Synthesis of amides and peptides using polymer-bound mixed carboxylic dithiocarbamic anhydrides

Abstract

The use of polymer-bound mixed carboxylic dithiocarbamic anhydrides in the synthesis of amides and peptides is illustrated. The introduction of acetyl, benzoyl and p-nitrobenzoyl and N-protected amino acyl groups into the polymer system, and acylation and peptide synthesis reactions using these polymeric acyl transfer reagents are described. Polystyrene crosslinked with hydrophilic tetraethyleneglycol diacrylate was chosen as the support for the preparation of the polymeric reagent. The reagent was prepared by a series of polymer-analogous reactions. Polystyrene resin was functionalized to aminomethyl polystyrene. The aminomethyl resin on treatment with carbondisulphide and sodium hydroxide resulted in polystyrene-supported sodium dithiocarbamate which on reaction with an acid chloride afforded the polymer-bound mixed carboxylic dithiocarbamic anhydride. The reagent on treatment with an amine or amino acid transfers its acyl group, forming the corresponding amide or peptide. In the case of acid-sensitive amino acids and amino acids containing acid-cleavable protecting groups, mixed amino acyl dithiocarbamic anhydride resins were prepared by treating sodium dithiocarbamate resin with the anhydride of the amino acid.