| Title of Invention | "A PROCESS FOR THE PREPARATION OF A TAXOID" |
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| Abstract | : This invention relates to the preparation of taxoid of formula I wherein Z,R1 to R7 are as defmed in the claim 1 which process comprises reacting R4-y, in which y is a leaving group & R4 is as defined in Claim 1 with 10-hydroxy group of compound of formula V wherein Zb R5,RS,R7 are defined in claim -1 in which the hydroxyl function at 10-postion is metal led by means of an alkali metal hydride amide or alkylide, in which the compound of general formula (V), Z1 represents a hydrogen atom or a group protecting the hydroxyl function or a radical of general formula (VI) in which R1 and R3 are as define above and R6 represents a group protecting the hydroxyl function, Rs and R6 represent hydrogen atoms and R and R7 together from a bond to obtain a corresponding compound in which the 10-hydroxy group in the compound of general formula (V) is replaced by a group R,; and (b) when the corresponding compound obtained in (a) contains a protecting group represented by Z1 or Rs by a hydrogen atom by means of an inorganic acid in an aliphatic alcohol containing 1 to 4 carbon atoms at a temperature of between -10 and 20°C or by means of the hydrofluoric acid/trithylamine complex, working in the inert organic solvent at a temperature of between 0 and 50°C to obtain a compound of formula (I) in which Z represents a hydrogen atom or a radical of general formula (II). |
| Full Text | This application is a divisional application out of patent application number 2893/Del/96 filed on December 20, 1996. The present invention relates to a process for the preparation of a taxoid and also relates to taxoid of general formula (I) (Formula Removed) in whichs Z represents a hydrogen atoJa or a radical of general formula: (Formula Removed) in whichs Rj represents a benzoyl radical optionally substituted by one or more identical or different atoms or radicals chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms, allcoxy radicals, containing 1 to 4 carbon atoms or trifluoromethyi radicals* a thenoyl or furoyl radical or a radical R2-0-C0~ in which R2 represents an alJtyl radical containing 1 to 8 carbon a totes, an alkenyl radical containing 2 to 8 carbon atoms, an alJcynyl radical containing 3 to 8 carbon atoms, a cycloalkyl radical containing 3 to 6 carbon atoms, a cycloalkenyl radical containing 4 to 6 carbon atoms or a bicycloalkyl radical containing 7 to 10 carbon atoms, these radicals being optionally substituted by one or more atoms or radicals chosen from halogen atoms and hydroxyl radicals, alkoxy radicals containing l to 4 carbon atoms, dialkylamino radicals in which each alkyl portion contains 1 to 4 carbon atoms, piperidino or morpholino radicals, l-piperazinyl radicals (optionally substituted at the 4-position by an alkyl radical containing 1 to 4 carbon atoms or by a phenylalkyl radical in which the alkyl portion contains 1 to 4 carbon atoms), cycloalkyl radicals containing 3 to 6 carbon atoms, cycloalkenyl radicals containing 4 to 6 carbon atoms, phenyl radicals (optionally substituted by one or more atoms or radicals chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms or alkoxy radicals containing 1 to 4 carbon atoms), cyano radicals, carboxyl radicals or alkoxycarbonyl radicals in which the alkyl portion contains 1 to 4 carbon atoms, a phenyl or α- or ß-naphthyl radical optionally substituted by one or more atoms or radicals chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms or alkoxy radicals containing 1 to 4 carbon atoms, or a 5-membered aromatic heterocyclic radical preferably chosen from furyl and thienyl radicals, or a saturated heterocyclic radical containing 4 to 6 carbon atoms, optionally substituted by one or more alkyl radicals containing 1 to 4 carbon atoms, R3 represents an alkyl radical containing 1 to 8 carbon atoms, an alkenyl radical containing 2 to 8 carbon atoms, an alkynyl radical containing 2 to 8 carbon atoms, a cycloalkyl radical containing 3 to 6 carbon atoms, cycloalkenyl radicals containing 4 to 6 carbon atoms, a phenyl or a- or ß-naphthyl radical optionally substituted by one or more atoms or radicals chosen from halogen atoms and alkyl, alkenyl, alkynyl, aryl, aralkyl, alkoxy, alkylthio, aryloxy, arylthio, hydroxy1, hydroxyalkyl, mercapto, formyl, acyl, acylamino, aroylamino, alkoxycarbonylamino, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, cyano, nitro and trifluoromethyl radicals, or a 5-membered aromatic heterocycle containing one or more identical or different hetero atoms chosen from nitrogen, oxygen and sulphur atoms and optionally substituted by one or more identical or different substituents chosen from halogen atoms and alkyl, aryl, alkoxy, aryloxy, amino, alkylamino, acylamino, dialkylamino, alkoxycarbonylamino, acyl, arylcarbonyl, cyano, carboxyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl or alkoxycarbonyl radicals, on the understanding that, in the substituents of the phenyl, α- or ß-naphthyl and aromatic heterocyclic radicals, the alkyl radicals and the allcyl portions of the other radicals contain 1 to 4 carbon atoms, and that the alkenyl and alkynyl radicals contain 2 to 8 carbon atoms, and that the aryl radicals are phenyl or α or ß-naphthyl radicals, either R4 represents a hydrogen atom, R6 and R7 together form a ketone function, and R and Rs together form a bond, or R4 represents a Hydrogen atom or a hydroxy! radical or an alkoxy radical containing 1 to 6 carbon atoms, an alkenyloxy radical containing 3 to 6 carbon atoms, an alkynyloxy radical containing 3 to 6 carbon atoms, a cycloalkyloxy radical containing 3 to 6 carbon atoms, a cycloalkenyloxy radical containing 3 to 6 carbon atoms, an alkanoyloxy radical in which the alkanoyl portion contains 1 to 6 carbon atoms, an aroyloxy radical in which the aryl portion contains 6 to 10 carbon atoms, an alkenoyloxy radical in which the alkenoyl portion contains 3 to 6 carbon atoms, an alkynoyloxy radical in which the alkynoyl portion contains 3 to 6 carbon atoms, a cycloalkanoyloxy radical containing 3 to 6 carbon atoms, an alkoxyacetyl radical in which the alkyl portion contains 1 to 6 carbon atoms, an alkylthioacetyl radical in which the alkyl portion contains 1 to 6 carbon atoms or an alkyloxycarbonyloxy radical in which the alkyl portion contains 1 to 6 carbon atoms, these radicals being optionally substituted by one or more halogen atoms or with an alkoxy radical containing l to 4 carbon atoms, an alkylthio radical containing 1 to 4 carbon atoms or a carboxyl radical, an alkyloxycarbonyl radical in which the alkyl portion contains 1 to 4 carbon atoms, a cyano or carbamoyl radical or an N-alkylcarbamoyl or N,N-dialkylcarbamoyl radical in which each alkyl portion contains 1 to 4 carbon atoms or, with the nitrogen atom to which it is linked, forms a saturated 5- or 6-membered heterocyclic radical optionally containing a second hetero atom chosen from oxygen,, sulphur and nitrogen atoms, optionally substituted by an alkyl radical containing 1 to 4 carbon atoms or a phenyl radical or a phenylalkyl radical in which the alkyl portion contains 1 to 4 carbon atoms, or alternatively R4 represents a carbamoyloxy or alkylcarbamoyloxy radical in which the alkyl portion contains 1 to 4 carbon atoms, a dialkylcarbamoyloxy radical in which each alkyl portion contains 1 to 4 carbon atoms or a benzoyloxy radical or a heterocyclylcarbonyloxy radical in which radical the heterocyclic portion represents a 5- or 6-membered aromatic heterocycle containing one or more hetero atoms chosen from oxygen, sulphur and nitrogen atoms, R5 represents a hydrogen atom or R4 and R5 together form a ketone function, R6 represents a hydrogen atom, and R and R7 together form a bond. Where a group is substitutled by more than one substituent, the substituents may be the same or different. The alkyl, alkenyl and alkynyl groups and moieties of groups may be present as straight or branched chains. Preferably, the aryl radicals which can be represented by R3 are phenyl or a- or /3-naphthyl radicals optionally substituted by one or more atoms or radicals chosen from halogen atoms (fluorine, chlorine, bromine, iodine) and alkylf alkenyl, alkynyl, aryl, arylalkyl, alkoxy, alkylthio, aryloxy, arylthio, hydroxyl, hydroxyalkyl, mercapto, formyl, acyl, acylamino, aroylamino, alkoxycarbonylamino, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, carbamoyl, dialkylcarbamoyl, cyano, nitro and trifluoromethyl radicals, on the understanding that the alkyl radicals and the alkyl portions of the other radicals contain 1 to 4 carbon atoms, that the alkenyl and alkynyl radicals contain 2 to 8 carbon atoms and that the aryl radicals are phenyl or α- or ß-naphthyl radicals. Preferably, the heterocyclic radicals which can be represented by R3 are 5-membered aromatic heterocyclic radicals containing one or more identical or different atoms chosen from nitrogen, oxygen and sulphur atoms, optionally substituted by one or more identical or different substituents chosen from halogen atoms (fluorine, chlorine, bromine, iodine) and alkyl radicals containing 1 to 4 carbon atoms, aryl radicals containing 6 to 10 carbon atoms, alkoxy radicals containing 1 to 4 carbon atoms, aryloxy radicals containing 6 to 10 carbon atoms, amino radicals, alkylamino radicals containing 1 to 4 carbon atoms, dialkylamino radicals in which each alkyl portion contains 1 to 4 carbon atoms, acylamino radicals in which the acyl portion contains 1 to 4 carbon atoms, alkoxycarbonylamino radicals containing 1 to 4 carbon atoms, acyl radicals containing 1 to 4 carbon atoms, arylcarbonyl radicals in which the aryl portion contains 6 to 10 carbon atoms, cyano, carboxyl or carbamoyl radicals, alkylcarbamoyl radicals in which the alkyl portion contains 1 to 4 carbon atoms, dialkylcarbamoyl radicals in wni.ch each alkyl portion contains 1 to 4 carbon atoms or alkoxycarbonyl radicals in which the alkoxy portion contains 1 to 4 carbon atoms. More especially, the present invention relates to the taxoids of general formula (I) in which Z represents a hydrogen atom or a radical of general formula (II) in which R5 represents a benzoyl radical or a radical R2-o-CO- in which R2 represents a tert-butyl radical and R3 represents an alkyl radical containing 1 to 6 carbon atoms, an alkenyl radical containing 2 to 6 carbon atoms, a cycloalkyl radical containing 3 to 6 carbon atoms, a phenyl radical optionally substituted by one or more identical or different atoms or radicals chosen from halogen atoms (e.g. fluorine, chlorine) and alkyl (e.g. methyl), alkoxy (e.g. methoxy), dialkylamino (e.g. dimethylami.no) , acylamino (e.g. acetylamino), alkoxycarbonylamino (e.g. tert-butoxycarbonylamino) or trifluoromethyl radicals, or a 2- or 3-furyl, 2- or 3-thienyl or 2-, 4- or 5-thiazolyl radical, and either R4 represents a hydrogen atom, R6 and R7 together form a ketone function and R and R5 together form a bond, or R4 represents a hydroxyl radical or an alkoxy radical containing 1 to 6 carbon atoms, an alkanoyloxy radical containing 1 to 6 carbon atoms or an alkoxyacetyl radical in which the alkyl portion contains 1 to 6 carbon atoms, Rs represents a hydrogen atom, R6 represents a hydrogen atom and R and R7 together form a bond, or R4 and Rs together form a ketone function, R6 represents a hydrogen atom, R and R7 together form a bond. Still more especially, the present invention relates to the taxoids of general formula (I) in which Z represents a hydrogen atom or a radical of general formula (II) in which R1 represents a benzoyl radical or a radical R2-Q-CG~ in which R2 represents a tert-butyl radical and R3 represents an isobutyl, isobutenyl, butenyl, cyclohexyl, phenyl, 2-furyl, 3-furyl, 2~thienyi, 3-thienyl, 2-thiazolyl, 4-thiasolyl or 5-thiazolyl radical, either R4 represents a hydrogen atom, R6 and R7 together form a ketone function and R and R5 together form a bond, or R4 represents a hydroxyl radical or a methoxy, acetoxy or methoxyacetoxy radical, R5 represents a hydrogen atom, R6 represents a hydrogen atom and R and R7 together form a bond. The taxoids of general formula (I) in which Z represents a radical of general formula (II) display noteworthy antitumour and antileukaemic properties. According to the invention, the taxoids of general formula (I) in which either R4 represents a hydrogen atom, R6 