Rh(Ⅲ)-catalyzed late-stage C-H alkenylation and macrolactamization for the synthesis of cyclic peptides with unique Trp(C7)-alkene crosslinks  

作　　者：Shulei Hu Yu Zhang Xiong Xie Luhan Li Kaixian Chen Hong Liu Jiang Wang 

机构地区：[1]Department of Medicinal Chemistry,School of Pharmacy,China Pharmaceutical University,Nanjing 211198,China [2]State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China [3]Lingang Laboratoty,Shanghai 200031,China [4]School of Life Science and Technology,ShanghaiTech University,Shanghai 200031,China

出　　处：《Chinese Chemical Letters》2024年第8期270-277,共8页中国化学快报（英文版）

基　　金：the National Key R&D Program of China(No.2022YFA1302900 to H.Liu);National Natural Science Foundation of China(Nos.82130105,22337003,82121005 to H.Liu;and Nos.22177124,82322063 to J.Wang);Program of Shang-hai Academic Research Leader(No.23XD1460300 to J.Wang);the Lingang Laboratory(No.LG-GG-202204-02 to J.Wang)for supporting this work.We would like to acknowledge Shanghai Highline Therapeutics.

摘　　要：Heterocycle-braced cyclic peptides have demonstrated enhanced metabolic stability,increased potency and selectivity.Here,we present a rapid synthesis method for constructing Trp(C7)-alkene(E)-crosslinked cyclic peptides with potent anti-proliferative activities against cancer cells,through C-H alkenylation and macrolactamization.This report addresses critical challenges associated with the installation and removal of the directing group N-Piv,configuration selectivity of the olefin,and intramolecular cyclization.No-tably,this method exhibits mild reaction conditions,traceless removal of the directing group,and high configuration selectivity.

关 键 词：C-H functionalization Rh(Ⅲ)-catalyzed ALKENYLATION Cyclic peptides MACROLACTAMIZATION 

分 类 号：O629.72[理学—有机化学]