Synthesis of Peptide N-Acylpyrroles via Anodically Generated N,O-Acetals

Abstract

AbstractAn electrochemical approach to peptide C-terminal N-acylpyrroles is described from readily accessible C-terminal hydroxyproline-containing peptides, prepared via standard Fmoc solid-phase peptide synthesis (Fmoc-SPPS). Following electrochemical decarboxylation, the reactive hydroxyproline-derived N,O-acetal intermediate is aromatized under mild acidic conditions, which enable concomitant deprotection of amino acid side-chain protecting groups. The resulting peptide N-acylpyrrole is amenable to late-stage peptide modifications, including reduction with NaBH4 to deliver a valuable C-terminal peptide aldehyde motif.