and R7 together form a ketone function and R and R5 together form a bond, or R4 represents a hydroxy1 radical, Rs represents a hydrogen atom, R6 represents a hydrogen atom and R and R7 together form a bond may be obtained by the action of a reducing agent on a compound of general formula (Formula Removed) in which Z, represents a hydrogen atom or a group protecting the hydroxyl function or a radical of general formula: (Formula Removed) in which R8 represents a group protecting the hydroxyl function, and X represents, with the! oxygen atom to which it is linked, a leaving group chosen from alkylsulphonyl radicals containing 1 to 4 carbon atoms optionally substituted by one or more halogen atoms, or arylsulphonyl radicals in which the aryl portion is a phenyl radical optionally substituted by one or more identical or different atoms or radicals chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms, or nitro or trifluoromethyl radicals, to obtain a compound of general formula:(Formula Removed)in which Z,, R, R4, R5, R6 and R, are as defined above, followed, if necessary, by the replacement of the protective group represented by Z1 or R8 by a hydrogen atom. Accordingly, there is provided a process for the preparation of a taxoid of general formula (I) (Formula Removed) in which: Z represents a hydrogen atom or a radical of general formula: (Formula Removed) in which: R1 represents a benzoyl radical optionally substituted by one or more identical or different atoms or radicals chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms, alkoxy radicals containing 1 to 4 carbon atoms or trifluoromethyl radicals, a thenoyl or furoyl radical or a radical R2-O-CO- in which R2 represents an alkyl radical containing 1 to 8 carbon atoms, an alkenyl radical containing 2 to 8 carbon atoms, an alkynyl radical containing 3 to 8 carbon atoms, a cycloalkyl radical containing 3 to 6 carbon atoms, a cycloalkenyl radical containing 4 to 6 carbon atoms or a bicycloalkyl radical containing 7 to 10 carbon atoms, these radicals being optionally substituted by one or more atoms or radicals chosen from halogen atoms and hydroxy1 radicals, alkoxy radicals containing 1 to 4 carbon atoms, dialkylamino radicals in which each alkyl portion contains 1 to 4 carbon atoms, piperidino or morpholino radicals, 1-piperazinyl radicals (optionally substituted at the 4-position by an alkyl radical containing 1 to 4 carbon atoms or by a phenylalkyl radical in which the alkyl portion contains 1 to 4 carbon atoms), cycloalkyl radicals containing 3 to 6 carbon atoms, cycloalkenyl radicals containing 4 to 6 carbon atoms, phenyl radicals (optionally substituted by one or more atoms or radicals chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms or alkoxy radicals containing 1 to 4 carbon atoms), cyano radicals, carboxyl radicals or alkoxycarbonyl radicals in which the alkyl portion contains 1 to 4 carbon atoms, a phenyl or a- or ß-naphthyl radical optionally substituted by one or more atoms or radicals chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms or alkoxy radicals containing 1 to 4 carbon atoms, or a 5-membered aromatic heterocyclic radical, or a saturated heterocyclic radical containing 4 to 6 carbon atoms, optionally substituted by one or more alkyl radicals containing 1 to 4 carbon atoms, R3 represents an alkyl radical containing 1 tc 8 carbon atoms, an alkenyl radical containing 2 to 8 carbon atoms, an alkynyl radical containing 2 to 8 carbon atoms, a cycloalkyl radical containing 3 to 6 carbon atoms, cycloalkenyl radicals containing 4 to 6 carbon atoms, a phenyl or a- or p-naphthyl radical optionally substituted by one or more atoms or radicals chosen from halogen atoms and alkyl, alkenyl, alkynyl, aryl, aralkyl, alkoxy, alkylthio, aryloxy, arylthio, hydroxyl, hydroxyalkyl, mercapto, formyl, acyl, acylamino, aroylamino, alkoxycarbonylamino, amino, alkylamino, dialkylamino, carboxyl, alkoxycarbonyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, cyano, nitro and trifluoromethyl radicals, or a 5-membered aromatic heterocycle containing one or more identical or different hetero atoms chosen from nitrogen, oxygen and sulphur atoms and optionally substituted by one or more identical or different atoms or radicals chosen from halogen atoms and alkyl, aryl, alkoxy, aryloxy, amino, alkylamino, acylamino, dialkylamino, alkoxycarbonylamino, acyl, arylcarbonyl, cyano, carboxyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl and alkoxycarbonyl radicals, on the understanding that, in the substituents of the phenyl, a- or p-naphthyl and aromatic heterocyclic radicals, the alkyl radicals and the alkyl portions of the other radicals contain 1 to 4 carbon atoms, and that the alkenyl and alkynyl radicals contain 2 to 8 carbon atoms, and that the aryl radicals are phenyl or a- or p-naphthyl radicals. R4 represents an alkoxy radical containing 1 to € carbon atoms, an alkenyloxy radical containing 3 to 6 carbon atoms, an alkynyloxy radical containing 3 to 6 carbon atoms, a cycloalkyloxy radical containing 3 to 6 carbon atoms, a cycloalkenyloxy radical containing 3 to 6 carbon atoms, an alkanoyloxy radical in which the alkanoyl portion contains 1 to 6 carbon atoms, an aroyloxy radical in which the aryl portion contains 6 to 10 carbon atoms, an alkenoyloxy radical in which, the alkenoyl portion contains 3 to 6 carbon atoms, an alkynoyloxy radical in which the alkynoyl portion contains 3 to 6 carbon atoms, a cycloalkanoyloxy radical containing 3 to 6 carbon atoms, an alkoxyacetyl radical in which the alkyl portion contains 1 to 6 carbon atoms, an alkylthioacetyl radical in which the alkyl portion contains 1 to 6 carbon atoms or an alkyloxycarbonyloxy radical in which the alkyl portion contains 1 to 6 carbon atoms, these radicals being optionally substituted by one or more halogen atoms or with an alkoxy radical containing 1 to 4 carbon atoms, an alkylthio radical containing 1 to 4 carbon atoms or a carboxyl radical, an alkyloxycarbonyl radical in which the alkyl portion contains 1 to 4 carbon atoms, a cyano or carbamoyl radical or an N-alkylcarbamoyl or N,N-dialkylcarbamoyl radical in which each alkyl portion contains 1 to 4 carbon atoms or, with the nitrogen atom to which it is linked, forms a saturated 5- or 6-membered heterocyclic radical optionally containing a second hetero atom chosen from oxygen, sulphur and nitrogen atoms, optionally substituted by an alkyl radical containing 1 to 4 carbon atoms or a phenyl radical or a phenylalkyl radical in which the alkyl portion contains 1 to 4 carbon atoms, or alternatively R4 represents a carbaraoyloxy or alkylcarbamoloxy radical in which the alkyl portion contains 1 to 4 carbon atoms, a dialkylcarbamoyloxy radical in which each alkyl portion contains 1 to 4 carbon atoms or a benzoyloxy radical or a heterocyclylcarbonyloxy radical in which radical the heterocyclic portion represents a 5- or 6- membered aromatic heterocycle containing one or more hetero atoms chosen from oxygen, sulphur and nitrogen atoms, R5 represents a hydrogen atom, R6 represents a hydrogen atom, and R and R7 together form a bond, which process comprises: (a) reacting by known methods a compound of general formula: (Formula Removed) in which Y represents a leaving group and R4 as defined above with the 10-hydroxy group of a compound of general formula: (Formula Removed) or a corresponding compound in which the hydroxyl function at the 10-position is metalated by means of an alkali metal hydride, amide or alkylide, in which the compound of general formula (V), Zi represents a hydrogen atom or a group protecting the hydroxyl function or a radical of general formula (IV)(Formula Removed) in which Ri and R3 are as defined above and R8 represents; a group protecting the hydroxyl function, R5 and R6 represent hydrogen atoms and R and R7 together form a bond to obtain a corresponding compound in which the 10-hydroxy group in the compound of general formula (V) is replaced by a group R4; and (b) when the corresponding compound obtained in (a) contains a protecting group represented by Z1 or R5 by a hydrogen atom by means of an inorganic acid in an aliphatic alcohol containing 1 to 4 carbon atoms at a temperature of between -10 and 20° C or by means of the hydrofluoric acid/triethylamine complex, working in an inert oganic solvent at a temperature of between 0 and 50° C to obtain a compound of formula (I) in which Z represents a hydrogen atom or a radical of general formula (II). or a corresponding compound in which the hydroxyl function at the 10-position is metalated by means of an alkali metal hydride, amide or alkylide, in which the compound of general formula (V), Z1 represents a hydrogen atom or a group protecting the hydroxyl function or a radical of general formula (IV) (Formula Removed) in which R1 and R3 are as defined above and R5 represents; a group protecting the hydroxyl function, R5 and R6 represent hydrogen atoms and R and R7 together form a bond to obtain a corresponding compound in which the 10-hydroxy group in the compound of general formula (V) is replaced by a group R4; and (b) when the corresponding compound obtained in (a) contains a protecting group represented by Z1 or R5 by a hydrogen atom by means of an inorganic acid in an aliphatic alcohol containing 1 to 4 carbon atoms at a temperature of between -10 and 20° C or by means of the hydrofluoric acid/triethylamine complex, working in an inert oganic solvent at a temperature of between 0 and 50° C to obtain a compound of formula (I) in which Z represents a hydrogen atom or a radical of general formula (II). Generally, the reducing agent is chosen from aluminohydrides or borohydrides such as alkali or alkaline-earth metal borohydrides, such as sodium borohydride, in the presence of an aliphatic alcohol containing 1 to 4 carbon atoms such as ethanol, the reaction being carried out at a temperature of between 0 and 50°C, preferably about 20°C. Preferably, the protective group represented by Rs is chosen from groups which can be easily _II ' introduced and easily removed without affecting the rest of the molecule, such as silylated radicals such as the triethylsilyl radical. The replacement of the protective group by a hydrogen atom, when it represents a silylated radical, is generally performed by means of an inorganic acid such as hydrochloric acid in an aliphatic alcohol containing 1 to 4 carbon atoms, at a temperature of between -10 and 2 0"C, preferably about 0°C, or in the presence of a source of fluoride ions such as a hydrofluoric acid-triethylamine complex, working in an inert organic solvent such as a halogenated aliphatic hydrocarbon such as dichloromethane at a temperature of between 0 and 5 0°C, preferably about 20°C. This process generally leads to a mixture of a taxoid of general formula (I) in which R4 represents a hydrogen atom, R6 and R7 together form a ketone function, and R and R5 together form a bond, and of a taxoid of general formula (I) in which R4 represents a hydroxyl radical, Rs represents a hydrogen atom, R6 represents a hydrogen atom and R and R7 together form a bond, which are separated by the usual methods such as chromatography. The compound of general formula (III) may be obtained by the action of an oxidizing agent on a compound of general formula: (Formula Removed) in which Z1 and X are as defined above. Generally, the oxidizing agent is chosen from agents which make it possible to oxidize the secondary alcohol function without affecting the rest of the molecule, such as for example oxygen, ammonium peruthenate, manganese dioxide, copper acetate or pyridinium chloroohromate. Preferably, pyridinium chlorochromate is used, working in an organic solvent such as optionally halogenated aliphatic hydrocarbons such as dichloromethane, at a temperature of between 0 and 50°C, preferably about 2 5°C. The compound of general formula (VI) in which Zj and X are as defined above may be obtained by the action of a sulphonyl halide on a compound of general formula: (Formula Removed) in which Z1 is as defined above, The compound of general formula (VI) in which X preferably represents a trifluoromethylsulphonyl radical may be obtained by the action of a derivative of trifluoromethanesulphonic acid such as the anhydride or N-phenyl trifluoromethanesulphonimide in an inert organic solvent such as an optionally halogenated aliphatic hydrocarbon such as dichloromethane, working