise to a suspension of sodium acetate (7 g, 8 5 mmol) in acetic anhydride (70 ml) at 155'=*C. After 15 minutes, the clear solution is cooled and quenched with ice-water (700 ml) . After extraction with ethyl acetate, the organic phase is washed with water, dried over magnesium sulphate, filtered and concentrated to give 13.1 g of compound 144.
TLC: Rf = 0.53, silica gel, 7/3 v/v dichloromethane/ethyl acetate
PREPARATION 129
Ethyl O-(2,3,4,6-tetrα-O-acetyl-α-D-glucopyranosyl)-(l->4) -O- (2,3, 6-tri-O-acetyl-α-D-glucopyranosyl) - (1→-4) -2,3,6-tri-O-acetyl-l-thio-β-D-glucopyranoside (145)
Compound 144 (13 g, 13.5 mmol) is dissolved in toluene (80 ml). Ethanethiol (1.97 ml, 26.9 mmol) and boron trifluoride diethyl etherate (13.7 ml of a one molar solution in toluene) is added under a nitrogen atmosphere. After stirR1ng for 60 hours, the mixture is diluted with water and dichloromethane. After extraction, the organic phase is washed with 10% sodium hydrogen carbonate solution and water, dried, filtered and concentrated. The crude product is purified by chromatography on a column of silica gel to give 8.6 g of compound 145.
TLC: Rf = 0,60, silica gel, 7/3 v/v dichloromethane/ethyl acetate
PREPARATION 130
Ethyl O-(α-D-glucopyranosyl)- (l->4)-O-(α-D-
glucopyranosyl) - (l->4) -1-thio-β-D-glucopyranoside (146)

Compound 145 is converted into compound 146 according to the procedure descR1bed for the preparation of compound 95.
TLC: Rf = 0.80, silica gel, 13/7/1.6/4 v/v/v/v ethyl acetate/pyridine/acetic acid/water
PREPARATION 131
Ethyl O- (2,3,4,6-tetra-O-benzoyl-α-D-glucopyranosyl)-(l-»4)-O-(2,3,6-tri-O-benzoyl-α-D-glucopyranosyl)-(1^4)-2,3,6-tri-O-benzoyl-l-thio-β-D-glucopyranoside (147)
Compound 146 is converted into compound 147
according to the procedure descR1bed for the
preparation of compound 92.
TLC: Rf = 0.50, silica gel, 9/1 v/v toluene/ethyl
acetate



PREPARATION 132
Methyl O-(2,3,4,6-tetra-O-benzoyl-α-D-glucopyranosyl)-(1-^4)-O-(2,3,6-tri-O-benzoyl-α-D-glucopyranosyl)-(1^4)-O- (2,3,6-tri-O-benzoyl-β-D-glucopyranosyl)-(l->4)-O-(6-O-benzoyl-2,3-di-O-methyl-α-D-glucopyranosyl)- (1^4) -O-(2,3, 6-tri-O-methyl-β-D-glucopyranosyl)- (l->4) - [O-(2,3, 6-tri-O-methyl-α-D-glucopyranosyl)- (1^'4) -O-(2,3, 6-tri-O-methyl-β-D-glucopyranosyl)-(l->4) ] 3-O-(6-O-acetyl-2,3-di-O-methyl-α-D-glucopyranosyl) - (1->4) -O- (benzyl 2, 3-di-O-methyl-β-D-glucopyranosyluronate) - (1→4) -O- (3-O-acetyl-2-O-benzyl-6-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (benzyl 2,3-di-O-methyl-α-L-idopyranosyluronate) - (1-^4) -2, S-di-O-benzyl-S-O-methyl-α-D-glucopyranoside (148)
The thioglycoside 147 (105 mg, 0.066 mmol) and the acceptor 142 (55 mg, 0.017 mmol), (α/β of 8/2) are coupled according to the procedure descR1bed for compound 109. The product is first purified by chromatography on Sephadex LH 20 (1/1 dichloro-methane/methanol) and then by chromatography on a column of silica gel (9/0.5/0.5 v/v/v diethyl ether/ethyl acetate/ethanol) to give 49 mg of compound 148.
TLC: Rf = 0.30, silica gel, 85/7.5/7.5 v/v/v diethyl ether/ethyl acetate/ethanol
PREPARATION 133
Methyl O-(2,3,4,6-tetrα-O-benzoyl-α-D-glucopyranosyl)-(l->4)-O- (2,3,6-tri-O-benzoyl-α-D-glucopyranosyl)-(l->4)-O-(2,3,6-tri-O-benzoyl-β-D-glucopyranosyl)-(l->4)-O-(6-O-benzoyl-2,3-di-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (l->4) - [O- (2,3, 6-tri-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyranosyl) - (1^^4) ] 3-O- (6-O-acetyl-2, 3-di-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2, 3-di-O-methyl-β-D-glucopyranosyluronic acid) - (1-^4)-O-(3-O-acetyl-6-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2, 3-di-O-methyl-α-

