Thioimidate Solutions to Thioamide Problems during Thionopeptide Deprotection.

Abstract

Thioamides have structural and chemical similarity to peptide bonds, offering valuable insights when probing peptide backbone interactions, but are prone to side reactions during solid-phase peptide synthesis (SPPS). Thioimidates have been demonstrated to be effective protecting groups for thioamides during peptide elongation. We further demonstrate how thioimidates can assist thioamides through the most yield-crippling step of thionopeptide deprotection, allowing for the first isolation of an important benchmark α-helical peptide that had previously eluded synthesis and isolation.