Peptide cyclization viaring-closing metathesis: the N-alkenoxy peptide approach

Abstract

The preparation of cyclic hexapeptides from N-hydroxy tripeptides building blocks is described. Introduction of an unsaturated chain on the hydroxamate oxygen followed by fragment coupling leads to N,N′-dialkenoxy hexapeptides that are efficiently cyclized through a ring-closing metathesis reaction. The length of the alkene chains allows the modulation of the ring size: the synthesis of 17- and 18-membered cycles is reported.