Rapid Construction of a Tyr C6–Trp C5′ Linkage: Application in the Total Synthesis of Micitide 982, a Noncanonical Cyclic Peptide

H Hiroshige Ogawa (Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, 999077 Kowloon, Hong Kong SAR, China) Y Yuuya Nagata (Institute for Chemical Reaction Design and Discovery (WPI-ICReDD)) T Tsz Ki Chan (Department of Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong SAR, China) Y Yudai Matsuda (Department of Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong SAR, China) H Hugh Nakamura (Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, 999077 Kowloon, Hong Kong SAR, China)

Abstract

Abstract In this study, a facile synthesis method for a highly strained Tyr C6‐to‐Trp C5′ linkage was developed. This method enables the convergent introduction of arbitrary biaryls to peptide linkers through electrochemically assisted Ni‐catalyzed cross‐electrophile coupling, followed by regioselective Larock macrocyclization. Additionally, using this approach, the total synthesis of the ribosomally synthesized and post‐translationally modified peptide (RiPP) molecule micitide 982 was accomplished. Furthermore, this synthetic strategy allows for the incorporation of various biaryls.

Article Details

Volume / Issue Vol. 64, Issue 46
Published November 10, 2025
ISSN 1433-7851
Publisher Wiley

Journal Info

Angewandte Chemie International Edition

Wiley

ISSN: 1433-7851 Physical Sciences

Authors (5)

H

Hiroshige Ogawa

Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, 999077 Kowloon, Hong Kong SAR, China

Y

Yuuya Nagata

Institute for Chemical Reaction Design and Discovery (WPI-ICReDD)

T

Tsz Ki Chan

Department of Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong SAR, China

Y

Yudai Matsuda

Department of Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong SAR, China

H

Hugh Nakamura

Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, 999077 Kowloon, Hong Kong SAR, China