in the presence of an organic base such as pyridine or a tertiary aliphatic amine such as triethylamine, at a temperature of between -5 0 and 20°Cf on a compound of general formula (VII). The compound of general formula (VII) in which Zj represents a radical of general formula (IV), in which R8 is defined as above, may be obtained by the action of a silylating agent on a compound of general formula; (Formula Removed) in which R, and R3 are defined as above. Generally, a trialkylsilyl halide such as triethylsilyl chloride is used, working in an optionally halogenated hydrocarbon such as dichloromethane, in the presence of Ian organic base such as pyridine or a tertiary aliphatic amine such as triethylamine. The compound of general formula (VIII) in which R3 represents a phenyl radical and R2 represents a tert-butyl radical is known by the name of docetaxel. The docetaxel derivatives which correspond to the general formula (VIII) may be obtained under the conditions described in International Applications PCT WO 92/09589, WO 93/16060 and WO 94/12484. The compound of general formula (VII) in which Z, represents a hydrogen atom is 10-deactylbaccatin III which is extracted in a known manner from yew (Taxus baccata) leaves. According to the invention, the compounds of general formula (I) in which Z is as defined above, R4 represents an alkoxy radical containing 1 to 6 carbon atoms, an alkenyloxy radical containing 3 to 6 carbon atoms, an alkynyloxy radical containing 3 to 6 carbon atoms, a cycloalkyloxy radical containing 3 to 6 carbon atoms, a cycloalkenyloxy radical containing 3 to 6 carbon atoms, an alkanoyloxy radical in which the alkanoyl portion contains 1 to 6 carbon atoms, an aroyloxy radical in which the aryl portion contains 6 to 10 carbon atoms, an alkenoyloxy radical in which the alkenoyl portion contains 3 to 6 carbon atoms, an alkynoyloxy radical in which the alkynoyl portion contains 3 to 6 carbon atoms, a cycloalkanoyloxy radical containing 3 to 6 carbon atoms, an alkoxyacetyl radical in which the alkyl portion contains 1 to 6 carbon atoms, an alkylthioacetyl radical in which the alkyl portion contains 1 to 6 carbon atoms or an alkyloxycarbonyloxy radical in which the alkyl portion contains 1 to 6 carbon atoms, these radicals being optionally substituted by one or more halogen atoms or with an alkoxy radical containing 1 to 4 carbon atoms, an alkylthio radical containing l to 4 carbon atoms or a carboxyl radical, an alkyloxycarbonyl radical in which the alkyl portion contains 1 to 4 carbon atoms, a cyano or carbamoyl radical or an N-alkylcarbamoyl or N,N-dialkylcarbamoyl radical in which each alkyl portion contains 1 to 4 carbon atoms or, with the nitrogen atom to which it is linked, forms a saturated 5- or 6-membered heterocyclic radical optionally containing a second hetero atom chosen from oxygen; sulphur and nitrogen atoms, optionally substituted by an alkyl radical containing 1 to 4 carbon atoms or a phenyl radical or a phenylalkyl radical in which the alkyl portion contains 1 to 4 carbon atoms, or alternatively R4 represents a carbamoyloxy or alkylcarbamoyloxy radical in which the alkyl portion contains 1 to 4 carbon atoms, a dialkylcarbamoyloxy radical in which each alkyl portion contains 1 to 4 carbon atoms or a benzoyloxy radical or a heterocyclic radical attached to a carbonyloxy group in which radical the heterocyclic portion represents a 5- or 6-membered aromatic heterocycle containing one or more hetero atoms chosen from oxygen, sulphur and nitrogen atoms, Rs represents a hydrogen atom, R6 represents a hydrogen atom, and R and R7 together form a bond, may be obtained by the action of a compound of general formula: R'4-Y (IX) in which R'4 is such that R'4-0- is identical to R4 as defined above and Y represents a leaving group such as a halogen atom, on the compound of general formula (V) in which Z1, is as defined above, R4 represents a hydroxyl radical, R6 represents a hydrogen atom and R and R7 together form a bond. Generally, the action of a compound of general formula (IX) on the compound of general formula (V) defined above is performed, after optional metalation of the hydroxyl function at the 10-position by means of an alkali or alkaline-earth metal hydride such as sodium hydride, an alkali metal amide such as lithium diisopropylamide or an alkali metal alkylide such as n-butyllithium, working in an organic solvent such as dimethylformamide or tetrahydrofuran or pyridine, at a temperature of between 0 and 50°C, followed, if necessary, by the replacement of the group protecting the hydroxyl function Z1 or R8 under the conditions described above. When Z2 is different from a radical of general formula (IV), it is particularly advantageous to perform the reaction on a compound o'f general formula (V) in which Z2 represents a group protecting the hydroxyl function which is preferably a triethylsilyl radical. In this case, the protective group is introduced by the action of a trialkylsilyl halide, preferably triethylsilyl chloride, on a compound of general formula (VI) in which Z, represents a hydrogen atom. According to the invention, the compounds of general formula (I) in which Z represents a radical of general formula (II), R4 and R5 together form a ketone function, R6 represents a hydrogen atom, and R and R7 together form a bond, may be obtained by oxidation of a compound of general formula (V) in which Z1 is as defined above, R4 represents a hydroxyl radical, Rs represents a hydrogen atom, R6 represents a hydrogen atom and R and R7 together form a bond, followed, if necessary, by the replacement of the protective group represented by Z, or R8 by a hydrogen atom under the conditions described above. Generally, the oxidation is performed under the conditions described above for the oxidation of a compound of general formula (VI). According to the invention, the compounds of general formula (I) in which Z represents a radical of general formula (II), R4, R5 and R6 each represent a hydrogen atom and R and R7 together form a bond, may be obtained from a compound of general formula (V) in which Z, is as defined above, R4 represents a hydroxyl radical, R5 and R6 each represent a hydrogen atom and R and R7 together form a bond, after conversion of the hydroxyl radical represented by R4 to a dithiocarbonate followed by the reduction of the compound obtained by means of a trialkyltin hydride such as tributyltin hydride, followed, if necessary, by the replacement of the protective group represented by Z1 or R8 by a hydrogen atom under the conditions described above. According to the invention, the compounds of general formula (I) may also be obtained by esterification of a compound of general formula (I) in which Z represents a hydrogen atom by means of an acid of general formula? (Formula Removed) in which, either R9 represents a hydrogen atom and R10 represents a group protecting the hydroxyl function, or R, and R10 together form a saturated 5- or 6-membered heterocycle, or by means of a derivative of this acid, followed by the replacement of the group R10 and, where necessary, R9 by hydrogen atoms. The conditions for esterification and replacement of the protective groups are identical to those which are described, for example, in International Applications PCT WO 92/09589, WO 93/16060 and WO 94/12484. The taxoids of general formula {I) obtained by carrying out the processes according to the invention may be purified according to known methods such as crystallization or chromatography. The taxoids of general formula (I) in which Z represents a radical of general formula (II) display noteworthy biological properties. In vitro, measurement of the biological activity is performed on tubulin extracted from pig's brain by the method of M.L. Shelanski et al., Proc. Natl. Acad. sci. USA, 70), 765-768 (1973). Study of the depolymerization of microtubules to tubulin is performed according to the method of G. Chauviere et al., C.R. Acad. Sci., 293„ series II, 501-503 (1981). In this study,, the taxoids of general formula (I) in which Z represents a radical of general formula (II) were shown to be at least as active as Taxol and Taxotere. In vivo, the taxoids of general formula (I) in which Z represents a radical of general formula (II) were shown to be active in mice grafted with B16 melanoma at doses of between 1 and 10 mg/kg administered intraperitoneally, as well as on other liquid or solid tumours. The taxoids have antitumour properties, and more especially activity against tumours which are resistant to Taxol® or to Taxotere®.; Such tumours comprise colon tumours which have a high expression of the mdr 1 gene (multiple drug resistance gene). Multiple drug resistance is a customary term relating to the resistance of a tumour to different compounds having different structures and mechanisms of action. Taxoids are generally known to be strongly recognized by experimental tumours such as P388/D0X, a cell line selected for its resistance to doxorubicin EXAMPLE 1 117 mg of sodium borohydride are added to a solution of 0.65 g of 4α-acetoxy-2α-benzoyloxy-5ß 2 0-epoxy-lß-hydroxy-9, io-dioxo-7ß-trif luoromethane-sulphonyloxy-ll-taxen-13a-yl (2R, 3S)-3-tert-butoxy-carbonylamino-3-phenyl-2-triethylsilyloxypropionate in 6.5 cm3 of absolute ethanol maintained under an argon atmosphere at a temperature in the region of 2 0"C. After 5 minutes at a temperature in the region of 2 0 °C*, the reaction mixture is diluted with 5 0 cm3 of ethyl acetate. The organic phase is washed with 3 times 10 cm3 of distilled water and then with twice 10 cm3 of a saturated aqueous sodium chloride solution, dried over magnesium sulphate^, filtered through sintered glass and concentrated under reduced pressure (2.7 kPa) at a temperature in the region of 4 0°C. 60 0 mg of a white foam are thereby obtained which are combined with 313 mg of an identical crude mixture obtained from 500 mg of 4α-acetoxy-2α-benzoyloxy-5ß,20-epoxy-lß-hydroxy-9,10-dioxo-7ß-trifluoromethanesuiphonyloxy-ll-taxen-13a-yl (2R,3S)-3-tert-butoxycarbonylamino-3-phenyl-2-triethylsilyloxypropionate under the same conditions. The purification is performed by chromatography at atmospheric pressure on 100 g of silica (0.063-0.2 mm) contained in a column 3.5 cm in diameter, eluting with an ethyl acetate/dichloromethane mixture (elution gradient from 2-98 to 15-85 by volume), collecting 20-cm3 fractions. The fractions containing only the desired products are pooled and concentrated to dryness under reduced pressure (2.7 JcPa) at 40°C for 2 hours. 153 mg of 4a-acetoxy-2a-benzoyloxy-5/3/.2 0~epoxy-l/3-hydroxy-7a,10a-epoxy-9-oxo~ll-taxen-13a~yi (2R,38}-3-tert-butoxycarbonylamino-3-pheny1-2- triethylsilyloxypropionate are thereby obtained in the form of a white foam and 384 mg of 4α-acetoxy-2α-benzoyloxy-5ß,2 0-epoxy-lß, loß-dihydroxy-7α 9α-epoxy-Xl-taxen-l3a-yl (2R,3S)-3-tert~butoxycarbonylamino-3-phenyl-2-triethylsilyloxy-propionate in the form of a white foam. 4α-Acetoxy-2α-benzoyloxy-5ß, 2 0-epoxy-lß hydroxy-7α,10α-epoxy-9-oxo-ll-taxen-13a-yl (2R,3S)-3-tert-butoxycarbonylamino-3-pheny1-2-triethylsilyloxypropionate displays the following characteristics: - SH NMR spectrum (400 MH2; CDC13; S in ppm; coupling constants J in Hz): 0.34 and 0.41 (2 mts, 6H: CH2 of the triethylsilyl at position 2'); 0.77 (t, J = 7.5, 9 H: CH3 of the triethylsilyl at position 2'); 1.23 (s, 3H: CH3) ; 1.38 (s, 3H: CH3) ; 1.40 (s, 9H: C(GH3)3; 1.82 (s, 3H: CH3) ; 1.90 (s, 3H: CH3) ; 1.93 (s, IH: OH at positxon 1); from 2.15 to 2.40 (mt, 2H: CH2 at position 14); from 2.15 to 2.40 and 2.48 (2 mts, IH each: CH2 in position 6); 2.48 (s, 3H: COCH3) ; 3.70 (d, J = 8, IH: H at position 7); 4.2 5 and 4.32 (2 d, J = 8, IH each: CH2 at position 20); 4.58 (d, J = 7, IH: H at position 3); 4.59 (broad s, IH: H at position 2'); 4.86 (mt, IH: H at position 10); 5.11 (d, J = 5, IH: H at position 5); 5.32 (broad d, J = 10, IH: H at position 3'); 5.56 (d, J = 10, IH: CONH); 5.62 (d, J = 7, IH: H at position 2); 6.3 4 (broad t, J = 9, IH: H [lacuna]; from 7.2 5 to 7.45 (mt, 5H: aromatic H at position 3'); 7.50 (t, J = 7.5, 2H: OCOC6Hs H at the meta position); 7.62 (t, J = 7.5, IH: OCOC6Hs H at the para position); 8.13 (d, J = 7.5, 2H: OCOC6H5 H at the ortho position) . 