Development of oxidant free methodology for preparing N-glyoxylyl peptide and its apprications — ASN Events

Development of oxidant free methodology for preparing N-glyoxylyl peptide and its apprications (#248)

Junya Hayashi 1 , Daishiro Kobayashi 1 , Masaya Denda 1 , Akira Otaka 1
  1. Tokushima University, Shomachi, TOKUSHIMA, Japan

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 peptidesRef. 1. Oxdative cleavage of N-terminal serine residue represents the chemical methodology for preparing N-glyoxylyl peptidesRef. 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.64f0314eb6e48-IPS_Abstract_Junya_Hayashi.png

  1. O. El-Mahdi, O. Melnyk, Bioconjugate. Chem., 2013, 24, 735-765.
  2. T. Kawakami, K. Akaji, S. Aimoto, Org Lett., 2001, 3, 1403-1405.
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