Fmoc Solid‐Phase Synthesis of C‐Terminal Peptide Thioesters by Formation of a Backbone Pyroglutamyl Imide Moiety

Abstract

Activating an inactive bond: A new concept in synthetic peptide chemistry, backbone amide activation, proceeds through the selective conversion of a backbone amide into an imide, followed by nucleophilic acyl displacement (see scheme; Boc=tert-butoxycarbonyl, Pg=protecting group). This methodology represents a new approach to solid-phase synthesis of C-terminal peptide thioesters, and may become a general tool for the synthesis of peptide thioesters.