Title of Invention

"A METHOD FOR SYNTHESIS OF DENDRIMER POLYMERIC RESINS FOR SOLID PHASE ORGANIC SYNTHESIS"

Abstract This invention relates to a method for the synthesis of dendrimer polymeric resins for solid phase organic synthesis comprising suspension polymerization of the monomer, styrene and divinylbenzene crosslinker and crosslinker as herein described to form a polymer; preparing the Schiff base using a triamino moiety and a phenyl aldehyde; subjecting the said Schiff base to react with the polymer to obtain Schiff base attached polymer backbone, with two reactive dendritic sites S1 and S2; subjecting the said Schiff base attached polymer with two dendritic sites S1 and S2, wherein the number of dendritic sites can be increased by repeating steps (ii) & (iii) & addition of Schiff base moiety to the CPT terminals followed by attachment of PEG units, to the step of chloromethylation to obtain chloromethylated phenyl terminals [CPT1 & CPT2]; attaching PEG to the dentritic site via Na derivative of PEG (partially converted Na and OH terminal PEG) or amino attached PEG chains.
Full Text FIELD OF INVENTION
This invention relates to a method for the synthesis of dendrimer polymeric resins for solid phase organic synthesis
BACKGROUND OF INVENTION
In 1963 Merrifield first described in the literature his method of 'solid phase' peptide synthesis. In this method the first amino acid residue of the peptide to be synthesized is bound to polystyrene beads through an ester linkage formed using carboxyl group of the amino acid. As a consequence the peptide subsequently synthesized is attached to the beads via the carboxyl terminus. The polystyrene beads are cross linked and are therefore, totally insoluble in organic solvents. Thus, at each stage in the synthesis the supported peptide can be separated cleanly and easily from the other species present. At the end of the synthesis the peptide produced is detached from the polymer support by cleaving the ester linkage. Merrifield first synthesized a tetrapeptide using this approach, but he had soon developed a machine for automated peptide synthesis, and synthesized ribonuclease A and enzyme with 124 amino acid residues. This novel approach so revolutionalised peptide synthesis that Merrifield was awarded the 1984 Nobel Prize for chemistry.
Both solid phase and solution phase synthetic methods are used for combinatorial chemistry. To date the majority of small molecule combinatorial libraries have been assembled by solid phase organic synthesis [SPOS]. One advantage of SPOS is the complete removal of purification procedure, therefore making it particularly useful for multiple-automated synthesis, and the completion in each step of the reaction is with high rate. In SPOS, molecules are built up of the end of the spacer group, which serves to
functional loading and biocompatibility compared with known, national and international PEG-based resins. The present work introducing one class of polymer gel resins, especially for Solid Phase Organic Synthesis (SPOS) with high yield and purity. This gel type resin is a family of PEG-PS, obtained by modification of styrene backbone, by attaching the dendrimer Schiff base moiety for multiple PEG loading chains to styrene, in DVB crosslinked polystyrene system. The present class of resins completely changed the hydrophobicity of styrene and converted to solvent-like and obtained in bead form is very useful to solid phase organic synthesis and giving highly yield and purity to peptide.
OBJECTS OF THE INVENTION
An object of the invention is to propose a novel class of gel-like dendrimer polymeric resins for Solid Phase Organic Synthesis.
Another object of the invention is the synthesis of highly swollen, solvent-like polymer with high chemical and mechanical stability and high flexibility and biocompatibility for Solid Phase Organic Synthesis.
Further object of the invention is the synthesis of the resin of uniform hydrophilic/hydrophobic balances to obtain the products with high yield and purity in SPOS.
Still further object of the invention is the synthesis of dendritic polymer resin of high functional loading.
SUMMERY OF THE INVENTION
According to this invention there is provided a method for the synthesis of dendrimer polymeric resins for solid phase organic synthesis comprising:-
i) suspension polymerization of the monomer, styrene and
divinylbenzene crosslinker and crosslinker as herein described to form a polymer;
ii) preparing the Schiff base using a triamino moiety and a phenyl aldehyde;
iii) subjecting the said Schiff base to react with the polymer to obtain Schiff base attached polymer backbone, with two reactive dendritic sites S1 and S2;
iv) subjecting the said Schiff base attached polymer with two dendritic sites S1 and S2, wherein the number of dendritic sites can be increased by repeating steps (ii) & (iii) & addition of Schiff base moiety to the CPT terminals followed by attachment of PEG units,
to the step of chloromethylation to obtain chloromethylated phenyl terminals [CPT1 & CPT2];
v) attaching PEG to the dentritic site via Na derivative of PEG
(partially converted Na and OH terminal PEG) or amino attached PEG chains.
PaTTAILICP PBiSKTRfPTIQW OF INYKNTIO1H
VIN-GEL resins are new polymeric fuppctts for SPOSvvith new strategy.
Styrene-DVB crossmiked polymer was prepared by suspension polymerization with
various crosslink densities.
After preparation, of the polymer, the dendritic functional sites were incorporated after
ohkxometbylation ofstyrene units.
The dendritic sites ware prepared by me addition of triamine and phony! aldehyde to fbnn
schiff base.
The schiff base dendritasto were ttra^
More dendritic sites ware prepared by this method and the Naptenninatod (partial
hydroxy), or ammo terminatod PEG was incorporated to cUoromothylated terminals,
getting high functional loading flexible reams.
The polymer resins were characterize
Scanning etoobon nuarograph explains the moiphology of me entire system.
The oapaouy of functional site m each, step is same mriinatmg the oompkte oonvcrsiott of
functional site of newly developed porymerio system.
IR explains the stability of the ream and ft mdmua^ mst me newly develo])ed gel type
system is nwchnucmlr/ stable and suit for SPOS.
HMPP •m4 IfMP A KfflHr WM*>
The high swelhqg cosracteristico, atabiUty aiid wh«nt-hl» nature m various reagents and
