Chemoselective Late-Stage Functionalization of Peptides via Photocatalytic C2-Alkylation of Tryptophan

Lee, Joanna C.; Cuthbertson, James D.; Mitchell, Nicholas J.

Abstract

Across eukaryotic proteomes, tryptophan is the least abundant of the 20 canonical amino acids, which makes it an ideal chemical handle for the late-stage functionalization of peptide and protein scaffolds with minimal production of undesired isoforms. Herein, we report the photocatalytic C2-alkylation of tryptophan using bromodifluoroacetate/acetamide-derived radical precursors. This rapid visible-light-mediated reaction is additive-free, operationally simple, and tolerates diverse functionality. We demonstrate the late-stage modification of a variety of complex peptides, including examples of biological significance.

Citation

Lee, J. C., Cuthbertson, J. D., & Mitchell, N. J. (2023). Chemoselective Late-Stage Functionalization of Peptides via Photocatalytic C2-Alkylation of Tryptophan. Organic Letters, 25(29), 5459-5464. https://doi.org/10.1021/acs.orglett.3c01795

• Journal Article Type: Article
• Acceptance Date: Jul 12, 2023
• Online Publication Date: Jul 18, 2023
• Publication Date: Jul 28, 2023
• Deposit Date: Jul 14, 2023
• Publicly Available Date: Jul 19, 2023
• Journal: Organic Letters
• Print ISSN: 1523-7060
• Electronic ISSN: 1523-7052
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 25
• Issue: 29
• Pages: 5459-5464
• DOI: https://doi.org/10.1021/acs.orglett.3c01795
• Keywords: Chemical reactions, Functionalization, Monomers, Peptides and proteins, Precursors
• Public URL: https://nottingham-repository.worktribe.com/output/23002662
• Publisher URL: https://pubs.acs.org/doi/10.1021/acs.orglett.3c01795