L-idopyranosyluronic acid) - (1→ 4)- 6-O-methyl-α ~ D- glucopyranoside (149)
A solution of compound 148 (47mg, 0.01 mmol) in ethyl acetate (10 ml) is stirred under a hydrogen atmosphere in the presence of 10 palladium-on charcoal (90 w/w relative to compound 148) for 3 hours and filtered. The filtrate is concentrated to give 42 mg of compound 149. TLC: Rf = 0.35, silica gel, 20/7/1-6/4 v/v/v/v ethyl acetate/pyridine/acetic acid/water
PREPARATION 134
Methyl O-(α-D-glucopyranosyl)-(l->4) -O-(α-D-
glucopyranosyl)- (l->4)-O-(p-D-glucopyranosyl)- (1-^4)-O-(2 ,3-di-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2,3,6-tri-O-methyl-β-D-rglucopyranosyl) - (l->4) - [O- (2,3, 6-tri-O-mathyl-α-D-gluGOpyranosyl) -(l->4) -O- (2,3, 6-tri-O-methyl-β-D-glucopyranosyl) -(l->4) ]3-O-(2,3-di-O-methYl-α-D-glucopyranosyl) - (l'->4) -O-(2,3-di-O-methyl-β-D-glucopyranosyluronic acid) - (l->4) -O- (6-O-methyl-α-D-glucopyranosyl) - (l->4) -O- (2 ,3-di-O-methyl-α-L-idopyranosyluronic acid) - (l->4) -6-O-methyl-α-β-gluco-pyranosidd (150)
A mixture of methanol (0,22 ml) and 0.65 N sodium hydroxide solution (0.66 ml) is added to compound 149 (41 mg, 0.01 mmol) followed by stirR1ng for 20 hours at room temperature. The mixture is diluted with water and acidified with a 0.5 N hydrochloR1c acid solution in order to obtain a pH of 6.5. After concentration, the pure product is desalinated on a column of Sephadex G-25, using 9/1 v/v water / actetonitrile. The hexadecasaccharide fractions are combined and freeze-dried to give 26 mg of compound 150 as an amorphous white powder.
TLC: Rf = 0.35, silica gel, 8/7/1.6/4 v/v/v/v ethyl acetate/pyridine/acetic acid/water.