solvents make the new ream, one of me best substitelesm solid phase oigamsynmesis.
The high swelling dsgackrisUtts of flu* resin in water make it one of the best supports
^fc_ _ ^^. * * —• • _*a_ * According to this invention, them is provided a novel olaas of dendrtic polymer gel resins
for coinbmab^soU phase orgsnksynQM
The hydraphobiBity of the present PS-DVB mm v fofly changed by mteodwing highly
fkndbto PEO-«riL AM to ooimn»c^
sm modified by introducmg PBO units, by modifying the DVB aoailiaki or styrene
But hoe is isftodwJBg • now type of mfh fbDatkn kNMiing 'sotvcnt-liko'
reams by grafting more men one PEG-onit to styrane backbone through ohloromethyl
group.
[A]
The PS-OVB (1-2 H) raains were prepared by known siispomitn potymerizslioa and it is
clik)ioaiB%latad fay nimg ch^^
IBJ
Hie
(CJ
After preparing fhe sohnTbaae, it allows to react wiu cUoioniefhyl gtc«i^ of poiystyrane-
DVB. Then Schiff base attached polystyrene backbone, wo are getting two reactive
dandrtio sites S] and sj.
Fourth step
Diflbnnt types of PBO with diflbnot moteculsr vmght (100-1500) woe used. The
sodium derivative of PEG woe prepared by NaH in THF at 45^C (getting partially
converted sodium derivative), and Oikro PEG wore praparad by traating PEG with
-7-
SOCla at 100 °C. The ammo FEO was also pnpamd by testing me chkxo PEO wim
potassium phthahmide at DMF at HXPc fo&mri by treating wto hydwmo hydmte in
presence of ethanol.
Fifth step
After the mini step |C), two deadrbo sales s( awl *a an mam followed by
, gettmg two chkxomethlated phenyl termmab [CPTi ft CPT2].
After attaching me two [CPTi A J, again following the aaoond and mmi atop [B] A (C]
and addition of mis schiff base moiety to me two [CPT]. we are gettmg four CPT
terminals [CPTS ft CPT4]
The same protoools were followed for bjgntr dendnmer units.
Method 1. Oeocrttion 1.
: of PEO to two fCPTi ft CPTal YIN-GEL'
After attachment of CPTiACPT;
-QH terminal PEO) or ammo attached PEG chaiw(10()-l 500) (idw fourth rtop.D)wc»re
treated wim CPTi ft CPT2, we am getting me free -OH or ammo termmal PEG unite.
From the lime -OH or amsao terminal PEO, we can attach spacosh1»HMPA and HMPB
etc... and can used for Solid Phase Organic Synthesis.
Method 2. Generation 2.
ICPT, T.T. A T^l V1N-GELB
After attaohmant of CPT,,T2,T3 ftCPT^ the Na derivative of PEO (partially oonv«
Na and-OH terminal PEG) or ammo attaclied PEG chaim(wfe fourth step, D) were
-8-
treatedwimCPTi,T9,T3 & CPT*. we are getting me free -OH or amino tennmal PEG
units. Pram die five -Off or amino tanmnal PEG, we oan attaoh spacers tike HMPA and
HMPB etc...and oan used for Solid Phase Organic SyisJmis. For high degree ftnoUoiwl
loading the PEG attachment generations are repeated.
The invention win be explained in greater details wim the help of the examples.
EXAMPLE 1:
Linker attached PS-DVB, Tent* Gel, Jand* Jel, PEGA, reams, used for the synthesis of
die well known C-tanninel region of AGP fragment (65-74), **~*fX6*A many of me
sequence dependant pgnbhms which may be enoountered during me course of solidphase
peptide synthesis. Many problems mat have led to poor synthetic results could be
traced back to the internal development of secondary structure, which competes
specifically with the desired amide* bond Jbnnaoon. Segments mat promote inter chain
aggregation result in dramatic reduction in amino group accessibility. The combinatorial
library assays were followed in the proposed VIM-GEL resins and compared with
attached PS-DVB, Tenta Gel, Anda Jet resins. In all PS-DVB ge» iwins the swelling and
functional loading of the YIN-GEL resins is found to be fow to fro timci greater than
known commercially available reams, m the synthesis of the difficult AGP sequence
in such as way mat the quantity of gtycme in a respective leactioa vessel was the same.
This was to make sure that the reaction oondhions were uniibra\ wbm the acyurtkn was
carried out with respective amino acid and coupling raageiR*. AD coupling leaotkra were
canied out using 4eq. excess of respective amino acid. HOBT. HBTU and DIEA. The
total amount of these reagents required to incorporate an ammo acid into these resins
were weighed, dnsotved in DMF and then distributed equally to each synthesizer. This
further ensured identical coupling conditions. After synthesis, N-terminal Fmoc
protection was removed from the corresponding resins under the same cleavage
conditions. The ACP fragment obtained was characterized by HPLC and MALDf-TOF
MS. In the YIN-GEL resins the yield obtained is above 90% compared with other Tenta
Gel and Janda Jel under the same synthetic conditionB.
A now clams of 'solvent-ilk*' dondrlmor rosins, VIN-O1L for
Solid Pttaso Organic Synthosl*
FIELD OF INVENTION
This invention relates to a novel class of gel-like dendrimer polymeric resins for solid
phase organic synthesis
BACKGROUND OV INVENTION:
In 1963 Merrifield first described in the literature his method of 'solid phase* peptide
synthesis, hi this method (he first ammo acid residue of the peptide to be synthesized is
bound to polystyrene beads through an ester linkage formed using carboxyl group of the
amino acid. As a consequence the peptide subsequently synthesized is attached to the
beads via the carboxyl terminus. The polystyrene beads arc crosslinkcd and arc therefore.
totally insoluble in organic solvents Thus, at each stage in die synthesis the supported
peptide can be separated cleanly and easily from the other species present. At the end of
the synthesis the peptide produced is detached from the polymer support by cleaving the
ester linkage Memiiekl first synthesized a tetrapeptide using this approach, but he had
soon developed a machine for automated peptide synthesis, and synthesized ribonucleasc
A and enzyme with 124 amino acid residues. This novel approach so revolutjonalised
peptide synthesis that Merrifield was awarded the 1984 Nobel Prize for chemistry.
Both solid phase and solution phase synthetic methods are used for combinatorial
chemistry. To date the majority of small molecule combinatorial libraries have been
assembled by solid phase organic synthesis [SPOS]. One advantage of SPOS is the
complete removal of purification procedure, therefore making it particularly useful for
multiple-automated synthesis, and the completion in each step of the reaction is with high
rate. In SPOS, molecules are built up of the end of the spacer group, which serves to

