Ag(i)-promoted fragment coupling of peptide thioamides

Abstract

Despite advances in solid phase peptide synthesis and peptide ligation, challenges remain in the assembly of polypeptides through coupling of peptide fragments. Herein we describe a new method for peptide fragment coupling employing the Ag(I)-promoted transformation of peptide thioamides. This process proceeds via an isoimide-tethered intermediate, which undergoes an O–N acyl transfer to generate the polypeptide. This method is applicable to both solution- and solid-phase coupling.