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Radical‐Mediated Acyl Thiol‐Ene Reaction for Rapid Synthesis of Biomolecular Thioester Derivatives
Author(s) -
McLean Joshua T.,
Milbeo Pierre,
Lynch Dylan M.,
McSweeney Lauren,
Scanlan Eoin M.
Publication year - 2021
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.202100615
Subject(s) - native chemical ligation , chemistry , bioconjugation , thioester , thiol , ene reaction , combinatorial chemistry , chemical synthesis , chemical ligation , click chemistry , cysteine , organic chemistry , chemical biology , sulfur , amino acid , biochemistry , in vitro , enzyme
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.