Oxidative peptide bond formation of glycine–amino acid using 2-(aminomethyl)malononitrile as a glycine unit

Abstract

Amide linkage of glycine–amino acid was synthesized by coupling of substituted 2-(aminomethyl)malononitrile as a C-terminal glycine unit and N-terminal amine using CsOAc and O₂ in an aqueous solution. This is a coupling reagent-free and catalyst-free peptide synthesis via oxidative amide bond formation. Various tripeptides and tetrapeptides were synthesized efficiently and the sulfide moiety is inert even under an oxygen atmosphere.