PREPARATION 13 5 6-O-Tert-butyldimethylsilyl-l,2-O-isopropylidene-3-O-
methyl-α-D-glucofuranose (152)
The diol 151 (10 g, 42.7 mmol) is taken up in anhydrous dichloromethane (100 ml) and tert-butyldimethylsilyl chloride (7.1 g, 47.3 mmol) and imidazole (5.8 g, 85.3 mmol) are added. The reaction mixture is stirred at room temperature. After 2 hours, the mixture is diluted in dichloromethane and washed with water. The organic phase is dried over magnesium sulphate and concentrated and the residue is purified by chromatography on a column of silica gel (1/9 v/v ethyl acetate/cyclohexane) in order to obtain the desired product 152 (11.9 g, 80%) in the form of a syrup. [αlD -34o (c 1.9,CHCl3) .
PREPARATION 13 6
6-O-Tert-butyldimethylsilyl-l,2-O-isopropylidene-3-O-methyl-S-C-vinyl-α-D-glucofuranoae (154)
Oxalyl chloride (3.2 ml, 3 6.8 mmol) and dimethyl sulphoxide (5.2 ml, 73.4 mmol) are added, at - 78 °C, to anhydrous dichloromethane (40 ml) and the mixture is stirred for 3 0 minutes. Next, compound 152 (6.4 g, 18.4 mmol) is added and the mixture is stirred for a further 1 hour. triethylamine (15.3 ml, 110.0 mmol) is then added and, after 30 minutes, the reaction mixture is diluted in dichloromethane. Standard processing allows the 5-ulose compound (153) to be obtained, which is used directly for the following reaction. The crude ketone 153 is taken up in anhydrous tetrahydrofuran (100 ml) and IM vinyl-magnesium bromide solution in tetrahydrofuran (28 ml, 27,6 mmol) is added at 0°C. After 1 hour, the reaction mixture is diluted with ammonium chloride and washed with water. The organic phase is dried over magnesium sulphate and concentrated and the residue is purified by chromatography on a column of silica gel (1/9 v/v ethyl acetate/cyclohexane) in order to obtain the

desired compound 154 (70%, 4.8 g) in the form of a syrup.
[α]D -40° (c 1.3, CHCI3) .
Anal. calculated: C, 57.72, H, 9.15. Found: C, 51.11, H, 9.23.
PREPARATION 137
1,2,4,6-Tetra-O-acetyl-3-O-methyl-5-C-vinyl-β-D-
glucopyranose (156)
Compound 154 (3.5 g, 9.4 mmol) is taken up in water (50 ml); IR-120 resin (1 g) is added thereto and the mixture is heated at 80oC for 6 hours. The resin is filtered off and the filtrate is concentrated. The crude product 155 is acetylated using acetic anhydride (12 ml) and pyridine (13 ml) . The excess acetic anhydride is destroyed with methanol and the solvents are concentrated. The residue is extracted with water and dichloromethane. The organic phase is dried over magnesium sulphate, concentrated and, after purification by chromatography on a column of silica (3/2 v/v ethyl acetate/cyclohexane), the tetraacetate compound 156 is obtained in the form of a solid (75%, 2.7 g) . m.p. 50oC. [α]^ -84° (c 1.6, CHCI3) .
Anal, calculated: C, 52.47, H, 6.19. Found: C. 52.51, H, 6.19. Cl-MS: 406 (M + NHJ , 389 (M + 1) .
PREPARATION 138
Methyl 2,3,6-tri-O-benzyl-4-O-(2,4,6-tri-O-acetyl-3-O-methyl-5-C-vinyl-β-D-glucopyraulosyl) -α-D-glucopyranoside (158)
Compound 156 (1.5 g, 4,1 mmol) and compound 157
2.1 g, 4.5 mmol) (P.J. Garegg and H. Hultberg, Carbohydr. Res. 1981, 93, CIO) are dissolved in anhydrous dichloromethane (50 ml) and molecular sieves (4.0 g) are added. The reaction mixture is stirred at room temperature for one hour and TMSOTf (0.95 ml,
5.1 mmol) is then added at -78°C. The reaction mixture

