Peptide Late-Stage Diversifications by Rhodium-Catalyzed Tryptophan C7 Amidation

Author(s)

Wang, Wei ^[1] ; Wu, Jun ^[1] ; Kuniyil, Rositha ^[1] ; Kopp, Adelina ^[1] ; Lima, Rafaely Nascimento ^[1] ; Ackermann, Lutz ^{[1, 2]}

Affiliation

^[1] Georg August Univ Gottingen, Inst Organ & Biomol Chem, Tammannstr 2, D-37077 Gottingen - Germany

^[2] DZHK German Ctr Cardiovasc Res, Potsdamer Str 58, D-10785 Berlin - Germany

• Document type: Journal article
• Source: CHEM; v. 6, n. 12, p. 3428-3439, DEC 3 2020.
• Web of Science Citations: 0

Abstract

The late-stage diversification (LSD) of structurally complex peptides has emerged as a powerful platform for molecular engineering and drug discovery. Besides traditional peptide modifications, such as native chemical ligations or cross-couplings with prefunctionalized substrates, during recent years, C-H activation has gained considerable momentum as a robust and step-economical strategy for latestage peptide modifications, thus far predominantly for the formation of C-C bonds. Although C-N bond formations represent established strategies in medicinal chemistry and drug discovery, methods for direct amidations of tryptophan and tryptophan-containing peptides are rare and severely limited to the activated C2 position. In contrast, we herein disclose the first example of direct late-stage peptide C-H amidation reaction and the unprecedented late-stage peptide diversification on tryptophan C7 position in a highly site-selective manner. Moreover, this strategy sets the stage for sequential double C(7)-H/C(2)-H modifications, further improving the peptide structural complexity. (AU)

• FAPESP's process: 18/14595-0 - Application of Photocatalysis in Modification and Asymmetric Functionalization of Peptides
• Grantee: Rafaely Nascimento Lima
• Support Opportunities: Scholarships in Brazil - Post-Doctoral