Stereoretentive Synthesis and Chemoselective Amide-Forming Ligations of C-Terminal Peptide α-Ketoacids

Abstract

C-Terminal peptide cyanosulfur ylides are readily converted to C-terminal peptide alpha-ketoacids, poised for chemoselective amide-forming reactions with hydroxylamines. These easily prepared and bench stable ylides are quickly and selectively oxidized with aqueous Oxone without the need for protection of most peptide side chains and with minimal epimerization. This approach offers the first method for preparing enantiomerically enriched, side chain unprotected alpha-ketoacids.