is then left to warm slowly to room temperature. After 2 hours, the reaction mixture is neutralized with triethylamine and filtered through Celite; the filtrate is washed with water. The organic phase is dried over magnesium sulphate and concentrated and the residue is purified by chromatography on silica (4/1 v/v ethyl acetate/cyclohexane) in order to obtain the desired compound 158 (2.77 g, 85%) in the form of a solid, m.p. 47°C.
[α]D -36° (c 0.6, CHCI3) .
Anal, calculated: C, 65.14, H, 6.61. Found: C, 65.09, H, 6.70.
PREPARATION 139
Methyl 2,3,6-O-tri-O-benzyl-4-O-(4,6-O-isopropylidene-3-O-methyl-5-C-vinyl-β-D-glucopyranosyl) -α-D-gluco-pyranoside (160)
Compound 158 (2.7 g, 3.4 mmol) is dissolved in methanol (40 ml) . Sodium (catalytic) is added at 0'=*C and the mixture is stirred at room temperature for 3 hours. The solvent is concentrated and the residue 159 is taken up in anhydrous acetone (40 ml) and 2,2-dimethoxypropane (2 ml) and p-toluenesulphonic acid (catalytic) are added. The reaction mixture is stirred at room temperature overnight. The solvent is evaporated off and the residue is taken up in chloroform and washed with water. The organic phase is dried over magnesium sulphate and concentrated and the residue is purified by chromatography on a column of silica (1/1 v/v ethyl acetate/cyclohexane) in order to obtain the 4', 6'-isopropylidene-O- deR1vative 160 (1.7 g, 70%) in the form of a solid, m.p. 55*^0. [α]^ +13° (c 0.8, CHCI3) .
Anal, calculated: C, 67,97, H, 7.13. Found: C, 67.87, H, 7.15. Cl-MS: 707 (M + 1), 724 (M + NHJ .

PREPARATION 140
Methyl 2,3,6-tri-O-benzYl-4-O-(4,6-O-isopropylidene-3-O-methyl-5-C-vinyl-β-D-mannopyranosyl)-α-D-gluco-pyranoside (162)
Oxalyl chloride (0.35 ml, 4,0 mmol) and anhydrous DMSO (0.57 ml, 8.0 mmol) in anhydrous dichloromethane (10 ml) are stirred at -78°C for 30 minutes. Compound 160 (1.4 g, 2.0 mmol) in anhydrous dichloromethane (10 ml) is added to the solution and the mixture is stirred for a further 45 minutes. The reaction mixture is neutralized by addition of anhydrous triethylamine (1.7 ml, 12,0 mmol) and is then diluted with dichloromethane. After washing with water, the organic phase is dried over magnesium sulphate and concentrated and the residue 161 is used directly for the following reaction without purification. The ketone 161 is taken up in anhydrous tetrahydrofuran (15 ml) and a IN solution of super hydride in tetrahydrofuran (4 ml, 4.0 mmol) is added at -78°C. The reaction mixture is stirred at room temperature for 1 hour and 5% sodium hydroxide (2 ml) and hydrogen peroxide (1 ml) are then added. The solvent is evaporated off and the residue is taken up in ethyl acetate and washed with water. The organic phase is dried over magnesium sulphate and concentrated and the residue is purified by chromatography (2/1 v/v ethyl acetate/cyclohexane) in order to obtain compound 162 (1,0 g, 70%). [α]D -11^ (c 0,5, CHCI3) . Cl-MS: 724 (M + 18), 707 (M + 1).
PREPARATION 141
Methyl 2,3,6-tri-O-benzyl-4-O-(2-O-acGtyl-3-O-methyl-5-
C-vinyl-β-D-mannopyranosyl)-α-D-glucopyranoside (164)
Compound 162 (940 mg, 1.3 mmol) is dissolved in pyridine (3 ml) and acetic anhydride (0.3 ml) is added. The reaction mixture is stirred at room temperature for 3 hours. The excess pyridine and acetic anhydride is evaporated off and the residue 163 is used directly for the deprotection of the isopropylidene using 80% acetic

