Reaction of α-amino esters and α-amino ester imines with thiiranium ion intermediates. Application to the synthesis of new potential aminopeptidase inhibitors and mechanistic implications

Abstract

Imines derived from α-amino esters react with thiiranium ions generated in situ from 2,3-epoxy sulfides, to give an iminium ion which can be readily hydrolysed by aqueous base to liberate a secondary amine, the product of selective monoalkylation of the primary amino group. Overall yields for this process are only moderate, but can be improved by use of α-amino esters themselves as nucleophiles at low temperature. Interesting reactivity profiles of the thiiranium ion intermediates are observed, and consequent implications for the nature of the reactive intermediates involved are discussed. The products obtained from these reactions are model systems for the synthesis of compounds related to α-thiolbestatin and other known potent aminopeptidase inhibitors.