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Updated: Nov 1, 2025

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
Streamlined construction of peptide macrocycles via palladium-catalyzed intramolecular S-arylation in solution and on
Peng Yang1, Xuan Wang2, Bo Li1
1State Key Laboratory and Institute of Elemento-Organic Chemistry, College of Chemistry, Nankai University Tianjin 300071 China hegang@nankai.edu.cn gongchen@nankai.edu.cn.
Abstract:
A highly efficient and versatile method for construction of peptide macrocycles via palladium-catalyzed intramolecular S-arylation of alkyl and aryl thiols with aryl iodides under mild conditions is developed. The method exhibits a broad substrate scope for thiols, aryl iodides and amino acid units. Peptide macrocycles of a wide range of size and composition can be readily assembled in high yield from various easily accessible building blocks. This method has been successfully employed to prepare an 8-million-membered tetrameric cyclic peptide DNA-encoded library (DEL). Preliminary screening of the DEL library against protein p300 identified compounds with single digit micromolar inhibition activity.
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