acid (5 ml) at 60°C for 2 hours. The excess acetic acid is evaporated off and the residue is purified by chromatography on a column of silica gel (4/1 v/v ethyl acetate/cyclohexane) in order to obtain the diol 164 (660 mg, 70%) in the form of a solid, m.p. 53^C. [α]^ -10^ (c 0.8, CHCI3) . Cl-MS: 709 (M + 1), 726 (M + 18).
PREPARATION 142
Methyl 2,3,6-tri-O-benzyl-4-(2-O-acetyl-3-O-methyl-6-O-
tosyl-5-C-vinyl-β-D-mannopyranosyl)-α-D-glucopyranose
(165)
Compound 164 (600 mg, 0.9 mmol) is dissolved in pyridine (3 ml) and tosyl chloride (240 mg, 1.3 mmol) is added. The reaction mixture is stirred at room temperature for 3 hours. The solvent is evaporated off and the residue is diluted with chloroform and washed with water. The organic phase is dried over magnesium sulphate and concentrated and the residue is purified by chromatography on a column of silica gel (l/l v/v ethyl acetate/cyclohexane) in order to obtain the tosyl compound 165 (297 mg, 80%) in the form of a syrup, [α]^ -26*^ (c 0.8, CHCI3) .
PREPARATION 143
Methyl 2,3,6-tri-O-benzyl-4-(2,6-anhydro-3-O-methyl-5-C-vinyl-β-D-lnannopyrallosyl) -α-D-glucopyranoside (166)
Compound 165 (550 mg, 0.6 mmol) is taken up in ethanol (3 ml) and a 0. IN solution of ethanolic sodium hydroxide (5 ml) is then added. The reaction mixture is heated at 70°C for 3 hours and then neutralized with IR-12 0 resin (H* form) and filtered through Celite. After concentration, the residue is purified by chromatography on a column of silica gel (1/1 v/v ethyl acetate/cyclohexane) in order to obtain compound 166
(292 mg, 70%) in the form of a syrup.
[α]^ +13° (c 0.5, CHCI3) . Cl-MS: 666 (M + 18).

PREPARATION 144
Methyl 2,3,6-tri-O-benzyl-4-(benzyl 3-O-methyl-2-O-5-C-methylidene-α-L-idopyranuronate)-α-D-glucopyranoside (167)
Compound 166 (260 mg, 0.4 mmol) is dissolved in dichloromethane (20 ml) , the solution is stirred at -78°C and ozone is then bubbled through for 30 seconds. The colour of the solution becomes pale yellow. Dimethyl sulphide is added to the solution and the reaction mixture is then washed with water. The organic phase is dried over magnesium sulphate and concentrated and is passed directly into the following reaction without further purification. The crude aldehyde is taken up in tert-butanol (16 ml) and 2-methyl-2-butene (5 ml) and water (16 ml) are added. NaH2PO4 (700 mg) and NaClO2 (700 mg) are then added successively to the mixture. The suspension is stirred vigorously at room temperature overnight, diluted with water and extracted with ethyl acetate. The organic phase is dried over magnesium sulphate, concentrated and then passed directly into the following reaction. The crude acid is taken up in dimethyl formamide (25 ml) and tetrabutylammonium iodide (0.7 g, 2.0 mmol), potassium bicarbonate (0.25 g, 2.5 mmol) and benzyl bromide (0.250 ml, 2.1 mmol) are added. The reaction mixture is stirred at room temperature for 5 hours. The reaction mixture is extracted with water and ether. The ether phase is dried over magnesium sulphate and concentrated and the residue is purified by chromatography on a column of silica gel (2/1 v/v ethyl acetate/cyclohexane) in order to obtain the deR1vative 167 (236 mg, 80%) in the form of a syrup. Cl-MS: 774 (M + 18).