4a-Acetoxy-2a-benzoyloxy-5/3,2 0-epoxy-1/3,10/3-dihydroxy-7a,9a-epoxy-ll-taxen-13a-yl (2R,3S)-3-tert-butoxycarbonylamino-3-phenyl-2- triethylsilyloxypropionate displays the following characteristics: - *H NMR spectrum (400 MHz; CDC13; S in ppm; coupling constants J in Hz): 0.3 3 and 0.4 0 (2 mts, 6H: CH2 of the triethylsilyl at position 2'); 0.75 (t, J = 7.5, 9H: CH3 of the triethylsilyl at position 2'); 1.13 (s, 3H: CH3) ; 1.27 (s, 3H: CH3) ; 1.37 (s, 9H: C(CH?)3); 1.75 (s, 3H: CH3) ; 1.85 (s, 1H: OH at position 1); 2.04 (s, 3H: CH3) ; 2.23 and from 2.30 to 2.50 (dd and mt respectively, J = 15 and 8, 1H each: CH2 at position 14); from 2.30 to 2.50 (mt, 2H; CH2 at position 6); 2.48 (s, 3H; C0CH3) ; 2.55 (d, J = 7, 1H: OH at position 10); 4.05 and 4.29 (2 d, J = 7.5, 1H each: CH2 at position 20); 4.17 (d, J = 6, 1H: H at position 3); 4.60 (broad s, 1H: H at position 2"); from 4.75 to 4.90 (mt, 3H: H at position 7 - H at position 9 and H at position 10); 4.97 (broad s, IHs H at position 5); 5.33 (broad d, J = 10, 1H: H at position 3'); 5.54 (d, J = 10, 1H: CONH); 5.80 (d, J = 6, 1H: H at position 2); 6.18 (broad t, J = 8, 1H: H at position 13); from 7.25 to 7.45 (mt, SH: aromatic H at position 3s); 7.49 (t, J = 7.5, 2H: OCOC6Hs H at the meta position); 7.62 (t, J = 7.5, 1H: OCOC6Hs H at the para position); 8.15 (d, J = 7.5, 2H: OCOC6H5 H at the ortho position). A solution of 12 6 mg of 4a-acetoxy-2a-benzoyloxy-5/3,20-epoxy-l/3,10j3-dihydroxy-7a,9a-epoxy-ll-taxen-13a-yl (2R,3S)-3-tert-butoxycarbonylamino-3-phenyl-2-triethylsilyloxypropionate in 1.7 cm3 of 0.1N ethanolic solution of hydrogen chloride is stirred, under an argon atmosphere, at a temperature in the region of 0°C, for 1 hour. The reaction mixture is then diluted with 2 0 cm3 of dichloromethane. The organic phase is washed with twice 5 cm3 of distilled water and then with twice 5 cm3 of a saturated'aqueous sodium chloride solution, dried over magnesium sulphate, filtered through sintered glass and concentrated under reduced pressure (2.7 kPa) at a temperature in the region of 40°C. 130 mg of an ivory-coloured foam are thereby obtained, which product is purified by preparative thin-layer chromatography [12 Merck preparative silica gel 6 0F2S4 platesz 20 x 20 cm; thickness 0.25 mm; application in solution in dichloromethane],, eluting twice with a methanol/ dichloromethane (5-95 by volume) mixture. After elution of the zone corresponding to the desired product with a methanol/dichloromethane (15-85 by volume) mixture, filtration through sintered glass and then evaporation of the solvent under reduced pressure (2.7 kPa) at a temperature in the region of 40°C, 22.6 mg of 4a-acetoxy-2a-benzoyloxy-5j3f 2 0-epoxy-l/3, 10/3~dihydroxy-7a,9a-epoxy-ll-taxen-13a-yl (2R,3S)-3-tert-butoxycarbonylamino-3-phenyl-2-faydroxypropionate are obtained in the form of a white foam, the characteristics of which are as follows: - *H NMR spectrum (400 MHz; CDC13; at a temperature of 333°K, S in ppm; coupling constants J in Hz): 1=14 (s, 3H: CH3) ; 1.25 (s, 3H: CH3) ; 1.40 (s, 9H: C(CH3)3); 1.74 (s, 3H: CH3) ; 1.86 (s, 1H: OH at position 1); 1.95 (s, 3H: CH3) ; from 2.15 to 2.45 (mt, 4Hs CH2 at position 14 and CH, at position 6); 2.33 (s, 3H: COCH3) ; 2.50 (unres. comp., 1H: OH at position 10); 3.67 (unres. comp., 1H: OH at position 2'); 4.0 6 and 4.2 7 (2 d, J = 7.5, 1H each: CH2 at position 20); 4.17 (d, J = 6, 1H: H at position 3); 4.65 (mt, 1H: H at position 2'); from 4.75 to 4.90 (mt, 3H: H at position 7 - H at position 9 and H at position 10); 4.93 (broad s, IHs H at position 5); 5.30 (broad d, J = 10, lH; H at position 3'); 5.50 (d, J = 10, 1H: CONH); 5.79 (d, J = 6, 1H: H at position 2); 6.06 (broad t, J = 9, 1H: H at position 13); 7.30 (t, J = 7.5, 1H: H at the para position of the aromatic at position 3'); 7.38 (t, J = 7.5, 2H: H at the meta position of the aromatic at position 3'); 7.44 (d, J = 7, 2Hs H at the ortho position of the aromatic at position 3'); 7.49 (t, J = 7.5, 2H; OCOC6Hs H at the meta position); 7.61 (t, J = 7.5, 1H: OCOC6Es H at the para position); 8.13 (d, J = 7.5, 2-H: OCOC6Hs H at the ortho position). 4α-&cetoxy-2α-bensoyloxy-5ß, 2 0-epoxy-lß-hydroxy-9,10-dioxo-7ß-trif luoromethanesulphonyloxy-ll-taxen-13α-yl (2R,3S)-3-tert-butoxycarbonylamino-3-phenyl-2-triethylsilyloxypropionate may be prepared in the following manner; 1.91 g of pyridinium chlorochromate are rapidly added to a suspension of 1.87 g of 4α-acetoxy-2α-benzoyloxy-5ß,2Q-epoxy-lß,10ß-dihydroxy-9-oxo-77ß-trifluoromethanesulphonyloxy-ll-taxen-13α-yl (2R,3S)-3-tert-butoxycarbonylamino-3-phenyl-2-triethylsilyl-oxypropionate and 4 g of activated 4 A molecular sieve in 10 cm3 of anhydrous dichloromethane maintained under an argon atmosphere at a temperature! in the region of 20°C. The reaction mixture is stirred for 20 hours at a 1 temperature in the region of 2 0°C and then purified directly by applying to a chromatography column at atmospheric pressure containing 2 00 g of silica (0.063-0.2 mm; column 3.5 dm in diameter), eluting with dichloromethane alone and then with a methanol/ dichloromethane (0.5-99.5 by volume) mixture, collecting 15-cm3 fractions. The fractions containing OTYI-J tfce desired product are pooled and eots.een.tr at ed to dryness under reduced pressure (2.7 kPa) at 40°C for 2 hours. 1.16 g of 4α-acetexy-2α-benzoyl©xy-5j3, 2 0-epoxy-l7ß-hydroxy-9,10-dioxc?-77ß-tr if luoromethane-sulphonyloxy-ll-taxen-l3a-yl (2R, 3S)-3~tert-butoxy-carbonylamino-3-pheny1-2-triethyIsilyloxypropionate are thereby obtained in the form of a pale yellow foam, the characteristics of which are as follows: - *H NMR spectrum (400 MHz; CDC13; 5 in ppm; coupling constants J in Hz) : 0.42 (flit, 6H: CH2 from triethylsilyl at position 2'); 0.81 (t, J = 7.5, 9H: CH3 from triethylsilyl at position 2'); 1.26 (s, 3H: CH3) ; 1.35 (s, 3H: CH3) ; 1.37 (s, 9H: C(CH3)3); 1.93 {s, 3H: CH3) ; 2.01 (s, 3Hs CH3) ; 2.23 and 2.43 (2 dd, J = 15 and 9, 1H each: CH2 at position 14); 2.36 and 2.89 (2 mt, 1H each: CH2 at position 6); 2.57 (s, 3H: COCH3) ; 3.82 (d, J = 7, 1H: H at position 3); 4.23 and 4.42 (2d, J = 8.5, 1H each: CH2 at position 20); 4.58 (broad s, IK: H at position 2'), 4.95 (broad d, J = 9.5, 1H: H at position 5); 5.28 (dd, J = 10 and 7-5, 1H: H at position 7); S.3.0 broa.d d, 3 - Ifc, 1H at position. 3,' S. S2 , J = 10, 1H: CONH); 5.87 (d, J = 7, 1H: H at position 2); 6.28 (broad t, J = 9, 1H; H at position 13); from 7.25 to 7.45 (mt, 5H; aromatic H at position 3'); 7.55 (t, J = 7.5,-2H: 0C0C6Hs H at the meta position); 7.67 (t, J = 7.5, 1H: OCOC6H5 H at the para position); 8.13 (d, J = 7.5 Hz, 2Hs OCOC6H5 H at the ortho position). 4α Acetoxy-2α-benzoyloxy-5ß,20-epoxy-lß, 10ß-dihydroxy-9-oxo-7/3-trifruoromethanesulphonyloxy-11-taxen-l3a-yl (2R, 3S) -3-tert-butoxycarbonylamino-3-phenyl-2-triethylsilyloxypropionate may be prepared in the following manners A solution of 3.2 cm3 of trifluoromethanesulphonic anhydride in 3 cm3 of anhydrous dichloromethane is added dropwise to a suspension of 8.85 g of 4α-acetoxy-2α-benzoyloxy-5ß? 20-epoxy-1ß,7ß, 10ß-trihydroxy-S-oxo-Xl-taxen-13α-yl (2R,3S)-3-tert-butoxycarbonylamino-3-phenyl-2-triethylsilyloxypropionate and 2 g of activated 4 A molecular sieve in 50 cm3 of anhydrous dichloromethane and 3.9 cm3 of anhydrous pyridine maintained under an argon atmosphere at a temperature in the region of -30°C. The reaction mixture is stirred for 5 minutes at -35°C and then for 1 hour at a temperature in the region of 0°C. After cooling to a temperature in the region of -10°C, 6 cm3 of distilled water are added. After filtration through a sintered glass lined with Celite, rinsing of the sintered glass with 20 cm3 of an ethyl acetate/dichloromethane (50-50 by volume) mixture and decantation, the organic phase is washed with twice 10 cm3 of distilled water, dried over magnesium sulphate, filtered through sintered glass and concentrated under reduced pressure (2.7 kPa) at a temperature in the region of 40°C. 11.3 g of an orange-coloured foam are thereby obtained, which product is purified by chromatography at atmospheric pressure on 800 g of silica (0.063-0.2 mm) contained in a column 7 cm in diameter, eluting with a methanol/ dichloromethane (1-99 and then 2-98 by volume) mixture, collecting 60-cm3 fractions. The fractions containing only the desired product are pooled and concentrated to dryness under reduced pressure (2.7 kPa) at 40°C for 2 hours. 9.55 g of 4α~acetoxy-2α-benzoyloxy-5ß,2 0-epoxy-1ß, l0ß-dihydroxy-9-oxo-7ß-trif luoromethanesulphonyloxy-ll-taxen-13a-yl (2R,3S)-3-tert-butoxycarbonylamino-3-phenyl-2-triethylsilyloxypropionate are thereby obtained in the form of a mixture. This mixture is purified by chromatography at atmospheric pressure on 700 g of silica (0.063-0.2 mm) contained in a column 6 cm in diameter, eluting with dichloromethane alone and then with an ethyl acetate/dichloromethane (5-95 by volume) mixture, collecting 60-cm3 fractions. The fractions containing only the desired product are pooled and concentrated to dryness under reduced pressure (0.27 kPa) at 40°C for 2 hours. 4.09 g of 4α-acetoxy-2α-benzoyloxy-5ß, 2 0-epoxy-l7ß, lOß-dihydroxy-9-oxo-7ß-trifluoromethanesulphonyloxy-ll-taxen-l3α-yl (2R,3S)-3-tert-butoxycarbonylamino-3-phenyl-2-triethylsilyloxypropionate are thereby obtained in the form of a pale yellow foam/ the characteristics of which are as follows: - *H NMR spectrum (300 MHz; CDC13; S in ppm; coupling constants J in Hz)% 0.38 (mt, 6H: CH2 of the triethylsilyl at position 2'); 0.79 (t, J = 7.5, 9 H: CH3 of the triethylsilyl at position 2'); 1.14 (s, 3H: CH3) ; 1.28 (s, 3HS CH3) ; 1.38 (s, 9H: C(CH3)3); 1.74 (s, IHs OH at position 1); 1.94 (s, 3H: CH3) ; 1.98 (s, 3Hs CH3) ; 2.2 0 and 2.37 (2 dd, J = 16 and 9, 1H each: CH2 at position 14); from 2.25 to 2.40 and 2.84 (2 mt, 1H each: CH2 at position 6); 2.55 {s, 3Hs C0CH3) ; 4.02 (broad s, 1H: OH at position 10); 4.04 (d, J = 7 Hs, 1H: H at position 3); 4.2 4 and 4.38 (2d, J = 8.5, 1H each: CH2 at position 20); 4.54 (broad s, 1H: H at position 2'); 4.96 (broad d, J - 9.5, 1H: H at position 5); 5.28 (broad d, J = 10, 1H: H at position 3'); 5.38 (broad s, 1H: H at position 10); 5.44 (dd, J = 10 and 7.5, 1H: H at position 7); 5.52 (d, J = 10, IHs CONH); 5.74 (d, J = 7, 1H: H at position 2); 6.34 (broad t, J = 9, 1H: H at position 13); from 7.25 to 7.40 (mt, 5H: aromatic H at position 3'); 7.50 (t, J = 7.5, 2H: OCOC6Hs H at the meta position); 7.63 (t, J = 7.5, 1H: OCOC6H5 H at the para position); 8.12 (d, J = 7.5, 2H: OCOC6Hs H at the ortho position) . 4α-Acetoxy-2α-benzoyloxy-510, 2 0-epoxy-lß,7ß,l0ß-trihydroxy-9-oxo-ll-taxen-l3α-yl (2R,3S)-3- tert-butoxycarbonylamino-3-phenyl-2-triethylsilyloxy-propionate may be prepared in the following manner: 8.05 cm3 of triethylsilyl chloride are added dropwise to a solution of 8.6 g of 4α-acetoxy-2α-benzoyloxy-5ß,2O-epoxy-lß,70,lOß-trihydroxy-9-oxo-ll-taxen-13α-yl (2R,3S)-3-tert-butoxycarbonylamino-3-phenyl-2-hydroxypropionate in 4 0 cm3 of anhydrous dichloromethane and 8.6 cm3 of anhydrous pyridine at a temperature in the region of 2 0°C under an inert argon atmosphere. The reaction mixture is stirred at a temperature in the region of 2 0°C for 2 hours and then 300 cm3 of dichloromethane are added. The organic phase is washed with twice 50 cm3 of distilled water, 50 cm3 of a 0.1N aqueous hydrochloric acid solution, 50 cm3 of distilled water, and then 50 cm3 of a saturated aqueous sodium chloride solution, dried over magnesium sulphate, filtered through sintered glass and concentrated under reduced pressure (2.7 kPa) at a temperature in the region of 4 0°C. 14.2 g of a white foam are thereby obtained, which product is purified by chromatography at atmospheric pressure on 8 00 g of silica (0.063-0.2 mm) contained in a column 7 cm in diameter, eluting with a methanol/dichloromethane (2-98 by volume) mixture, collecting 30-cm3 fractions. The fractions containing only the desired product are pooled and concentrated to dryness under reduced pressure (2.7 kPa) at 4 0°C for 2 hours. 8.8 5 g of 4α-acetoxy-2α-benzoyloxy-5ß, 2 0-epoxy-lß, 7/3,10ß-trihydroxy- 9-oxo-ll-taxen-l3α-yl (2R,3S)-3-tert-butoxy-carbonylamino-3-phenyl-2-triethylsilyloxypropionate are thereby obtained in the form of a white foam. EXAMPLE 2 0.0125 cm3 of acetic anhydride and then 13.5 mg of N,N'-dimethylamino-4-pyridine are added to a solution of 2 00 mg of 4α-acetoxy~2α-benzoyloxy-5ß,2 0-epoxy-lß, 10/?