C‐Terminal Bioconjugation of Peptides through Photoredox Catalyzed Decarboxylative Alkynylation

• Published in: Angewandte Chemie International Edition Vol. 58; no. 24; pp. 8182 - 8186
• Main Authors: Garreau, Marion, Le Vaillant, Franck, Waser, Jerome
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 11-06-2019
• Edition: International ed. in English
• Subjects: Amino acids; Carboxylic acids; Functional groups; hypervalent iodine; Iodine; late-stage functionalization; organic dyes; Oxidation; Peptides; photoredox catalysis; Reagents; Selectivity; hypervalent iodine; peptides; organic dyes; photoredox catalysis; late-stage functionalization
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201901922

We report the first decarboxylative alkynylation of the C‐terminus of peptides starting from free carboxylic acids. The reaction is fast, metal‐free, and proceeds cleanly to afford alkynylated peptides with a broad tolerance for the C‐terminal amino acid. By the use of hypervalent iodine reagents, the introduction of a broad range of functional groups was successful. C‐terminal selectivity was achieved by differentiation of the oxidation potentials of the carboxylic acids based on the use of fine‐tuned organic dyes.
Only at the end: A decarboxylative alkynylation of the C‐terminal of peptides starting from free carboxylic acids has been developed. The reaction is fast, metal‐free, and proceeds cleanly to afford alkynylated peptides bearing a broad range of functional groups. C‐terminal selectivity was achieved based on the use of fine‐tuned organic dyes.