2-Oxothiazolidine-4-carboxylic acid and related substances

Abstract

Two techniques proposed for specific cleavage of the N-acyl cysteinyl bond in peptides involve the formation of 2-oxothiazolidine-4-carboxyl residues (I; Z = 0) and 2-iminothiazolidine-4-carboxyl residues (I; Z = NH), as the new N-terminal groups. The corresponding acids ((11) and (IV) respectively) have been synthesized and their behaviour to hydrolysis and to oxidation has been studied. Whereas (11) was decomposed by vigorous acid hydrolysis, (IV) was stable. Oxidation of (11) gave cysteic acid, whilst (IV) gave N-carbamidocysteic acid, and both of these oxidation products offer potential methods for estimating the extent of the specific cleavage. The S-phenylthiocarbonyl and S-4-nitrophenyloxycarbonyl derivatives of N-acetylcysteine (111; R = PhS or p-NO2C6H4O) form (11) under mild alkaline conditions, and hence the proposed cleavage mechanism is supported.