Peptide thioamides: exploiting a single-atom substitution

Abstract

Peptide thioamides, in which a single backbone oxygen atom is replaced by sulfur, display markedly altered structural, spectroscopic and reactive properties relative to native amides. This personal perspective highlights our group’s exploration of the unique reactivity of peptide thioamides and the development of AgI-promoted transformations that exploit this subtle but powerful single-atom substitution. Initial studies demonstrated that thioamides undergo silver-mediated coupling with carboxylates to generate reactive isoimide intermediates that can then undergo 1,3-acyl transfer to generate imides, or be intercepted by appropriately reactive and positioned nucleophiles. This mechanistic pl..