Stereoselective chain elongation at C-3 of cysteine through 2,3-dihydrothiazoles, without racemization. Preparation of 2-amino-5-hydroxy-3-mercaptoalkanoic acid derivatives

Abstract

The enantio pure thiazolines 1–3 have been prepared from cysteine; detailed procedures for the dimethyl ester 3 are described (intermediates 4–6). Addition of a cuprate (to give 7), of Danishefski's diene (to give 8) and of enamines (to give 10a–13a,14) to the thiazoline double bond are highly diastereoselective (single isomers of 10a–13a are obtained). The keto-alkylated products 10a–13a are reduced to 5-(β-hydroxyalkyl)thiazolidinedicarboxylates 10b–13b(or the epimers 10c and 13c). The configurations at the up to three new stereogenic centres have been assigned by NMR spectroscopy (cf. the bicyclic lactones 10d and 10e). In one case, a free α-amino-β-mercapto-δ-hydroxy carboxylic acid was prepared (15). The overall process constitutes a stereoselective replacement of H^Re at C-3 in L- or (R)-cysteine by a chain of carbon atoms, the key step being a Michael addition to an enantiopure 2,3-dehydrocysteine derivative 3.