Constrained Glu‐Gly and Gln‐Gly dipeptide surrogates from γ‐substituted α‐amino‐δ‐lactam synthesis

Abstract

Conformationally rigid α‐amino‐δ‐lactam surrogates of Glu‐Gly and Gln‐Gly dipeptides have been synthesized from α‐amino‐γ‐vinyl‐δ‐lactam precursors. A reductive cyclization protocol from the respective (4R)‐ and (4S)‐2‐N‐(Boc)amino‐4‐(azidomethyl)hexenoates gave δ‐lactams, which were converted to the corresponding dipeptide surrogates by N‐alkylation with methyl bromoacetate. The utility of these α‐amino‐γ‐vinyl‐δ‐lactam building blocks was demonstrated by olefin oxidation and peptide coupling to prepare constrained Glu and Gln residues.