attach the reaotant molecule to the resin bead The resin is uniformly funotionalised, the
amount of reactive group on the bead surface and in the bead interior can be easily
estimated by volumetric calculations. Most of the reaction sites (99 %) are buried interior
portion of the polymer matrix,
Merrifield first introduced the concept of SPOS by utilizing a chloromethyistyreno solid
support for pcptide synthesis, ftwkniiinanlh/, SPOS has fevored the use of styrcnc-bascd
resins because of their thermal, chemical, and mechanical stability. Despite their
widespread use, 3iynme-divinylhen/«ne polymer supports PS-DVB [Merrifield rosin]
exhibit limited swelling in highly polar solvents such as water. Reduced accessibility of
polar reagents into the polymer matrix often gives low-yielding on-boad reactions and, in
addition severely restricts the usage of this polymer support in aqueous bioassays. In
attempts to circumvent these limitations, a variety of linkers have been attached to PSDVB
support to optimize theit properties for specific applications. While linkers modify
the local chemical environment around the reactive sites of these resins, they do not have
a significant effect upon the intrinsic hydrophobicily of polystyrene-based resins.
The current surge in parallel array synthesis far the production of small molecule libraries
has generated keen interest in the application of .solid-supported reagents and catalysts in
solid phase chemistry. Polyethylene glycol grafted polystyrene (PS-g-PEG) resins have
drawn much attention in many research areas such as pharmaceutical chemistry, organic
chemistry, biochemistry, and biochemical engineering. One of the most interesting
applications of PS-g-PKG resin can be found in the building of combinatorial libraries of
pepudes, nucleotides and small organic molecules, which have become a very powerful
tool for the development of therapeutic agents.
PS-g-PEG resins show good swelling properties in various kinds of solvent, such as
alcohols, diehloromethane, DMF, THF, acetonitrile and water. These properties are due
to the amphiphiUc character of the resins. The polystyrene backbone of the PS-g-PEG
resins is hydrophobic and exerts strong mechanical and chemical stability. The grafted

