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

Autor(es)

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

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: CHEM; v. 6, n. 12, p. 3428-3439, DEC 3 2020.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 18/14595-0 - Aplicação da Fotocatálise na Modificação e Funcionalização Assimétrica de Peptídeos
• Beneficiário: Rafaely Nascimento Lima
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado