Streamlined construction of peptide macrocycles via palladium-catalyzed intramolecular S -arylation in solution and on DNA

作者：Peng Yang, Xuan Wang, Bo Li, Yixuan Yang, Jinfeng Yue, Yanrui Suo, Huarong Tong, Gang He, Xiaojie Lu, Gong Chen · 发表于：Chemical Science · 年份：2021 · DOI：10.1039/d1sc00789k · 被引用次数：64 · 研究领域：Sulfur-Based Synthesis Techniques、Chemical Synthesis and Analysis、Click Chemistry and Applications

-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.