PFXJ moieties show good compatibility with biological systems are hydrophilic in nature
and swell well in hydrophilic solvent such as alcohols and water. Therefore the amount of
PEG grafted to polystyrene backbone in PS-g-PEG resin is important factor affecting
many physical properties as well as chemical properties. As a polymer support, the
swelling properly is very important when used in organic synthesis. The reactions are
heterogeneous in nature, which means that if a reagent should read with any active site at
the interior of the polymer matrix, it has to diffuse from the bulk phase to the resin
matrix. The high swelling property of the polymer chain induces the reagent to diffuse
quickly inside the rmin and the reaction proceeds smoothly in a more homogeneous
phase. Since the inception of the solid phase method for the preparation of peptides and
proteins, enormous work has focused on addressing the impediments to high yield, highpurity
synthesis. Many coupUng/deprotection problems are known to be sequence, not
amino acid dependent These difficult sequences are generally attributed to the formation
of fi-sheet structure by the resin bound pcptide. An alternative route to increasing the
yield of stepwisc assembly focused on improving the polarity of the original PS-DVB
resin to afford greater accessibility of the growing peptide chains to acylation and
deprotection. Resins with more polar backbone structures, most notably potyacrylamide,
polyethylene glycol (PHG)-poly8ryrene graft, and PEG-crosslinked acrlylate/aciylamide
resins, polyoxyethylene and polyoxypropylene resins- POEPS & POEPOP, Janda Jel are
found varying degree of reaction rate in peptide synthesis.
Comparing all of the available PEG-bascd polymer support, the modification of the
standard unique PS-DVB Merrifield resin is obtained by introducing PEG units in styrene
backbone moiety and DVB crosslinker. hi these criteria Tenta Gel and Janda Jel is
commercially important The introduction of PEG units permits easy sorvation in polarnonpolar
solvents. By changing the styrene backbone to amide leads to affect the
mechanical stability So to rectifying all the existing defects and drawbacks in PS-DVB
resin, introducing flexible PEG chains as dendrimer sites through schiff base linkage. The
attachment of multiple dendritic PEG units makes the PS-DVB system completely
solvent like gel. The main advantage of the proposed gel resins is doe to its high