Methyl O-(3-O-methyl-2,4,6-tri-O-sulpho-α-D-glucopyrano-syl)-(1-4)-O-(3-O-methyl-2,6-di-O-sulpho-β-D-gluco-pyranosyl)-(1-4)-[O-(3-O-methyl-2,6-di-O-sulpho-α-D-glucopyranosyl)-(1-4)-O-(3-O-methyl-2,6-di-O-sulpho-p -D-glucopyranosyl) -(l-4)]5-O-(2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl)-(l-4)-O-(2,3-di-O-methyl-β-D-glucopyranosyluronic acid)-(1-4)-O-(2,3,6-tri-O-sulpho-α-D-glucopyranosyl)-(1-4)-O-(2,3-di-O-methyl-α-L-idopyranosyluronic acid)-(1-4)-2,3,6-tri-O-sulpho-α-D-glucopyranoside, sodixim salt (168) .
Compound 31 is treated according to Method 5 in order to give 168 (80 % over the three steps). [α]^ + 41 (c = 0.8, water). ESIMS, negative mode: monoisotopic mass = 7133.26; chemical mass = 7138.90; expeR1mental mass = 7137.26 ± 0.0 a.m,u, 1H NMR (D2O) 5 of the main anomeR1c protons: 5.71; 5.48; 5.46; 5.44; 5/17; 5,08; 4.81; 4.78; 4.67 ppm.
An identical procedure allows compounds 169 and 170 to be obtained.



EXAMPLE 4
Methyl O- (2, 3-di-O-methyl-4, 6-di-O-sulpho-α-D-gluco-pyranosyl) -(1-4)-[O-(2, 3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl) - (1-4) ] 15-O- (2, 3-di-O-methyl-β-D-glucopyranosyluronic acid)-(1-4) -O-(2,3,6-tri-O-sulpho-α-D-glucopyranosyl) - (1-4) -O- (2, 3-di-O-methyl-α-L-idopyranosyluronic acid)-(1-4)-2,3,6-tri-O-sulpho-α-D-glucopyranoside, sodium salt (171) .
Compound 51 (55 mg, 10.5 mmol) is treated according to Method 5 in order to obtain, after freeze-drying, the sulpha ted product 187 (50 mg^ 77 % over three steps). [α]^ + 107 (c = 0.52, water). ESIMS, positive mode: monoisotopic mass = 6194.16; chemical mass = 6198.83; expeR1mental mass = 6195.33 ± 1.79, 1H NMR (D2O) 5 of the main anomeR1c protons: 5.71; 5.67; 5.48; 5.43; 5.17; 5.10; 4.68 ppm.
An identical procedure allows compounds 172 and 173 to be obtained.



EXAMPLE 7
Methyl O-(3-O-methyl-2,4,6-tri-O-sulpho-α-D-glucopyran-osyl) - (1-4) -O- (3-O-methyl-2,6-di-O-sulpho-β-D-gluco-pyranosyl)-(1-4)-O-(3-O-methyl-2,6-di-O-sulpho-α-D-glucopyranosyl)-(1-4)-O-(3-O-methyl-2,6-di-O-sulpho-β-D-glucopyranosyl)-(1-4)-[O-(2,3,6-tri-O-methyl-α-D-glucopyranosyl)-(1-4)-O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl) - (1-4) ] ^-O- (2, S-di-O-methyl-S-O-sulpho-α-D-glucopyranosyl) -(1-4)-O-(2,3-di-O-methyl-β-D-glucopyranosyluronic acid)-(1-4)-O-(2,3,6-tri-O-sulpho-α-D-glucopyranosyl) - (1-4)-O-(2,3-di-O-methyl-α-L-idopyranosyluronic acid)-(1-4)-2,3,6-tri-O-sulpho-α-D-glucopyranoside, sodium salt (174).
Compound 75 is treated according to Method 5 in order to give 174 (84 % over the three steps) . [α]^ + 62 (c - 0.46, water). ESIMS, positive mode: monoisotopic mass = 4966.39; chemical mass = 4970.04; expeR1mental mass = 4969.63 ± 0.78 a.m.u. 1H NMR (DjO) 5 of the main anomeR1c protons: 5.69; 5.63; 5.57; 5.46; 5.44; 5,41; 5.15; 5.06; 4.79; 4.66; 4.62; 4.41 ppm.
By working according to Example 7 and using suitable intermediates, Examples 3 to 12 descR1bed in Table III below are prepared.



