Polymeric reagents synthesis

A technique of peptide synthesis different from Merrifield s method has been introduced (Fridkin et aL, 1965a, 1965b, 1966 Wieland and Birr, 1966a, 1966b). This method is based on the use of polymer-supported amino acid active esters. Wunsch (1971) refers to this technique as polymeric reagent synthesis. The method is claimed to be free from certain limitations of the classical solid-phase peptide synthesis e.g., it offers the advantage of isolation and purification of the intermediate peptides, and the synthesis does not go unchecked. However, the method has certain limitations. These will be discussed later. 

The structures of these ylide polymers were determined and confirmed by IR and NMR spectra. These were the first stable sulfonium ylide polymers reported in the literature. They are very important for such industrial uses as ion-exchange resins, polymer supports, peptide synthesis, polymeric reagent, and polyelectrolytes. Also in 1977, Hass and Moreau [60] found that when poly(4-vinylpyridine) was quaternized with bromomalonamide, two polymeric quaternary salts resulted. These polyelectrolyte products were subjected to thermal decyana-tion at 7200°C to give isocyanic acid or its isomer, cyanic acid. The addition of base to the solution of polyelectro-lyte in water gave a yellow polymeric ylide. 

Under certain condition, however, reactions are still preferably conducted in solution. This is the case e.g., for heterogeneous reactions and for conversions, which deliver complex product mixtures. In the latter case, further conversion of this mixture on the solid support is not desirable. In these instances, the combination of solution chemistry with polymer-assisted conversions can be an advantageous solution. Polymer-assisted synthesis in solution employs the polymer matrix either as a scavenger or for polymeric reagents. In both cases the virtues of solution phase and solid supported chemistry are ideally combined allowing for the preparation of pure products by filtration of the reactive resin. If several reactive polymers are used sequentially, multi-step syntheses can be conducted in a polymer-supported manner in solution as well. As a further advantage, many reactive polymers can be recycled for multiple use. 

Reactions on macromolecular precursors are most often the key step in the synthesis of sophisticated polymers in various well documented fields of steadily increasing importance such as a) linear or crosslinked polymeric reagents and catalysts (2,5,6, 49) b) polymers showing esterolytic enzyme-like properties (2, 49-52) c) polymeric drugs (53.54) and so on... Three more specific but still highly significant studies are outlined below. 

The versatility of polymerization resides not only in the different types of reactants which can be polymerized but also in the variations allowed by copolymerization and stereoselective polymerization. Chain copolymerization is the most important kind of copolymerization and is considered separately in Chap. 6. Other copolymerizations are discussed in the appropriate chapters. Chapter 8 describes the stereochemistry of polymerization with emphasis on the synthesis of polymers with stereoregular structures by the appropriate choice of initiators and polymerization conditions. In the last chapter, there is a discussion of the reactions of polymers that are useful for modifying or synthesizing new polymer structures and the use of polymeric reagents, substrates, and catalysts. The literature has been covered through early 2003. 

Polymeric phosphonium salt-bound carboxylate, benzenesulphinate and phenoxide anions have been used in nucleophilic substitution reactions for the synthesis of carboxylic acid esters, sulphones and C/O alkylation of phenols from alkyl halides. The polymeric reagent seems to increase the nucleophilicity of the anions376 and the yields are higher than those for corresponding polymer phase-transfer catalysis (reaction 273). 

Kumari, K. A. Sreekumar, K. Polymeric Acyl Transfer Reagents Synthesis of Amides Using Polystyrene Supported Oximino Esters, Polymer 1996,37, 171. 

Parlow, J. J. Simultaneous Multistep Synthesis Using Polymeric Reagents, Tetrahedron Lett. 1995, 36, 1395. 

N. M. Weinshenker, G. A. Crosby, and J. Y. Wong, Polymeric Reagents. IV. Synthesis and utilization of an insoluble polymeric organotin dihydride reagent, J. Org. Chenx. 40 1966 (1975). 

The use of polymeric reagents or catalysts is popular in organic synthesis. Usually, the reactive entity is attached to a solid support, and while its chemical properties are similar to its solution counterpart, the heterogeneicity of the solid supported version... 

Since the introduction of sohd-phase peptide synthesis (SPPS) on lightly crosslinked polystyrene (PSty) by Merrifield in 1962,this technique has been optimized in all its aspects and has subsequently found widespread application in many other fields of organic chemistry, e.g. for the synthesis of oligonucleotides, for catalysis, for the immobilization of enzymes in biotechnology, and for the preparation of polymeric reagents. A new but very rapidly growing field of application of this revolutionary method is the use of solid-phase techniques in combinatorial chemistry for the synthesis of hbraries of compounds whose constituents differ widely in their chemical nature. ... 

Most of the polymeric reagents which have been developed so far make use of an insoluble cross-linked polymer as the backbone. Investigations on the reaction rates and kinetic course in solid-phase synthesis revealed that the reaction sites within the polymeric matrix are chemically and kinetically not equivalent, making quantitative conversions almost impossible. Furthermore, the difficulty in the preparation and accessibility of insoluble polymeric reagents appears to limit a more... 

Weinshenker, N. M., Shen, C. M. Polymeric reagents. I. Synthesis of an insoluble polymeric carbodiimide. Tetrahedron Lett. 1972, 3281-3284. 

JJ Parlow. Simultaneous multistep synthesis using polymeric reagents. Tetrahedron Lett 36 1395-1396, 1995. 

Polymeric Reagents in Organic Synthesis Ned M. Weinshenker, Guy A. Crosby 11. 281 ... 

N.M. Weinshenker and C.M. Shen. Polymeric reagents. 1. Synthesis of an insoluble carbodiimide. Tetrahedron Lett., (1972) 3285. 

Scheme 3.12 illustrates the polymer-supported aUylboron reagents derived from chiral N-sulfonylamino alcohols and used for the asymmetric synthesis of homoal-lylic alcohols and amines (see Scheme 3.12) ]29]. All of these asymmetric allylbora-tions were performed using the polymeric chiral aUylboron reagent prepared from triallylborane and PS-supported N-sulfonylamino alcohols 38-41. High levels of enantioselectivity were obtained in the asymmetric allylboration of imines with the polymeric reagent derived from norephedrine.

Konigs-Knorr synthesis (1, 1005 4, 67). The Konigs-Knorr synthesis of )3-glucosides is improved with respect to reaction conditions and to yield by use of silver salts of dicarboxylic acids e.g., oxalic acid) or of hydroxy carboxylic acids (e.g., 4-hydroxyvaleric acid). Use of the silver salt of a polymeric reagent offers the further advantages of other polymeric reagents. ... 

Fig. 13. Examides of polymeric reagents useful fn- peptide synthesis by invert solid phase method (see Fig. 16)...

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