functional loading and biocompatibility compared with known, national and international
PEG-based resins. The present work introducing one class of polymer gel resins,
especially for Solid Phase Organic Synthesis [SPOSj with high yield and purity. This gel
type resin is a family of PEO-PS, obtained by modification of styrcnc backbone, by
attaching the dendnmer *cmff base moiety for multiple PEG loading chains to stymie, in
DVB crosslinked polystyrene system. The present class of resins completely changed the
hydrophobicity of styrene and converted to solvent-like and obtained in bead form is very
useful to solid phase organic synthesis and giving high yield and purity to peptide.
OBJECT OF THE INVENTION
An object of the invention is to propose a novel class of gel-like dendrimer polymeric
resins for Solid Phase Organic Synthesis.
Another object of the invention is the synthesis of highly swollen, solvent-like polymer
with high chemical and mechanical stability and high flexibility and biocompatibility for
Solid Phase Organic Synthesis
Further, object of the invention is the synthesis of the train of uniform hydrophilic
/hydrophobic balances to obtain the products with high yield and purity in SPOS.
Still further object of the invention is the synthesis of dcndrtic polymer resin of high
functional loading.
SUMMARY OF THE INVENTION
to titttt invunfton a tiovw! dare of gol-liko dendnmer polymeric rosins for solid
phase organic synthesis and a method for the synthesis of dendnmer polymeric resins
comprising:
(i) polymerizing the monomer and crosslinker to form a polymer,
(u) preparing the schiff base using a triamino moiety and a phenyl aldehyde;
(iii) subjecting the said schiff base to react with the polymer to obtain schiff
base attached polymer backbone, with two reactive dendritic sites si and
s2;
(iv) subjecting the said schiff base attached polymer with two dendritic sites si
and 2, to the step of ehloramethylation to obtain chloromethylated phony 1
terminals JCPT1 & CPT2J
(V) attaching PEG to the dendritic site via Na derivative of PEG (partially
converted Na and-OH terminal PEG) or amino attached PEG chains.
DETAILED DESCRIPTION OF INVENTION
VIN-GEL resins are new polymeric supports for SPOS with new strategy.
Styrene-DVB crosshnked polymer was prepared by suspension polymerization with
various crosslink densities.
After preparation of the polymer, the dendritic functional sites were incorporated after
chloromethylation of styrene units.
The dendritic sites were prepared by the addition of triamine and phenyl aldehyde to form
schiff base.
The schiff base dendritic sites were incorporated to chloromethylated polystyrene
More dendritic sites wore prepared by this method and the Na-terminated (partial
hydroxy), or amino terminated PEG was incorporated to chloromethylated terminals,
getting high functional loading flexible resins.
The polymer resins were characterized using IR, C NMR and SEM technique.
Scanning electron micrograph explains the morphology of the entire system.
The capacity of functional site tn each step is same indicating the complete conversion of
functional site of newly developed polymeric system.
1R explains the stability of the resin and it indicating that the newly developed gel type
system is mechanically stable and suit for SPOS.
HMPB and HMPA linker were used as linker for the present investigations.
The high swelling characteristics, stability and solvent-like nature in various reagents and
solvents make the new resin, one of the best substitutes in solid phase organic synthesis.
The high swelling characteristics of this resin in water make it one of the best supports
for studying the immobilized enzyme kinetics
VIN-GEL resins for combinatorial Solid Phmre Organic Smthe»i»
According to this invention, there is provided a novel class of dendrtic polymer gel resins
for combinatorial solid phase organic synthesis based on polystyrene.
The hydrophobicity of the present PS-DVB resin is fairy changed by introducing highly
flexible PEQ-unit. AH the commercially available PS-DVB graft PEG resins, the resins
are modified by introducing PEG units, by modifying the DVB crosslinks or atyrene
backbone. But here is introducing a new type of high function loading 'solvent-like*
resins by grafting more than one PHO-unit to styrene backbone through chloromethyl
group.
FirM itep [A]
The PS-DVB (1-2 %» resins wore prepared by known suspension polymerization and it is
chlonnnethylated by using chlonnnethy Imeihyldner with Lewis acid catalyst at 50 °C
Second step (B]
The sehiff base is prepared by using a triamino moiety and a phenyl aldehyde.
Third step |C]
After preparing the schirT base, it allows to react with chloromethyl group of polystyrene-
DVB. Then SchirT base attached polystyrene backbone, we are getting two reactive
dendrtic sites s, and so
Fourth step [D]
Different types of PEG with different molecular weight (100-1500) were used. The
sodium derivative of PKG wen? prepared by NaH in THF at 45°C (getting partially
converted sodium derivative), and Chloro PEG were prepared by treating PEG with
SOC12 at 100 °C. The amino PEG was also prepared by treating the chloro PEG with
potassium phthalimuie at DMF at 100°C followed by treating with hydrazine hydrate in
presence of ethanol
Fifth step
After the third step |C], two dendttic sites ^ and 93 «» then followed by
chlorooiathytation, getting two chloromethlaied phenyl terminals [CPTj & CPT2J.
Slirh step
After attaching the two (CFf, & 2J, again following the second and third step [B] & [C]
and addition of this sehiff base moiety to the two [CPT]. we are getting four CPT
terminals |CPr3& CP14)
The same protocols were followed for higher dendrimer units.
Different generation of VIN-OEL resins by PEG- attachment
Method 1. Generation 1
Attachment of PEG to two [CPF, & CPT21 VIN-GE1,A
After attachment of CPT, & CPT2, the Na derivative of PEG (partially converted Na and
OH terminal PEG) or amino attached PEG chains (100-1500) (refer fourth step. D) were
treated with CPTj & CPT?, we are getting the free -OH or amino terminal PEG units.
From the tree OH or amino terminal PEG, we can attach spacers like HMPA and HMPB
etc... and can used for Solid Phase Organic Synthesis.
Method 2, Generation 2
Attachment of PEG to four ICPT, £ £ & JJ.VIN-GEL B After attachment of OPT, 12 IS & CPT4, the Na derivative of PEG (partially converted
Na and -OH terminal PEG) or amino attached PEG chains (refer fourth step, D) were