-dihydroxy-7a, 9a-epoxy-Xl-taxen-l3a-yl (2R,3S)-3-tert-butoxycarfoonylamino-3-phenyl-2-triethylsilyloxypropionate in 2 cm3 of anhydrous pyridine maintained under an argon atmosphere at a temperature in the region of 2 0°c After 3 0 minutes at a temperature in the region of 20°C, the reaction mixture is diluted with 4 0 cm3 of ethyl acetate. The organic phase is washed with twice 6 cm3 of distilled water and then 6 cm3 of a saturated aqueous sodium chloride solution, dried over magnesium sulphate,, filtered through sintered glass and concentrated under reduced pressure (2.7 kPa) at a temperature in the region of 40°C. 237.4 mg of a pale yellow foam are thereby obtained, which product is purified by chromatography at atmospheric pressure on 2 0 g of silica (0.063-0.2 mm) contained in a column 2.5 cm in diameter, eluting with an ethyl acetate/dichloromethane (elution gradient from 2-98 to 10-90 by volume) mixture, collecting 10-cm3 fractions.' The fractions containing only the desired product are pooled and concentrated to dryness under reduced pressure (2.7 kPa) at 40°C for 2 hours. 184.8 mg of 4α,10(3-diacetoxy-2α-benzoyloxy-5ß,2 0-epoxy-lß-hydroxy-7α/9α-epoxy-ll-taxen-13a-yl (2R,3S)-3-tert-butoxycarbonylamino-3-phenyl-2-triethylsilyloxy-propionate are thereby obtained in the form of a white foam, the characteristics of which are as follows; - 'H NMR spectrum (400 MHz; CDC13; S in ppm; coupling constants J in Hz); 0.34 and 0.40 (2 mt, 6Hs CH2 of the triethylsilyl at position 2'); 0.76 (t, J = 7.5, 9 H: CH3 of the triethylsilyl at position 2-'); 1.26 (s, 3H; CH3) ; 1.28 (s, 3H: CH3) ; 1.38 (s, 9Hs C(CH3)3); 1.72 (s, 3Hs CH3) ; 1.88 (s, 1H; OH at position 1); 2.01 (s, 3Hs GH3) ; 2.14 (s, 3Hs C0CH3) ; 2.23 and from 2.30 to 2.45 (dd and mt respectively, J = 15 and 9, 1H each: CH, at position 14); 2.39 (mt, 2H: CH2 at position 6); 2.48 (s, 3H: COCH3) : 4.05 and 4.30 (2 d, J = 7.5, 1H each: CH2 at position 20); 4.13 (d, J = 6, 1H: H at position 3); 4.62 (broad s, 1H: H at position 2'); 4.80 (t, J = 7.5, 1H: H at position 7); 4.88 (d, J = 6, 1H: H at position 9); 4.98 (broad s, 1H: H at position 5); 5.34 (broad d, J = 10, 1H; H at position 3'); 5.54 (d, J = 10, 1H: CONH); 5.71 (d, J = 6, 1H: H at position 10); 5.83 (d, J = 6, 1H; H at position 2); 6.10 (broad t, J = 9, 1H: H at position 13); from 7.25 to 7.45 (mt, 5H; aromatic H at position 3'); 7.48 (t, J = 7.5, 2H: OCOC6Hs H at the meta position); 7.62 (t, J = 7.5, 1H: ococ6Hs H at the para position); 8.15 (d, J = 7.5, 2H: OCOC6H5 H at the ortho position). 0.93 cm3 of a hydrofluoric acid/triethylamine (3HP/Et3N) complex is added dropwise to a solution of 180 mg of 4α, l0ß-diacetoxy-2α-benzoyloxy-5ß, 20-epoxy-l1ß-hydroxy-7α, 9α-epoxy-ll-taxen-13α-yl (2R, 3S) -3-tert-butoxycarbonylamino-3-phenyl-2-triethylsilyloxy-propionate in 1 cm3 of anhydrous dichloromethane maintained under an argon atmosphere at a temperature in the region of 2 0°C. After 7.5 hours at a temperature in the region of 20°C, the reaction mixture is diluted with 3 0 cm3 of ethyl acetate and 8 cm3 of a saturated aqueous sodium hydrogen carbonate solution. After decantation, the organic phase is washed with twice 8 cm3 of distilled water and then 8 cm3 of a saturated aqueous sodium chloride solution, dried over magnesium sulphate, filtered through sintered glass and concentrated under reduced pressure (2.7 kPa) at a temperature in the region of 4 0°C. 167.5 mg of a white foam are thereby obtained, which product is purified by preparative thin-layer chromatography on silica [9 Merck preparative silica gel 6 0F254 plates; 20 x 20 cm; thickness 0.5 mm; application in solution in dichloromethane], eluting with a methanol/ dichloromethane (4-96 by volume) mixture. After elution of the zone corresponding to the desired product with a methanol/dichloromethane (15-85 by volume) mixture, filtration through sintered glass arid then evaporation of the solvents under reduced pressure (2.7 kPa) at a temperature in the region of 40°C, 143.6 mg of 4α, 10ß-diacetoxy-2α-benzoyloxy-5ß,20--epoxy--lß-hydrQxy-7α,9α-epoxy-ll-taxen-13α-yl (2R,3S)-3-tert-butoxycarbonylamino-3-phenyl-2--hydroxypropionate are obtained in the form of a white foam, the characteristics of which are as follows: - *H NMR spectrum (4 00 MHz; CDC13; S in ppm; coupling constants J in Hz) s 1.24 ([lacuna]: CH3) ; 1.32 (s, 3H: CH3) ; 1.41 (s, 9Hs C(CH3)3); 1.68 (s, 3Hs CH3) ; 1.91 (s, IHs OH at position 1); 1.92 (s, 3Et CH3) ; 2.12 (s, 3H: COCH3) ; 2.21 and from 2.25 to 2.55 (dd and mt respectively,, J = 15 and 8, 1H each: CH, at position 14); from 2.25 to 2.55 (mt, 2El CH2 6); 2.31 (s, 3H: COCH3) ; 3.43 (wires. comp«, 1H: OH at position 2'); 4.03 and 4.30 (2d, J = 8, 1 H each: CH, at position 20); 4.13 (d, J = 6, IHs H at position 3); 4.65 (mt, 1H: H at position 2/); 4.82 (dd, J = 8.5 and 5.5, 1H: H at position 7); 4.86 (d, J = 6, IHs H at position 9); 4.93 (broad s, 1H: H at position 5); 5.34 (broad d, J = 10, 1H: H at position 3'); 5.54 (d, J = 10, 1H: CONH); 5.65 (d, J = 6, 1H: H at position 10); 5.83 (d, J = 6, 1H: H at position 2); 6.03 (broad t, J = 8, 1H: H at position 13); 7.30 (t, J = 7.5, 1H: H at the para position of the aromatic at position 3'); 7.38 (t, J = 7.5, 2H: H at the meta position of the aromatic at position 3'); 7.43 (d, J = 7.5, 2Hs H at the ortho position of the aromatic at position 3'); 7.50 (t, J1 = 7.5, 2H: OCOC6Hs H at the meta position); 7.62 (t, J = 7.5, 1H: OCOC6Hs H at the para position); 8.13 (d, J = 7.5, 2Hs OCOC6Hs H at the ortho position). EXAMPLE 3 0.805 cm3 of hydrofluoric acid/triethylamine (3HF/Et3N) complex is added dropwise to a solution of 149 mg of 4α-acetoxy-2α-benzoyloxy-5ß,2 0-epoxy-lß-hydroxy-7α, l0a-epoxy-9-oxo-ll-taxen-l3α-yl (2R,3S) -3-tert-butoxycarbonylamino-3-phenyl-2- triethylsilyloxypropionate, obtained in Example 1, in 1.5 cm3 of anhydrous dichloromethane, maintained under an argon atmosphere at a temperature in the region of 2 0°C. After 1 hour at a temperature in the region of 20°C, the reaction mixture is diluted with 50 cm3 of dichloromethane, 5 cm3 of a saturated aqueous sodium hydrogen carbonate solution and 5 cm3 of distilled water. After decantation, the organic phase is washed with 3 times 8 cm3 of distilled water and then 8 cm3 of a saturated aqueous sodium chloride solution, dried over magnesium sulphate, filtered through sintered glass and concentrated under reduced pressure (2.7 kPa) at a temperature in the region of 40°C. 13 3.2 mg of a pale yellow foam are thereby obtained, which product is purified by preparative thin-layer chromatography on silica [10 Merck preparative silica gel 60F254 plates; 20 x 20 cm; thickness 0.5 mm; application in solution in dichloromethane), eluting with a methanol/ dichloromethane (5-95 by volume) mixture. After elution of the zone corresponding to the desired product with a methanol/dichloromethane (15-85 by volume) mixture, filtration through sintered glass and then evaporation of the solvents under reduced pressure (2.7 kPa) at a temperature in the region of 40"C, 114.2 mg of 4α-acetoxy-2α-benzoyloxy-5ß,2 0-epoxy-lß-hydroxy-7o:, 10a-epoxy-9-oxo-ll-taxen-13α-yl (2R, 3S)-3-tert-butoxycarbonylamino-3-phenyl-2-hydroxypropionate are obtained in the form of a white foam, which product is purified by preparative thin-layer chromatography on silica [8 Merck preparative silica gel 60F254 plates; 20 x 20 cm; thickness 0.5 mm; application in solution in dichloromethane], eluting with a methanol/dichloromethane (2-98 by volume) mixture. After elution of the zone corresponding to the desired product with a methanol/dichloromethane (15-85 by volume) mixture, filtration through sintered glass and then evaporation of the solvents under reduced pressure (2.7 kPa) at a temperature in the region of 40°C, 92.8 mg of 4α-acetoxy-2α-benzoyloxy-5j3,2 0-epoxy~lj3-hydroxy-7α,10a-epoxy-9-oxo-ll-taxen-l3a-yl (2R,3S)-3-tert-butoxycarbonylamino-3-phenyl-2-hydroxypropionate are obtained in the form of a white foam, the characteristics of which are as follows; - 'H NMR spectrum (4 00 MHz; CDC13; at a temperature of 333°K, S in ppm; coupling constants J in Hz): 1.23 (s, 3H: CH,) ; 1.33 (s, 3H: CH3) ; 1.41 (s,! 9H: C(CH3)3); 1.78 (s, 3H: CH3) ; 1.83 (s, 3H: CH3) ; 1.88 (s, 1H: OH at position 1); 2.12 and 2.35 (2 dd, J = 15 and 8, 1H each: CH2 at position 14); 2.28 (s, 3H: COCH3) ; 2.33 and 2.43 (2 dd, H at position 7); 3.85 (unres. comp., 1H: OH at position 2'); 4.28 (limiting AB, J = 8, 2H: CH2 at position 20); 4.52 (d, J = 6.5, 1H: H at position 3); 4.63 (mt, 1H: H at position 2'); 4.83 (mt, 1H: H at position 10); 5.06 (d, J = 5, 1H: H at position 5); 5.30 (broad d, J = 10, 1H: H at position 3'); 5.53 (d, J = 10, 1H: CONH); 5.59 (d, J = 6.5, 1H: H at position 2); 6.22 (broad t, J = 8, 1H: H at position 13); 7.30 (t, J = 7.5, 1H: H at the para position of the aromatic at position 3'); 7.37 (t, J = 7.5, 2H: H at the meta position of the aromatic at position 3'); 7.44 (d, J = 7.5, 2H: H at the ortho position of the aromatic at position 3f); 7.50 (t, J = 7.5, 2H: OCOC6Hs H at the meta position); 7.61 (t, J = 7.5, 1H: OCGC6H- H at the para position); 8.09 (d, J = 7.5, 2H: OCOC6H- H at the ortho position). EXAMPLE 4 1 mg of sodium hydride at 50 % in oil is added to a solution of 10 mg of 4α-acetoxy-2α-benzoyloxy-5/?,2 0-epoxy-lß, 10/?-dihydroxy-7α, 9α-epoxy-ll-taxen-13α-yl (2R,3S)-3-tert-butoxycarbonylamino-3-phenyl-2-triethylsilyloxypropionate in 0.1 cm3 of methyl iodide and 0.01 cm3 of anhydrous dimethylformamide under an argon atmosphere at a temperature in the region of 20°C. After 12 minutes at a temperature in the region of 20°c, the crude reaction mixture is purified by preparative thin-layer chromatography on silica [l Merck preparative silica gel 60F2S4 plate; 20X20 cm; thickness 0.5 mm; application of the crude reaction mixture], eluting with a methanol/dichloromethane (3-97 by volume) mixture. After elution of the zone corresponding to the desired product with a methanol/dichloromethane (15-85 by volume) mixture, filtration through cotton and then evaporation of the solvents under reduced pressure (2.7 kPa) at a temperature in the region of 40°C, 4.7 mg of 4α-acetoxy-2α-benzoyloxy-5j3,2 0-epoxy-lß-hydroxy-lOß-methoxy~7α,9α-epoxy-ll-taxen-l3α-yl (2R, 3S)-3-tert-butoxycarbonylamino-3-phenyl-2- triethylsilyloxypropionate are obtained in the form of a white lacquer. 0.01 cm3 of hydrofluoric acid/triethylamine (3HF/Et3N) complex is added dropwise to a solution of 4 mg of 4α-acetoxy-2α-benzoyloxy-5ß,20-epoxy-lß-hydroxy-10ß-methoxy-7α,9α-epoxy-ll-taxen-13α-yl (2R,3S)-3-tert-butoxycarbonylamino-3-phenyl-2-triethylsilyloxypropionate in 0.1 cm3 of anhydrous dichloromethane maintained under an argon atmosphere at a temperature in the region of 2 0°C. After 35 minutes at a temperature in the region of 20°c, the crude reaction mixture is purified by preparative thin-layer chromatography on silica [1 Merck preparative silica gel 60F254 plate; 2 0 x 2 0 cm; thickness 0.5 mm; application of the crude reaction mixture], eluting with a methanol/dichloromethane (4-96 by volume) mixture. After elution of the zone corresponding to the desired product with a methanol/dichloromethane (15-85 by volume) mixture, filtration through cotton and then evaporation of the solvents under reduced pressure (2.7 kPa) at a temperature in the region of 40°C, 3.3 mg of 4α-acetaxy-2α-benzoyloxy-5ß,2 0-epoxy-lj3-hydroxy-10j3-methoxy-7α, 9α-epoxy-ll-taxen-13α-yl (2R,3S)-3-tert-butaxycarbonylamino-2-hydroxy-3-phenylpropionate are obtained in the form of a white lacquer, the characteristics of which are as follows: - 1H NMR spectrum (400 MHz; CDC13; . at a temperature of 333°K, S in ppm; coupling constants J in Hz): 1=17 (s, 3H: CH3) ; 1.22 (s, 3H? CH3) ; 1.41 (s, 9H: C(CH3)3); 1.67 (s, 3Hs CH3) ; 1.94 (s, 1H: OH at position 1); 2.00 (s, 3H: CH3) ; 2.23 and 2.41 (2 dd, respectively J = 15 and 8 and J = 15 and 10, 1H each: CH2 at position 14); from 2.20 to 2.40 (mt, 2HS CH2 at position 6); 2.31 (s, 3H: COCH3) ; 3.33 (s, 3H: OCH3) ; 4.03 (unres. comp., 1H: OH at position 2'); 4.03 and 4.31 (2 d, J = 7.5, 1H each: CH2 at position 20); 4.13 (d, J = 6.5, 1H: H at position 3); 4.29 (d, J = 7, 1H: H at position 9); 4.67 (mt, 1H: H at position 2'); 4.77 (dd, J = 8.5 and 5.5, 1H: H at position 7); 4.90 (d, J = 7, 1H: H at position 10); 4.93 (broad s, 1H: H 5); 5.37 (broad d, J = 10, 1H: H at position 3'),* 5.61 (d, J = 10, 1 JH: CONH) ; 5.81 (d, J = 6.5, 1H; H at position 2); 6.06 (mt, 1H: H at position 13)| 7.30 (t, J = 7.5, 1H; H at the para position of the aromatic at position 3'); 7.38 (t, J = 7.5, 2H: H at the meta position