Ring closing metathesis of α- and β- amino acid derived dienes

Abstract

Three new classes of conformationally constrained peptidomimetics, derived from modified α- and β-amino acids, have been prepared by ring closing metathesis (RCM). The first involves Cα-N′ cyclisation of the peptidic diene (23, 24, 26), the second Cβ2-N′ cyclisation (27, 28, 29), and the third N-Cβ2 cyclisation (30). The key C-centred olefin of the dienes was introduced by stereoselective α-allylation of either an α- or β-amino acid. The normal favourable influence of a tertiary amide linker in the diene towards RCM is negated by significant steric congestion, and the combination of a secondary amide linker and α,α-disubstitution promotes ring contraction on RCM. © 2006 Elsevier B.V. All rights reserved.