treated with CFrt, Ta. T, & CFT*. we are getting the free OH or amino terminal PEG
units. From the Iree OH or ammo terminal PEG, we can attach spacers like HMPA and
HMPB etc...and can used for Solid Phase Organic Synthesis. For high degree functional
loading the PEG attachment generations are repeated.
The invention will be explained in greater details with the help of the examples.
EXAMPLE 1:
Linker attached PS-DVB, Tenta Gel, Janda Jei, PEGA, resins, used for the synthesis of
the well known C-termmal region of ACP fragment (65-74), exemplified many of the
sequence dependant problems which may be encountered during the course of solidphase
peptide synthesis Many problems that have led to poor synthetic results could be
traced back to the internal development of secondary structure, which competes
specifically with the desired amide bond formation. Segments thai promote inter chain
aggregation result in dramatic reduction in amino group accessibility. The combinatorial
library assays were followed in the proposed VIN-GKL resins and compared with
attached PS-DVB, I eni« Gel, Janda Jel resins. In all PS-DVB gel resins the swelling and
functional loading of the VIM-GEL resins is found to be four to five times greater than
known commercially available resins, hi the synthesis of the difficult ACP sequence
synthesis, the above-mentioned n&inx were studied. The respective rosins were weighted
in such as way that the quantity of glycine in a respective reaction vessel was the same.
This was to make sure that the reaction conditions were uniform when the acylation was
carried out with respective amino acid and coupling reagents. All coupling reactions were
carried out using 4eq, excess of respective amino acid, HOBT, HBTTJ and DIEA. The
total amount of these reagents required to incorporate an amino acid into these resins
were weighed, dissolved in DMF and then distributed equally to each synthesizer. This
further ensured identical coupling conditions. Alter synthesis, N-terminal Fmoc
protection was removed from the corresponding resins under the same cleavage
conditions. The ACP fragment obtained was characterized by HPLC and MALDI-TOF
MS hi the VIN-GEL resins the yield obtained is above 90% compared with other Tenta
(iel and Janda Jel under the same synthetic conditions.
-9-
EX AMPLE 2:
efficiency of linker attached VIN-OEL resins were studied by synthesizing the
Endothelin Fl\ and KTB receptor antagonists BQ-123 and big endothelin fragment
having cyclic peptide bond. The peptidc were also synthesized in commercially available
PS-DVB PEG-gnA Ten** Gel, J«nd« Jet The peptidc obtained in this newly developed
solvent-like VIN-GEL is pure with high yield. The respective resins with same degree of
C-iermirmi amino aekl substitution were used for the study. In a typical coupling reaction
total amino acid and coupling reagents required for both resins were weighed together,
dissolved in DtViF and then distributed equally to both resins The coupling time gives
was 40 min. Only a single coupling reaction was performed to incorporate a single amino
acid. After synthesis, the peptide was cleaved from the support in 4h by adding TFA
scavenger mixture, '(lie crude peptide obtained from the two resins was analyzed by
HPLC. The peptide synthesized on VIN-OEL resin gave only one major peak compared
with other rcsms, suggesting that the coupling and deprotection steps were driven to
completion,