of the aromatic at position 3'); 7.46 (d, J = 7.5, 2H: H at the ortho position of the aromatic at position 3'); 7.49 (t, J = 7.5, 2H: OCOC6Hs H at the meta position); 7.63 (t, J = 7.5, 1H: OCOC6H5 H at the para position); 8.13 (d, J = 7.5, 2H: OCOC6H5 H at the ortho position) . EXAMPLE 5 4α-Acetoxy-2α-ben2oyloxy-5ß,2 0-epoxy-lß-hydroxy-7α,9α-oxa-10ß-propanoyloxy-ll-taxen-13α-yl (2R,3S)-3-tert-butoxycarbonylamino-3-phenyl~2-hydroxypropionate may be prepared in the following manner: 0.0053 cm3 of concentrated hydrochloric acid (36 %, d = 1.18) is added to a solution of 50 mg of 4α-acetoxy-2α-benzoyloxy-5j3,2 0-epoxy-lß-hydroxy»7α,9α-oxa-10ß-prapanoyloxy-ll-taxen-13α-yl (2R, 4S, 5R) -3-tert-butoxycarbonylamino-2--(4-methoxyphenyl) -4-phenyl-l,3-oxazolidine-5-carboxylate in 0.5 cm3 of ethyl acetate maintained at a temperature in the region of 20°C. After 2 hours at a temperature in the region of 2 0°C, the crude reaction mixture is purified by preparative thin-layer chromatography: 1 Merck preparative silica gel 60F2S4 plate, 20 x 20 cm, thickness 1 mm, eluting with a methanol/dichloromethane (5-95 by volume) mixture. After elution of the zone corresponding to the desired product with a methanol/dichloromethane (15-85 by volume) mixture, filtration through sintered glass and then evaporation of the solvents under reduced pressure (2.7 kPa) at a temperature in the region of 40°C, 21 mg of 4α-acetoxy-2α-benzoyloxy-5ß,2 0-epoxy-lß-hydroxy-7α,9α-oxa-l0ß-propanoyloxy-ll-taxen-l3a-yl (2R,3S)-3-tert-butoxycarbonylamino-3-phenyl~2-hydroxypropionate are obtained in the form of a white foam, the characteristics of which are as follows: - *H NMR spectrum (400 MHz; CDC13; 5 in ppm) : i.ie (t, J = 7.5 Hz, 3Hs CH3 of the ethyl); 1.26 (s, 3H: CH3) ; 1.33 (s, 3H: CH3) ; 1.41 (s, 9Hs C(CH3)3); 1.69 (s, 3H: CH3) ; 1.92 (s, 3H; CH3) ; 2.23 and from 2.25 to 2.50 (dd and mt respectively, J'= 16 and 8 Hz, 1H each: CH2 14); from 2.25 to 2.50 (mt, 4H; CH, 6 and OCOCH, ethyl); 2.33 (s, 3H: COCH3) ; 3.97 (broad s, 1H: OH at position 2l) ; 4.03 and 4.31 (2d, J = 8 Hz, 1H each? CH22G); 4.13 (d, J = 6 Hz, IHs H 3); 4.68 (mt, 1H: H 2l)°, 4.84 (dd, J = 8.5 and 5.5 Hz, 1H: H 7); 4.88 (d, J = 6 Hz, IHs H 9); 4.96 (broad s, 1H: H 5); 5.35 (broad d, J = 10 Hz, 1H: H 3'); 5.58 (d, J = 10 HZ, 1H:. CONH) ; 5.69 and 5.85 (2 d, J = 6 Hz, 1H each: H 2 and H 10); 6.05 (broad t, J = 8 Hz, 1H: H 13); 7.31 (t, J = 7.5 Hz, IHs H at the para position of the aromatic at position 3'); 7.39 (t, J = 7.5 Hz, 2Hs H at the meta position of the aromatic at position 3'); 7.46 (d, J = 7.5 Hz, 2H: H at the ortho position of the aromatic at position3'); 7.50 (t, J = 7.5 HZ, 2H? OCOC6Hs H meta); 7.53 (t, J = 7.5 Hz, 1H: OCOC6H5 H para); 8.13 (d, J = 7.5 Hz, 2H: OCOC6H5 H ortho). 4α-Acetoxy-2α-benzoyloxy-5ß,2 o-epoxy-1ß-hydroxy-7α,9α-oxa-10ß-propanoyloxy-ll-taxen-13α:-yl (2R,4S,5R)-3-tert-butoxycarbonylamino-2-(4-methoxyphenyl)-4-phenyl-l,3-oxazolidine-5-carboxylate may be prepared in the following manners 20 mg of 4(N,N-dimethylamino)pyridine and then 0.042 cm3 of propionic anhydride are added successively to a solution of 100 mg of 4α-acetoxy-2α-ben2oyloxy-5£,2 0-epoxy-l/^i0ß-aihydroxy-7α,9Q:-Qxa-ii-taxen-13α-yl (2R,4S*5R)-3-tert-butoxycarbonylamino-2-C4-methoxyphenyl)-4-phenyl-l,3»©xazolidine~5-carboxylate in 1 cm3 of anhydrous pyridine maintained under an argon atmosphere at a temperature in the region of 20°C, After 2 hours at a temperature in the region of zo°C, the reaction mixture is diluted with 5 cm3 of dichloromethane and 2 cm3 of distilled water. After decantation, the organic phase is dried over magnesium sulphate, filtered through sintered glass and concentrated under reduced pressure (2.7 kPa) at a temperature in the region of 40°C. A colourless oil is thereby obtained which is purified by preparative thin-layer chromatography: 3 Merck preparative silica gel 60F254 plates, 20X20 cm, thickness 1 mm, application in solution in a minimum volume of dichloromethane, eluting with a methanol/dichloromethane (5-95 by volume) mixture. After elution of the zone corresponding to the desired compound with a methanol/ dichloromethane (15-85 by volume) mixture, filtration through sintered glass and then evaporation of the solvents under reduced pressure (2.7 kPa) at a temperature in the region of 4 0°C, 51 mg of 4or-acetoxy-2α-benzoyloxy-5ß,20-epoxy-lß-hydroxy-7α!,9α:-oxa-l0ß-propanoyloxy-ll-taxen-13α-yl (2R,4S,5R)-3-tert-butoxycarbonylamino-2-(4-methoxyphenyl)-4-phenyl-l# 3-oxazolidine-5-carboxylate are obtained in the form of a white foam,, the characteristics of which are as follows: - *H NMR spectrum (400 MHz; CDC13; 6 in ppm) : 1.04 (t, J = 7.5 Hz, 3H: CH3 of the ethyl); 1.05 (s, 9K: C(CH3)3); 1.24 (s, 6H: CH3) ; 1.63 (s, 3Hs CH3) ; 1.70 (s, 3H: CH3) ; 1.80 (s, 3Hs COCH3) ; 2.10 and from 2.15 to 2.55 (dd and mt respectively, J = 16 and 8 Hz, 1H each: CH2 14); from 2.15 to 2.55 (mt, 4H: CH2 6 and OCOCH2 ethyl); 3.80 (s, 3Hs ArOCH3) ; 3.92 and 4.22 (2d, J = 8 Hz, 1H each: CH2 20); 4.02 (d, J = 6 HZ, 1H: H 3); 4.62 (d, J = 5 Hz, lHs H 2'); 4.73 (dd, J = 8 and 7.5 Hz, 1H: H 7); 4.78 (d, J = 6 Hz, 1H: H 9); 4.88 (broad s, 1H: H 5); 5.35 (broad d, J = 5 Hz, 1H: H 3'}; 5.63 and 5.75 (2 d, J = 6 Hz, 1H each: H 2 and H 10); 5.93 (broad t, J = 8 Hz, 1H: H 13); 6.30 (broad s, 1H: H 5'); 6.89 (d, J = 8.5 Hz, 2Hs aromatic H at the ortho position of the OCH3) ; from 7.25 to 7.50 (mt, 9H: aromatic H at position 3' -aromatic H at the meta position of the OCH3 and OCOC6Hs H meta); 7.58 (t, J = 7.5 Hz, 1H: OCOC6H5 H para); 8.03 (d, J = 7.5 Hz, 2H: OCOC6 H5 ortho) . 4α-Acetoxy-2α-benzoyloxy-5ß,2 0-epoxy-lß, 10ß-dihydroxy-7α,9α-oxa-ll-taxen-13α-yl (2R,4S,5R)-3-tert-butoxycarbonylamino-2-(4-methoxypheny1)-4-phenyl-1,3-oxazolidine-5-carboxylate may be prepared in the following manner: 60 mg of sodium borohydride are added to a solution of l.l g of 4α-acetoxy-2α-benzoyloxy-5ß,2 0-epoxy-lß~hydroxy-9 , lQ-dioxo-7ß-trif luoromethane-sulphonate-ll-taxen-13α-yl (2R, 4S,5R)-3-tert-butoxycarbanylamino-2-(4-methoxyphenyl)-4-phenyl-i,3-oxazolidine-5-carboxylate in 30 cm3 of absolute ethanol maintained under an argon atmosphere at a temperature in the region of 0°c. After one hour at a temperature in the region of 0°C, the reaction mixture is diluted with 10 0 cm3 of ethyl acetate. The organic phase is washed with 50 cm3 of distilled water and then twice 25 cm3 of a saturated aqueous sodium chloride solution,, dried over magnesium sulphate,, filtered through sintered glass and concentrated under reduced pressure (2.7 kPa) at a temperature in the region of 4 0"C, 1.04 g of a pale yellow foam is thereby obtained, which product is purified by chromatography at atmospheric pressure on 50 g of silica (0.063-0.2 mm) contained in a column 2.5 cm in diameter, eluting with a methanol/ dichloromethane (2-98 by volume) mixture, collecting 2 0-cm3 fractions. The fractions containing only the desired product are pooled and concentrated to dryness under reduced pressure (2.7 kPa) at 4 0°C for 2 hours. 230 mg of 4α-acetoxy-2α-benzoyloxy--5|3/2O-epoxy-10,lOß-dihydroxy-7α,9α-oxa-ll-taxen-13α-yl (2R,4S,5R)-3-tert-butoxycarbonylamino-2-(4-methoxyphenyl)-4-phenyl-l,3-oxazolidine-5-carboxylate are thereby obtained in the form of a white foam, the characteristics of which are as follows: - *H NMR spectrum (400 MHz; CDC13; 6 in ppm) : 1.05 (s, 9H: C(CH3)3); 1.10 (s, 3H; CH3) ; 1.25 (s, 3H: CH3) ; 1.58 (s, 3H: CH3) ; 1.70 (s, 3H: CH3) ; 1.85 (broad s, 3Hs C0CH3) ; 2.10 and 2.22 (2 dd, J = 16 and 8 Hz, 1H each: GH2 14); from 2.25 to 2.45 (mt, 2H: CH2 6); 3.82 (s, 3Hs ArOCH3) ; 3.93 and 4.23 (2d, J = 8 Hz, 1H each? CH2 20); 4.08 (d, J = 6 Hz, 1H: H 3); 4.62 (d, J = 5 Hz, 1H: H 2')', from 4.70 to 4.80 (mt, 2Hs H 9 and H 10); 4.80 (dd, J = 8.5 and 6 Hz, 1H: H 7); 4.88 (broad s, 1H: H5); 5.36 (unres. comp., 1H: H 3'); 5.75 (d, J = 6 Hz, 1H: H 2); 6.02 (broad t, J = 8 Hz, 1H: H 13); 6.37 (broad unres. comp., 1H: H 5'); 6.95 (d, J = 8.5 Hz, 2H: aromatic H at the ortho position of the OCH3) ; from 7.25 to 7.55 (mt, 9H; aromatic H at position 3' -aromatic H at the meta position of the OGH3 and OCOC6H5 H meta); 7.65 (t, J = 7.5 Hz, 1H: OCOC6H5 H para) [lacuna]7 (d, J = 7.5 Hz, 2Hs OCOC6H5 H ortho). 4α-Acetoxy-2α-benzoyloxy-5ß,2 0-epoxy-lj3-hydroxy-9, lO-dioxo-7ß-trif luoromethanesulphonate-ll-taxen-13α-yl (2R,4S,5R)-3-tert-butoxycarbonylamino-2-(4-methoxyphenyl)-4-phenyl-l,3-oxazolidine-5- carboxylate may be prepared in the following manner: 1.8 g of pyridinium chlorochromate are rapidly added to a suspension of 2.2 g of 4α-acetoxy-2α-benzoyloxy-50,2O-epoxy-lß, l0ß-dihydroxy-9-oxo-7ß-trifluoromethanesulphonate-ll-taxen-13α-yl (2R,4S,5R)-3-tert-butoxycarbonylamino-2-(4-methoxyphenyl)-4-phenyl-l,3-oxazolidine-5-carboxylate and 4.5 g of activated 4 A molecular sieve in 10 cm3 of anhydrous dichloromethane maintained under an argon atmosphere at a temperature in the region of 20°C, The reaction mixture is stirred for 17 hours at a temperature in the region of 2Q°c and then filtered through clarcel. The solid residue is rinsed with dichloromethane and then the filtrate is concentrated under reduced pressure (2.7 kPa) at a temperature in the region of 40°C, A brown foam is thereby obtained which is purified by chromatography at atmospheric pressure on 2 00 g of silica (0.063-0.2 mm) contained in a column 4 cm in diameter, eluting with a methanol/dichloromethane (0.5-99.5 by volume) mixture, collecting 2 0-cm3 fractions. The fractions containing only the desired product are pooled and concentrated to dryness under reduced pressure (2.7 kPa) at 4C°C for 2 h. 1.5 g of 4α-acetoxy-2α-benzoyloxy~5j3,2 0-epoxy-lß-hydroxy-9,10-dioxo-7ß-trifluoromethanesulphonate-ll-taxen-13α-yl (2R,4S,5R)-3-tert-butoxycarbonylamino-2-(4-methoxyphenyl) -4-phenyl-l, 3-oxazolidine-5-ciarboxylate are thereby obtained in the form of a yellow foam, the characteristics of which are as follows: - 'H NMR spectrum (400 MHz; CDC13; S in ppm) : 1.07 (s, 9H: C(CH3)3)? 1.20 (s, 3HJ CH3) ; 1.27 (s, 3H: CH3) ; 1.58 (s, 3H: CH3) ; 1.85 (s, 3H: CH3) ; 1.94 (unres. comp., 3H: COCH3) ; 2.13 and 2.27 (2 dd, J = 16 and 8 Hz, 1H each: CH2 14); 2.13 and 2.82 (2 mts, 1H each: CH2 6); 366 (d, J = 6.5 Hz, 1H: H 3); 3.84 (s, 3H: ArOCH3) ; 4.11 and 4.31 (2d, J = 8 Hz, 1H each: CH2 20); 4.58 (d, J = 5 Hz, 1H: H 2'); 4.81 (broad d, J = 10 Hz, 1H: H 5); 5.18 (dd, J = 10 and 7.5 Hz, 1H: H 7); 5.44 (unres. comp., 1H: H 3'); 5.77 (d, J = 6.5 Hz, 1H: H 2); 6.11 (broad t, J = 8 Hz, 1H: H 13); 6.40 (unres. comp., 1H: H 5'); 6.91 (d, J = 8.5 Hz, 2H: aromatic H at the ortho position of the OCH3) ; from 7.30 to 7.50 (mt, 7H: aromatic H at position 3' - aromatic H at the meta position of the OCH3) ; 7.51 (t, J = 7.5 Hz, 2H: OCOC6H5 H meta); 7.66 (t, J = 7.5 Hz, 1H: OCOC6Hs H para); 8.02 (d, J = 7.5 Hz, 2H: OCOC6Hs H ortho). The preparation of 4α-acetoxy-2α-benzoyloxy-5ß,2 0-epoxy-lß,10ß-dihydroxy-9-oxo-7|3-trif luoromethane-sulphonate-ll-taxen-13α-yl (2R, 4S, 5R)-3-tert-butoxycarbonylamino-2-(4-methoxypheny1)-4-phenyl-1,3-oxazolidine-5-carboxylate may be carried out, for example, according to the procedure described in Patent FR 9,408,198 (first filing of 04/07/94). EXAMPLE 6 4α-Acetoxy-2α-benzoyloxy-5ß, 2 0-epoxy-lß- hydroxy-10ß-methoxyacetoxy-'7α,9α-oxa-ll-taxen-13α-yl (2R, 3S) -3 -tert-butoxycarboixylamino-3 -pheny 1-2 -hydroxypropionate may be prepared in the following manner: 0.0053 cm3 of concentrated hydrochloric acid (36 %, d = 1.18) is added X-o a solution of 3 0 mg of 4α-acetoxy-2α-benzoyloxy-5ß, 2 0-epoxy-lß-hydroxy-10ß-BiethoxyacetoxY-7α,9α-oxa-ll-taxen-13α-yl (2R, 4S , 5R} ~3-tert-butoxycarbonylamino-2-(4-methoxyphenyl)-4-phenyl-l,3-oxazolidine-5-carboxylate in 1 cm3 of ethyl acetate maintained at a temperature in the region of 2 0°C. After 45 minutes at a temperature in the region of 20°C, 0.002 cm3 of concentrated hydrochloric acid is added. After 2 hours at a temperature in the region of 20°C, the crude reaction mixture is purified by applying to preparative thin-layer chromatography: 1 Merck preparative silica gel 60F254 plate, 2 0X2 0 cm, thickness 0.5 mm, eluting with a methanol/ dichloromethane (5-95 by volume) mixture. After elution of the sone corresponding to the desired product with a methanol/dichloromethane (15-85 by volume) mixture, filtration through sintered glass and then evaporation of the solvents under reduced pressure (2.7 kPa) at a temperature in the region of 4 0°C, 13 mg of 4α-acetoxy-2α-benzoyloxy-5ß,2 0-epoxy-lß-hydroxy-10ß-methoxyacetoxy-7α,9α-oxa-ll-taxen-13α-yl (2R,3S)-3-tert-butoxycarbonylamino-3-pheny1-2-hydroxypropionate are obtained in the form of a white foam,, the characteristics of which are as follows: - 1H NMR spectrum (400 MHz; CDC13; 5 in ppm) : 1.24 (s, 3H: CH3) ; 1.31 (s, 3Hs CH3) ; 1.40 (s, 9H: C(CH3)3); 1.67 (s, 3H: CH3) ; 1.86 (s, 3H; CH3) ; 1.99 (s, 1H: OH at position 1); 2.2 0 and from 2.2 5 to 2.5 0 (dd and mt respectively, j = 16 and 8 Hz, 1H each; CH2 14); from 2.25 to 2.50 (mt, 2H: CH2 6); 2.31 (s, 3H: C0CH3) ; 3.44 (s, 3H: OCH3) ; 3.87 (broad s, 1H: OH at position 2'); 4.01 and 4.18 (2 d, J = 8 Hz, 1H each? CH2 20); 4.04 and 4.11 (2 d, j = 16.5 Hz, 1H each: OCOCH2O) ; 4.10 (d, J = 6 Hz, 1H: H 3); 4.64 (mt, 1H: H 2s); 4.80 (dd, J = 8.5 and 5.5 Hz, 1H: H 7); 4.86 (d, J = 6 Hz, 1H: H 9); 4.92 (broad s, iHs H 5); 5.30 (broad d, J = 10 Hz, 1H: H 3'); 5.53 (d, J = 10 Hz, IHs CONH); 5.74 and 5.80 (2 d, J = 6 Hz, 1H each: H 2 and H 10); 6.01 (broad t, J = 8 Hz, 1H: H 13); 7.30 (t, J = 7.5 Hz, IHs H at the para position of the aromatic at position 3s); 7.36 (t, J = 7.5 Hz, 2Hs H at the meta position of the aromatic at position 3'); 7.42 (d, J = 7.5 Hz, 2H: H at the ortho position of the aromatic at position 3'); 7.47 (t, J = 7.5 Hz, 2Hs OCOC6Hs H meta); 7.61 (t, J = 7.5 Hz, 1H: OCOC6Hs H para); 8.11 (d, J = 7.5 Hz, 2H: OCOC6H5 H ortho). 