EXAMPLE 13
Methyl O-(2,3,4,6-tetrα-O-sulpho-α-D-glucopyranosyl)-(1->4)-O-(2,3,6-tri-O-sulpho-α-D-glucopyranosyl)-(l->4) -O-(2,3,6-tri-O-sulpho-β-D-glucopyranosyl)- (l->4) -O-(2,3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl) - (l->4) -O-(2,3, 6-tri-O-methyl-(J-D-glucopyranosyl) - (l->4) - [O-(2, 3, 6-tri-O-methyl-α-D-glucopyranosyl) - (l->4) -O-(2,3,6-tri-O-methyl-β-D-glucopyranosyl) - (l->4)]3-O- (2,3-di-O-methyl-6-O-sulpho-α-D-glucopyranosyl) - (1">4) -O-(2, 3-di-O-methyl-β-D-glucopyranosyluronic acid) - (l->4) -O-(6-O-methyl-2,3-di-O-sulpho-α-D-glucopyranosyl)-(l->4)-O-(2,3-di-O-methyl-α-L-idopyranosyluronic acid)-(l->4)-6-O-methyl-2,3-di-O-sulpho-α-D-glucopyranoside (180)
The fully deprotected hexadecasaccharide 150 (26 mg, 0.0084 mmol) is dissolved in dimethylformamide (0.87 ml). Sulphur trioxide/triethylamine complex (125 mg, 0.67 mmol, 80 eq) is added, under a nitrogen atmosphere, and the mixture is stirred for 16 hours at 50*^C. The mixture is cooled to 0°C and aqueous sodium hydrogen carbonate (227 mg, 2.6 mmol) are added. The mixture is concentrated to a small volume and placed on a Sephadex G-25 column, eluted with 9/1 v/v water/acetonitrile. The appropR1ate fractions are separated, concentrated to a small volume, placed on a Dowex XW4 Na+ ion-exchange column in water and the eluate is freeze-dried to give 37 mg of compound 151 as a white powder, [α]20D = +67,6 (c = 1, water) MS ESI: molecular weight is 4370.6 (H+ form) C12BH222O113S16 (Theor. m.w. = 4370.14).
NMR; shift of the anomeR1c protons (ppm): unit 1: 5.17; unit 2 : 5 . 03; unit 3 : 5.41; unit 4 : 4 .42 unit 5: 5.49; unit 6: 4.66; units 7, 9 and 11: 5.67 units 8, 10 and 12: 4.46; unit 13: 5.61; unit 14: 4.94 unit 15: 5.59 ppm; unit 16: 5.69.




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Patent Number 222507
Indian Patent Application Number 1575/MAS/1997
PG Journal Number 47/2008
Publication Date 21-Nov-2008
Grant Date 14-Aug-2008
Date of Filing 14-Jul-1997
Name of Patentee SANOFI-SYNTHELABO
Applicant Address 174 AVENUE DE FRANCE, 75013 PARIS,
Inventors:
# Inventor's Name Inventor's Address
1 GROOTENHUIS PETER VAN DER DUYN VAN, MAASDAMSTRAAT, 48 5344 HS OSS PAYS BAS,
2 DRIGUEZ PIERRE ALEXANDRE 7 AVENUE JULES JULIEN, 31400 TOULOUSE,
3 DUCHAUSSOY PHILIPPE 37, RUE LAGANNE, 31300 TOULOUSE,
4 HERBERT JEAN MARC 10 RUE DE 1 AMANDIER, 31170 TOURNEFEUILLE,
5 PETITOU MAURICE TOUR MEXICO, 65, RUE DU JAVELOT, 75645 PARIS, CEDEX 13,
6 VAN BOECKEL CONSTANT MERCURIUSSTRAAT 32, 5345 LX OSS PAYS-BAS,
PCT International Classification Number C08B 37/00
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 96 09116 1996-07-19 France