WE CLAIM:
1. A method for the synthesis of dendrimer polymeric resins for solid phase organic synthesis comprising: -
i) suspension polymerization of the monomer, styrene and divinylbenzene crosslinker and crosslinker as herein described to form a polymer;
ii) preparing the Schiff base using a triamino moiety and a phenyl aldehyde;
iii) subjecting the said Schiff base to react with the polymer to obtain Schiff base attached polymer backbone, with two reactive dendritic sites S1 and S2;
iv) subjecting the said Schiff base attached polymer with two dendritic sites S1 and S2, wherein the number of dendritic sites can be increased by repeating steps (ii) & (iii) & addition of Schiff base moiety to the CPT terminals followed by attachment of PEG units,
to the step of chloromethylation to obtain chloromethylated phenyl terminals [CPT1 & CPT2];
v) attaching PEG to the dentritic site via Na derivative of PEG (partially converted Na and OH terminal PEG) or amino attached PEG chains.
2. A novel class of gel-like dendrimer polymeric resins as claimed in claim 1, wherein the dendrimer polymeric resins is for solid phase organic synthesis.
3. The novel class of polymeric resins as claimed in claim 2, wherein said resin used for solid phase organic synthesis comprises of polystyrene backbone having multiple dendritic PEG units.
4. The novel class of polymeric resins as claimed in claim 2, wherein the high coupling rate of system as herein described uses full expansion of reaction medium which gives high biocompatibility.



Documents:

3343-del-2005-Abstract (10-06-2011).pdf

3343-DEL-2005-Abstract-(09-06-2011).pdf

3343-DEL-2005-Abstract-(17-06-2011).pdf

3343-DEL-2005-Abstract-(25-11-2008).pdf

3343-del-2005-abstract.pdf

3343-del-2005-Amended Pages of specification (10-06-2011).pdf

3343-del-2005-Claims (10-06-2011).pdf

3343-DEL-2005-Claims-(09-06-2011).pdf

3343-DEL-2005-Claims-(17-06-2011).pdf

3343-DEL-2005-Claims-(25-11-2008).pdf

3343-del-2005-claims.pdf

3343-DEL-2005-Correspondence Others-(09-06-2011).pdf

3343-DEL-2005-Correspondence Others-(17-06-2011).pdf

3343-del-2005-Correspondence-others (10-06-2011).pdf

3343-DEL-2005-Correspondence-Others-(13-01-2009).pdf

3343-DEL-2005-Correspondence-Others-(25-11-2008).pdf

3343-del-2005-correspondence-others.pdf

3343-del-2005-Description (Complete)-(17-06-2011).pdf

3343-DEL-2005-Description (Complete)-(25-11-2008).pdf

3343-del-2005-description(complete).pdf

3343-del-2005-form-1 (10-06-2011).pdf

3343-DEL-2005-Form-1-(13-01-2009).pdf

3343-DEL-2005-Form-1-(25-11-2008).pdf

3343-del-2005-form-1.pdf

3343-del-2005-form-18.pdf

3343-del-2005-Form-2 (10-06-2011).pdf

3343-DEL-2005-Form-2-(09-06-2011).pdf

3343-DEL-2005-Form-2-(17-06-2011).pdf

3343-DEL-2005-Form-2-(25-11-2008).pdf

3343-del-2005-form-2.pdf

3343-del-2005-form-3.pdf

3343-del-2005-form-9.pdf

3343-DEL-2005-GPA-(13-01-2009).pdf


Patent Number 248244
Indian Patent Application Number 3343/DEL/2005
PG Journal Number 26/2011
Publication Date 01-Jul-2011
Grant Date 29-Jun-2011
Date of Filing 12-Dec-2005
Name of Patentee DEPARTMENT OF BIOTECHNOLOGY
Applicant Address BLOCK-2,7TH FLOOR, CGO COMPLEX, LODHI ROAD, NEW DELHI-110003
Inventors:
# Inventor's Name Inventor's Address
1 G.S. VINOD KUMAR RAJAIV GANDHI CENTRE FOR BIOTECHNOLOGY, POOJAPPURA, THIRUVANTHA PURAM-695014
PCT International Classification Number C07C 213/00
PCT International Application Number N/A
PCT International Filing date
PCT Conventions:
# PCT Application Number Date of Convention Priority Country
1 NA