4α-Acetoxy-2α-benzoyloxy-5ß,2 0-epoxy-lß-hydroxy-l0ß-methoxyacetoxy-7α,9α-oxa-ll-taxen-13α-yl (2R,4S,5R)-3-tert-butoxycarbonylamino-2-(4-methoxyphenyi)-4-phenyl-l,3-oxazolidine-5-carboxylate may be prepared in the following manner: 0.093 cm3 of n-butyllithium (in 1.6M solution in hexane) and then 8 minutes later 0.023 cm3 of methoxyacetyl chloride are added to a solution of 9 0 mg of 4α-acetoxy-2α-benzoyloxy-5ß/20-epoxy-lß/10/5-dihydroxy-7α,9α-oxa-ll-taxen-13α-yl (2R,4S,5R)-3-tert-butoxycarbonylamino-2-(4-methoxyphenyl)-4-phenyl-l,3-oxazolidine-5-carboxylate in 2 cm3 of anhydrous tetrahydrofuran maintained under an argon atmosphere at a temperature in the region of -78°C. The cooling bath is removed and then the crude reaction mixture, after returning t© a temperature in the region of 2 0°c# is purified by applying to preparative thin-layer chromatographys 2 Merck preparative silica gel 60F254 plates, 20X20 cm, thickness 1 mm, eluting with a methanol/dichloromethane (5-95 by volume) mixture. After elution of the zone corresponding to the desired product with methanol/dichloromethane (15-85 by volume) mixture, filtration through sintered glass and then evaporation of the solvents under reduced pressure (2.7 kPa) at a temperature in the region of 40°C, 31 mg of 4α-acet©xy~2α-bensoyloxy-5ß,2 0-epoxy-lß-hydroxy-lQj3-methoxyacetoxy-7α,9α-oxa-ll-taxen-13α-yl (2R,4S,5R)-3-tert-butoxycarbonylamino-2-(4-methoxyphenyl)-4-phenyl-1,3-oxazolidine-S-carboxylate are obtained in the form of a white foam? the characteristics of which are as follows: - 1H NMR spectrum (400 MHz; CDC13; S in ppm) : 1.05 (s, 9H: C(CH3)3); 1.26 (s, 6H: CH-,) ; 1.64 (s, 3H: CH-,) ; 1.67 (unres. comp., 3H: CH3) ; 1.78 (s, 3Hs COCH3) ; 2.10 and 2.21 (2 3d, J = 16 and 8.5 Hz, 1H each: CH2 14); 2.29 (mt, 2H: CH2 6); 3.45 (s, 3H; OGH3) ; 3.81 (s, 3Hs ArOCH3) ; 3.92 and 4.24 (2 d, J = 8 Hz, 1H each: CH2 20); 4.00 (d, J = 6 Hz, 1H: H 3); 4.03 and 4.10 (2 d, J = 16 Hz, 1H each? OCOCH20) ; 4.62 (d, J = 5 Hz, 1H: H 2"); 4.75 (dd, J = 8 and 7.5 Hz, 1H: H 7); 4.82 (d, J = 6 Hz, 1H: H 9); 4.85 (broad s, IHs H 5); 5.34 (unres. comp. 1H: H 3'); 5.68 and 5.75 (2 d, J = 6 Hz, 1H each: H 2 and H 10); 5.95 (mt, 1H: H 13); from 6.30 to 6.45 (very broad unres. comp., 1H; H Sf); 6.92 (d, J = 8.5 Hz, 2Hs aromatic H at the ortho position of the OCH3) ; from 7.25 to 7.50 (mt, 9Hs aromatic H at position 3' - aromatic H at the meta position of the oCH3 and OCOC6Hs H meta); 7.62 (t, J = 7.5 Hz, 1H: OCOC6H5 H para); 8.Q6 (d, J = 7.5 Hz, 2H; OCOC6Hs H ortho). EXAMPLE 7 4α-Acetoxy-2α-benzoyloxy-5ß,2Q-epoxy-lß-hydroxy-10ß-dimethylaminocarbonyloxy-7α,9α:-oxa-ll-taxen-13α-yl (2R,3S)-3-tert-butoxycarbonylamino-3-phenyl-2~hydroxypropionate may be prepared in the following manner; 0.0043 cm3 of concentrated hydrochloric acid (36 %, d = 1.18) is added to a solution of 40 mg of 4α-acetoxy-2α:-benzoyloxy--5ß,2 0-epoxy-lß-hydroxy-l0ß-dimethylaminocarbonyloxy-7α,9α-oxa-l^l-taxen-13α-yl (2R,4S,5R)-3-tert-butoxycarbonylamino-2-(4- methoxyphenyl)-4-phenyl-l,3-oxazolidine-5-carboxylate in 1 cma of ethyl acetate maintained at a temperature in the region of 2 0°C. After 1.5 hours at a temperature in the region of 2 0°C, the crude reaction mixture is purified by applying to preparative thin-layer chromatographys 2 Merck preparative silica gel SOP^ plates, 20X20 cm, thickness 0.5 mm, eluting with a methanol/diclvloromethane {5-9 5 by volume) mixture. After elution of the zone corresponding to the desired product with a methanol/dichloromethane (15-85 by volume) mixture, filtration through sintered glass and then evaporation of the solvents under reduced pressure (2.7 kPa) at a temperature in the region of 40°C, 20 mg of 4α-acetoxy-2α-benzoyloxy-5j3,20-epoxy-lj3-hydroxy-10j3-dimethylaminocarbonyloxy-7α, 9α-oxa-ll-taxen-13α-yl J - 6 Hz, IH: H 9); 4.9 5 (broad s, 1H: H 5); 5.2 4 (broad d, J = 10 Hz, 1H: H 3'); 5.58 (d, J = 10 Hz, IHJ CONH); 5.69 and 5.83 (2 d, J = 6 Hz, 1H each: H 2 and H 10); 6.07 (broad t, J = 8 Hz, 1H: H 13); 7.31 (t, J = 7.5 Hz, 1H: H at the para position of the aromatic at position 3'); 7.39 (t, J = 7.5 Hz, 2Hs H at the meta position of the aromatic at position 3'); 7.46 (d, J = 7.5 Hz, 2H; H at the ortho position of the aromatic at position 3'); 7.48 (t, J = 7.5 Hz, 2Hs OCOC6H5 H meta); 7.62 (t, J = 7.5 Hzf 1H: OCOC6H5 H para)? 8.13 (d, J = 7.5 HZ, 2HS dCOC6Hs H ortho). 4α-Acetoxy-2α-benzoyloxy-5ß,2 0-epoxy--lß~ hydroxy-!0|3-dimethylaminocarbonyl©xy-7α/9α-oxa-ll-taxen-13α-yl (2R,4S,5R)-3-tert-butoxycarbonylamino-2-(4-methoxyphenyl)-4-phenyl-l,3-oxazolidine-5-carboxylate may be prepared in the following manner: 0.103 cm3 of n-butyllithium (in 1.6M solution in hexane) and then 5 minutes later 0.0253 cm3 of dimethylaminocarbamoyl chloride are added to a solution of 100 mg of 4α-acetoxy-2α-benzoyloxy-5ß,2 0-epoxy-1ß,10ß-dihydroxy-7α, 9α-oxa-ll-taxen-13α-yl (2R, 4S, 5R) -3-tert-butoxycarbonylamino-2-(4-methoxyphenyl)-4-phenyl-l,3-oxazolidine~5-carboxylate in 2 cm3 of anhydrous tetrahydrofuran maintained under an argon atmosphere at a temperature in the region of -78°c. After 30 minutes at a temperature in the region of -78"C, the cooling bath is removed and then the cooled reaction mixture, after returning to a temperature in the region of 20°C, is diluted with 1 cm3 of distilled water. After decantation, the aqueous phase is reextracted with 2 cm3 of ethyl acetate. The pooled organic phases are dried over magnesium sulphate, filtered through sintered glass and concentrated under reduced pressure (2.7 kPa) at a temperature in the region of 40°C. 99 mg of a colourless lacquer are thereby obtained, which product is purified by preparative thin-layer chromatography! 2 Merck preparative silica gel 60F254 plates, 20x20 cm, thickness 1 mm, application in solution in a minimum of dichloromethane, eluting with a methanol/ dichloromethane (5-95 by volume! mixture. After elution of the zone corresponding to the desired product with methanol/dichloromethane (15-85 by volume) mixture, filtration through sintered glass and then evaporation of the solvents under reduced pressure (2.7 kPa) at a temperature in the region of 4 0 °C, 4 3 mg of 4α-acetoxy-2α-benzoyloxy-5ß/20-epoxy-lj3-hydroxy-10ß-dimethylaminocarbonyloxy-7α,9α-oxa-ll-taxen-13α-yl (2R,4S,5R)-3-tert-butoxycarbonylamino-2-(4-methoxyphenyl)~4~phenyl-l,3-oxazolidine-5-carboxylate are obtained in the form of a white foam, the characteristics of which are as follows: - 1H NMR spectrum (400 MHz; CDC13; respectively, J = 16 and 8 Hz, 1H each: CH2 14); from 2.15 to 2.35 (mt, 2H; CH2 6); 2.92 (s, 6H? N(CH3)2); 3.80 (s, 3H: ArOCH3) ; 3.92 and 4.23 (2 d, J = 8 Hz, 1H each: CH2 20); 4.02 (d, J = 6 Hz, 1H: H 3); 4.62 (d, J = 5 Hz, 1H: H 2'); 4.71 (dd, J = 8 and 7.5 Hz, 1H: H 7); 4.83 (d, J = 6 Hz, 1H: H 9); 4.88 (broad s, 1H: H 5); 5.35 (broad d, J = 5 Hz, 1H: H 3'); 5.68 and 5.77 (2 d, J = 6 Hz, 1H: H 2 and H 10); 6.00 (broad t, J = 8 Hz, 1H: H 13); 6.30 (s, 1H: H 5"); 6.92 (d, J = 8.5 Hz, 2H: aromatic H at the ortho position of the OCH3) ; from 7.25 to 7.50 (mt, 9H: aromatic H at position 3f - aromatic H at the meta position of the OGH3 and OCOCsHs H meta) ; 7.60 (t, J = 7.5 Hz, 1H: 0C0C6Hs H para); 8.05 (d, J = 7.5 Hz, 2H: OCOC6Hs H ortho). The taxoids of general formula (I) in which Z represents a radical of general formula (II) manifest significant inhibitory activity with respect to abnormal cell proliferation, and possess therapeutic properties permitting the treatment of patients having pathological conditions associated with abnormal cell proliferation. The pathological conditions include the abnormal cell proliferation of malignant or non-malignant cells of various tissues and/or organs, comprising, without implied limitation, muscle, bone or connective tissue, the skin, brain, lungs, sex organs, the lymphatic or renal systems, mammary or blood cells, liver, the digestive system, pancreas and thyroid or adrenal glands. These pathological conditions can also include psoriasis, solid tumours, cancers of the ovary, breast, brain, prostate, colon, stomach, kidney or testicles, Kaposi's sarcoma, cholangiocarcinoma, choriocarcinoma, neuroblastoma, Wilms' tumour, Hodgkin's disease, melanoma, multiple myeloma, chronic lymphocytic leukaemia and acute or chronic granulocytic lymphoma. The taxoids according to the invention are especially useful for the treatment of cancer of the ovary. The taxoids according to the invention may be used to prevent or delay the appearance or reappearance of the pathological conditions, or to treat these pathological conditions. The taxoids according to the invention may be administered to a patient according to different dosage forms suited to the chosen administration route, which is preferably the parenteral route. Parenteral administration comprises intravenous, intraperitoneal, intramuscular or subcutaneous administration. Intraperitoneal or intravenous administration is more especially preferred. The present invention also comprises pharmaceutical compositions containing at least one taxoid of general formula (I), in a sufficient amount suitable for use in human or veterinary therapy. The compositions may be prepared according to the customary methods, using one or more pharmaceu|tically acceptable adjuvants, vehicles or excipients. Suitable vehicles include diluents, sterile aqueous media and various non-toxic solvents. Preferably,, the compositions take the form of aqueous solutions or suspensions, injectable solutions which can contain emulsifying agents, colourings, preservatives or stabilizers. However, the compositions may also be provided in the form of tablets, pills, powders or granules which can be administered via the oral route. The choice of adjuvants or excipients may be determined by the solubility and the chemical properties of the compound, the particular mode of administration and good pharmaceutical practice. For parenteral administration, sterile, aqueous or non-aqueous solutions or suspensions are used. For the preparation of non-aqueous solutions or suspensions, natural vegetable oils such as olive oil, sesame oil or liquid petroleum, or injectable organic esters such as ethyl oleate, may be used. The sterile aqueous solutions can consist of a solution of a pharmaceutieally acceptable salt dissolved in water. The aqueous solutions are suitable for intravenous administration provided the pH is appropriately adjusted and the solution is made isotonic, for example with a sufficient amount of sodium chloride or glucose. The sterilization may be carried out by heating or by any other means which does not adversely affect the composition. j It is clearly understood that all the compounds participating in the compositions according to the invention must be pure and non-toxic in the amounts used. The compositions can contain at least 0.01 % of therapeutically active compound. The amount of active principle in a composition is such that a suitable dosage can be prescribed. Preferably, the compositions are prepared in such a way that a single dose contains from 