Polyethylene glycol , solid-phase synthesis

The same approach was readily adaptable to solid-phase synthesis. A small library of unnatural derivatives of 140 was prepared with variation of the configuration and nature of R1 and R4 and with substitution on the benzene ring <2000JC0186>. Three natural alkaloids, Verrucine A, B, and Anacine, were synthesized by a similar pathway and the pyrazino[2,l- ]quinazoline as opposed to the benzodiazepine structure of Anacine was proved <2001JNP1497>. Fiscalin B and other derivatives were prepared by solid-phase synthesis using polyethylene glycol (PEG) resin <2002USP6376667>. 

Poly(ethylene glycol) supported liquid-phase syntheses by both the reaction of (polyethylene glycol (PEG))-supported imines with nitrile oxides, generated in situ from aldoximes, (300) and 1,3-dipolar cycloadditions of nitrile oxide, generated in situ on soluble polymers with a variety of imines (301, 302) have been described. The solid-phase synthesis of 1,2,4-oxadiazolines via cycloaddition of nitrile oxide generated in situ on solid support with imines has also been elaborated (303). These syntheses of 1,2,4-oxadiazolines provide a library of 1,2,4-oxadiazolines in good yields and purity. 

S Kates, NA Sole, M Beyermann, G Barany, F Albericio. Optimized preparation of deca(L-alanyl)-L-valinamide by 9-fluorenylmethoxyloxycarbonyl (Fmoc) solid-phase synthesis on polyethylene glycol-polystyrene (PEG-PS) graft supports, with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) deprotection. Pept Res 9, 106, 1996. 

Scheme 7 (a) Synthesis of [3-lactam bound to a soluble/insoluble polyethylene glycol mono-methylether polymeric mallix. (b) Stereoselective and solid phase synthesis of [3-lactam... 

Bradley described the first solid-phase synthesis of PAMAM dendrimers in 1997 [220]. To this end, phthaloyl-protected norspermidine was coupled to aminomethyl functionalised polystyrene-polyethylene-glycol resin ((PS-PEG)-NH2) through an acid-labile linker (see Fig. 23). PAMAM dendrons were assembled by treating deprotected scaffold-bound resin 24 first with an excess of methyl acrylate... 

Meldal M. PEGA a flow stable polyethylene glycol dimethyl acrylamide copolymer for solid phase synthesis. Tetrahedron Lett. 1992 33 3077-3080. 

Dipolar cycloaddition of polyethylene glycol-supported azide with various dipolarophiles followed by acidic cleavage afforded 4- and 5-substituted-1,2,3-triazoles 05T4983>. Trimethylsilyl-directed 1,3-dipolar cycloaddition reactions in the solid-phase synthesis of 1,2,3-triazoles have been developed <05OL1469>. 

Barany, G., Alberido, F., Kates, S.A. and Kempe, M. (1997) Polyethylene glycol)-Containing Supports for Solid-Phase Synthesis of Peptides and Combinatorial Organic Libraries. In ACS Symposium Series 680. Polyethylene glycol) Chemistry and Biological Applications (eds J.M. Harris and S. Zalipsky), American Chemical Sodety, Washington, DC, pp. 239-64. 

An alternative method to overcome the limitations of solid phase synthesis is the use of isolation tags. For example, long polyethylene glycol (PEG) chains are... 

Liquid-phase peptide synthesis resembles the solid-phase method (see Chapter 2) in that the synthesis takes place on a polymer backbone (i.e., polyethylene glycol). However, the polymer is soluble in the solvent system used, so that a homogenous reaction results. This methodology has found far less use than the analogous solid-phase synthesis. 

A number of other chemical modifications of polymers have been performed under phase transfer conditions Including the cleavage of peptides from a solid support in a Merrlfield solid phase synthesis (Ref. 65), and the hydrolysis of methyl methacrylate in the presence of catalysts such as polyethylene glycol or 18-crown-6 (Ref. 66). Hradil and Svec (Ref. 67) have very recently completed a study of the reaction of hydrolyzed copoly(glycldyl methacrylate ethylene dimethacrylate) with propane sultone in the presence of tetrabutyl ammonium hydroxide. While the reaction gave only 25% yield in the absence of catalyst, a drastic improvement to 68% conversion was observed when a phase transfer catalyst was added. 

Initial solid phase synthesis25 was carried out on Merrifield s resin (1 % crosslinked chloromethylated styrene/divinylbenzene copolymer, 200-400 mesh) because of its track record in solid-phase peptide synthesis.26 Unfortunately, the Merrifield resin has limitations as a carbohydrate carrier to study interactions between the carbohydrates and relevant binding proteins. The hydrophobic nature of the resin leads to nonspecific, irreversible protein adsorption.27 Later work utilized Rapp s TentaGel, an amphiphilic, polyethylene glycol resin.28... 

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