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