0.01 to 1000 mg approximately of active principle for parenteral administration. The therapeutic treatment may be performed concurrently with other therapeutic treatments including antineoplastic drugs, monoclonal antibodies, immunotherapy or radiotherapy or biological response modifiers. The response modifiers include, without implied limitation, lymphokines and cytokines such as interleukins, interferons (a, @ or S) and TNF. Other chemotherapeutic agents which are useful in the treatment of disorders due to abnormal cell proliferation include, without implied limitation, alkylating agents, for instance nitrogen mustards such as mechlorethamine, cyclophosphamide, melphalan and chlorambucil, alkyl sulphonates such as busulfan, nitrosoureas such as carmustine, lomustine, semustine and streptozocin, triazenes such as dacarbazine, antimetabolites such as folic acid analogues, for instance methotrexate, pyrimidine analogues such as fluorouracil and cytarabine, purine analogues such as mercaptopurine and thioguanine, natural products, for instance vinca alkaloids such as vinblastine, vincristine and vindesine, epipodophyllotoxins such as etoposide and teniposide, antibiotics such as dactinomycin, daunorubicin, doxorubicin, bleomycin, plicamycin and mitomycin, enzymes such as L-asparaginase, various agents such as coordination complexes of platinum, for instance cisplatin, substituted ureas such as hydroxyurea, methylhydrazine derivatives such as procarbazine, adrenocortical suppressants such as mitotane and aminoglutethimide, hormones and antagonists such as adrenocorticosteroids such, as prednisone, progestins such as hydroxyprogesterone caproate, methoxyprogesterone acetate and megestrol acetate, ©estrogens such as diethylstilboestrol and ethynyloestradiol, antioestrogens such as tamoxifen, and androgens such a: testosterone propionate and fluoxymesterone. The doses used for carrying out the methods according to the invention are those which permit a prophylactic treatment or a maximum therapeutic response. The doses vary according to the administration form, the particular product selected and features distinctive to the subject to be treated. In general, the doses are those which are therapeutically effective for the treatment of disorders due to abnormal cell proliferation. The taxoids according to the invention may be administered as often as necessary to obtain the desired therapeutic effect. Some patients may respond rapidly to relatively high or low doses, and then require low or zero maintenance doses. Generally, low doses will be used at the beginning of the treatment and, if necessary, increasingly stronger doses will be administered until an optimum effect is obtained. For other patients, it may be necessary to administer maintenance doses 1 to 8 times a day, and preferably 1 to 4 times, according to the physiological requirements of the patient in question. It"is also possible that some patients may require the use of only one to two daily administrations. In man, the doses are generally between 0.01 and 200 mg/kg. For intraperitoneal administration, the doses will generally be between 0.1 and 100 mg/kg, preferably between 0.5 and 50 mg/kg and still more specifically between 1 and 10 mg/kg. For intravenous administration, the doses are generally between 0.1 and 50 mg/kg, preferably between 0.1 and 5 mg/kg and still more specifically between 1 and 2 mg/kg. It is understood that, in order to choose the most suitable dosage, account should be taken of the administration route, the patient's weight, general state of health and age and all factors which may influence the efficacy of the treatment. The example which follows .illustrates a composition according to the invention. EXAMPLE 40 mg of the product obtained in Example 1 are dissolved in 1 cm3 of Emulphor EL 620 and l cm3 of ethanol, and the solution is then diluted by adding 18 cm3 of physiological saline. The composition is administered by perfusion over 1 hour by introduction in physiological solution. WE CLAIM 1. Process for the preparation of a taxoid of general formula (1) (Formula Removed) in which: Z rep-resents a hydrogen atom or a radical of general formuia: (Formula Removed) in which: R., represents a benzoyl radical optionally substituted by one or more identical or different atoms or radicals chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms, alkoxy radicals containing 1 to 4 carbon atoms or trifluoromethyl radicals, a thenoyl or furoyl radical or a radical R2-0-CO- in which R2 represents an alkyl radical containing 1 to 8 carbon atoms, an alkenyl radical containing 2 to 8 carbon atoms, an alkynyl radical containing 3 to 8 carbon atoms, a cycloalkyl radical containing 3 to 6 carbon atoms, a cycloalkenyl radical containing 4 to 6 carbon atoms or a bicycloalkyl radical containing 7 to 10 carbon atoms, these radicals being optionally substituted by one or more atoms or radicals chosen from halogen atoms and hydroxy1 radicals, alkoxy radicals containing 1 to 4 carbon atoms, dialkylamino radicals in which each alkyl portion contains 1 to 4 carbon atoms, piperidino or morphoiino radicals, 1-piparazinyl radicals (optionally substituted at the 4-position by an alkyl radical containing i to 4 carbon atoms or by a phenylalkyl radical in which the alkyl portion contains 1 tc 4 carbon atoms), cycloalkyl radicals containing 3 to 6 carbon atoms, cycloalkenyl radicals containing 4 to 6 carbon atoms, phenyl radicals (optionally substituted by one or more atoms or radicals chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms or alkoxy radicals containing 1 to 4 carbon atoms), cyano radicals, carboxyl radicals or alkoxycarbonyl radicals in which the alkyl portion contains 1 to 4 carbon atoms, a phenyl or α- or p-naphthyl radical optionally substituted by one or more atoms or radicals chosen from halogen atoms and alkyl radicals containing 1 to 4 carbon atoms or alkoxy radicals containing 1 to 4 carbon atoms, or a 5-membered aromatic heterocyclic radical, or a saturated heterocyclic radical containing 4 to 6 carbon atoms, optionally substituted by one or more alkyl radicals containing 1 to 4 carbon atoms, R3 represents an alkyl radical containing 1 to 8 carbon atoms, an alkenyl radical containing 2 to 8 carbon atoms, an alkynyl radical containing 2 to 8 carbon atoms, a cycloalkyl radical containing 3 to 6 carbon atoms, cycioalkenyl radicals containing 4 to 6 carbon atoms, a phenyl or a- or (ß-naphthyl radical optxonally substituted by one or more atoms or radicals chosen from halogen atoms and alkyl, alkenyl, alkynyl, aryl, aralkyl, alkoxy, alkylthio, aryloxy, arylthio, hydroxyl, hydroxyalkyl, mercapto , formyl., acyl, acylamino, aroylamino, alkoxycarbonylamino, amino, alkyiamino, dialkylamino, carboxyl, alkoxycarbonyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, cyano, nitro and trifluoromethyl radicals, or a 5-membered aromatic heterocycle containing one or more identical or different hetero atoms chosen from nitrogen, oxygen and sulphur atoms and optionally substituted by one or more identical or different atoms or radicals chosen from halogen atoms and alkyl, aryl, alkoxy, aryloxy, amino, alkyiamino, acylamino, dialkylamino, alkoxycarbonylamino, acyl, arylcarbonyl, cyano, carboxyl, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl and alkoxycarbonyl radicals, on the understanding that, in the substituents of the phenyl, a- or p-naphthyl and aromatic heterocyclic radicals, the alkyl radicals and the alkyl portions of the other radicals contain 1 to 4 carbon atoms, and that the alkenyl and alkynyl radicals contain 2 to 8 carbon atoms, and that the aryl radicals are phenyl or a- orß-naphthyl radicals. R4 represents an alkoxy radical containing 1 to 6 carbon atoms, an alkenyloxy radical containing 3 to 6 carbon atoms, an alkynyloxy radical containing 3 to 6 carbon atoms, a cycloalkyloxy radical containing 3 to 6 carbon atoms, a cycloalkenyloxy radical containing 3 to 6 carbon atoms, an alkanoyloxy radical in which the alkanoyl portion contains 1 to 6 carbon atoms, an aroyloxy radical in which the aryl portion contains 6 to 10 carbon atoms , an alkenoyloxy radical in which the alkenoyl portion contains 3 to 6 carbon atoms, an alkynoyloxy radical in which the alkynoyl portion contains 3 to 6 carbon atoms, a cycloalkanoyloxy radical containing 3 to 6 carbon atoms, an alkoxyacetyl radical in which the alkyl portion contains 1 to 6 carbon atoms, an alkylthioacetyl radical in which the alkyl portion contains 1 to 6 carbon atoms or an alkyloxycarbonyioxy radical in which the alkyl portion contains 1 to 6 carbon atoms, these radicals being optionally substituted by one or more halogen atoms or with an alkoxy radical containing 1 to 4 carbon atoms, an alkylthio radical containing 1 to 4 carbon atoms or a carboxyl radical, an alkyloxycarbonyl radical in which the alkyl portion contains 1 to 4 carbon atoms, a cyano or carbamoyl radical or an N-alkylcarbamoyl or N,N-dialkylcarbamoyl radical in which each alkyl portion contains 1 to 4 carbon atoms or, with the nitrogen atom to which it is linked, forms a saturated 5- or 6-membered heterocyclic radical optionally containing a second hetero atom chosen from oxygen, sulphur and nitrogen atoms, optionally substituted by an alkyl radical containing 1 to 4 carbon atoms or a phenyl radical or a phenylalkyl radical in which the alkyl portion contains 1 to 4 carbon atoms, or alternatively R.4 represents a carbamoyloxy or alkylcarbamoloxy radical in which the alkyl portion contains 1 to 4 carbon atoms, a dialkylcarbamoyloxy radical in which each alkyl portion contains 1 to 4 carbon atoms or a benzoyloxy radical or a heterocyclylcarbonyloxy radical in which radical the heterocyclic portion represents a 5- or 6- membered aromatic heterocycle containing one or more hetero atoms chosen from oxygen, sulphur and nitrogen atoms, R5 represents a hydrogen atom, Re represents a hydrogen atom, and R and R7 together form a bond, which process comprises: (a) reacting by known methods a compound of general formula: (Formula Removed) In which Y represents a leaving group and R4 as defined above with the 10-hydroxy group of a compound of general formula: (Formula Removed) or a corresponding compound in which the hydroxyl function at the 10-position is metalated by means of an alkali metal hydride, amide or alkylide, in which the compound of general formula (V), Z1 represents a hydrogen atom or a group protecting the hydroxyl function or a radical of general formula (IV) (Formula Removed) in which Ri and R3 are as defined above and Rs represents a group protecting the hydroxyl function, R5 and Re represent hydrogen atoms and R and R7 together form a bond to obtain a corresponding compound in which the 10-hydroxy group in the compound of general formula (V) is replaced by a group R4; and (b) when the corresponding compound obtained in (a) contains a protecting group represented by Z1 or Rs by a hydrogen atom by means of an inorganic acid in an aliphatic alcohol containing 1 to 4 carbon atoms at a temperature of between -10 and 20° C or by means of the hydrofluoric acid/ triethylamine complex, working in an inert oganic solvent at a temperature of between 0 and 50° C to obtain a compound of formula ;(I) in which Z represents a hydrogen atom or a radical of general formula (II). 2. A process for the preparation of a taxoid as claimed in claim 1 substantially as hereinbefore described. |
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421-del-2000-complete specification (granted).pdf
421-del-2000-correspondence-others.pdf
421-del-2000-correspondence-po.pdf
421-DEL-2000-Description (Complete).pdf
| Patent Number | 188470 | |||||||||
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| Indian Patent Application Number | 421/DEL/2000 | |||||||||
| PG Journal Number | 39/2002 | |||||||||
| Publication Date | 28-Sep-2002 | |||||||||
| Grant Date | 04-Jul-2003 | |||||||||
| Date of Filing | 10-Apr-2000 | |||||||||
| Name of Patentee | RHONE-POULENC RORER S.A. | |||||||||
| Applicant Address | 20, AVENUE RAYMOND ARON, 92160 ANTONY, FRANCE | |||||||||
Inventors:
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| PCT International Classification Number | A61K 31/00 | |||||||||
| PCT International Application Number | N/A | |||||||||
| PCT International Filing date | ||||||||||
PCT Conventions:
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