Poster Presentation International Peptide Symposium 2023

N-Glyoxylyl peptides possessing 2-oxo aldehyde unit (1) accept bioorthogonal modifications including reactions with hydoxyamine or 1,2 aminothiol to become a various type of peptides. Such a modification allows the late-stage diversification of parent N-glyoxylyl peptides^{Ref. 1}. Oxdative cleavage of N-terminal serine residue represents the chemical methodology for preparing N-glyoxylyl peptides^{Ref. 2} but induces side reactions on oxidation-sensitive residues. In this context, oxidant-free access has been desired.

We recently found that a thioester induces N-terminal glycyl α-hydroxamic acid (Gly(α-HA)) (2) to convert to N-glyoxylyl peptide 1 in an oxidant-free manner. The conversion proceeds through the chemoselective O-acylation of the hydroxamic unit followed by Lossen rearrangement allowing the intramolecular transfer of oxidation state from the hydroxamic moiety to α-carbon. Encouraged by the above preliminary result, we optimized the conditions for the intramolecular redox conversion of the Gly(α-HA) to glyoxylyl residues. Additionally, selective modification of the resulting glyoxylyl unit was investigated. Consequently, Boc₂O was proved to be an ideal acylating agent where no significant side reaction was observed. Moreover, we accomplished further conversion of glyoxylyl unit such as Mannich type reaction and one-pot oxime/hydrazone ligation. These conversions enable peptide ligation and cyclization for diversification of N-glyoxylyl peptide.