Radical-Mediated Acyl Thiol-Ene Reaction for Rapid Synthesis of Biomolecular Thioester Derivatives

Joshua T. McLean, Pierre Milbeo, Dylan M. Lynch, Lauren McSweeney, Eoin M. Scanlan

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

The thiol-ene ‘click’ reaction has emerged as a versatile process for carbon–sulfur bond formation with widespread applications in chemical biology, medicinal chemistry and materials science. Thioesters are key intermediates in a wide range of synthetic and biological processes and efficient methods for their synthesis are of considerable interest. Herein, we report the first examples of acyl-thiol-ene (ATE) for the synthesis of biomolecular thioesters, including peptide, lipid and carbohydrate derivatives. A key finding is the profound effect of the amino acid side chain on the outcome of the ATE reaction. Furthermore, radical generated thioesters underwent efficient S-to-N acyl transfer and desulfurisation to furnish ‘sulfur-free’ ligation products in an overall amidation process with diverse applications for chemical ligation and bioconjugation.

Original languageEnglish
Pages (from-to)4148-4160
Number of pages13
JournalEuropean Journal of Organic Chemistry
Volume2021
Issue number29
Early online date26 Jul 2021
DOIs
Publication statusPublished - 6 Aug 2021

Keywords

  • Amides
  • Click Chemistry
  • Hydrothiolation
  • Radical Reactions
  • Thiol-ene

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry

Fingerprint

Dive into the research topics of 'Radical-Mediated Acyl Thiol-Ene Reaction for Rapid Synthesis of Biomolecular Thioester Derivatives'. Together they form a unique fingerprint.

Cite this