Asymmetric macrocyclization enabled by Rh(Ⅲ)-catalyzed C-H activation:Enantioenriched macrocyclic inhibitor of Zika virus infection  

作　　者：Chao Chen Wenwen Yu Guangen Huang Xuelian Ren Xiangli Chen Yixin Li Shenggui Liang Mengmeng Xu Mingyue Zheng Yaxi Yang He Huang Wei Tang Bing Zhou 

机构地区：[1]School of Pharmaceutical Science and Technology,Hangzhou Institute for Advanced Study,University of Chinese Academy of Sciences,Hangzhou 310024,China [2]State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China [3]Shandong Laboratory of Yantai Drug Discovery,Bohai Rim Advanced Research Institute for Drug Discovery,Yantai 264117,China [4]School of Chinese Materia Medica,Nanjing University of Chinese Medicine,Nanjing 210023,China [5]State Key Laboratory of Chemical Biology,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China [6]University of Chinese Academy of Sciences,Beijing 100049,China [7]Department of Medicinal Chemistry,School of Pharmacy,Fudan University,Shanghai 201203,China

出　　处：《Chinese Chemical Letters》2024年第11期378-383,共6页中国化学快报（英文版）

基　　金：supported by National Natural Science Foundation of China(No.81973166);Science and Technology Commission of Shanghai Municipality(No.22XD1424600);Natural Science Foundation of Shanghai Municipality(No.22ZR1474100);Taishan Scholar Foundation of Shandong Province(No.tsqn202306322);National Key R&D Program of China(No.2021YFC2300700);Shandong Laboratory Program(No.SYS202205);Shandong Provincial Natural Science Foundation(Nos.ZR2023LSW003 and ZR2023JQ028)。

摘　　要：The development of enantioselective C-H macrocyclizations to efficiently access structurally diversified macrocycles is highly desirable,but remain a big challenge.Herein,we reported the first rhodium(Ⅲ)-catalyzed asymmetric intramolecular C-H macrocyclization,enabling the efficient synthesis of structurally diverse enantioenriched macrocycles.This robust enantioselective C-H macrocyclization has a broad functional group tolerance,excellent enantioselectivities(up to 98.5:1.5 e.r.)and a mild reaction condition,releasing CO_(2)as the single by-product.More significantly,the resulting unique enantioenriched19-membered macrocycle 2f was found to demonstrate a potent in vitro anti-Zika virus(ZIKV)activity without obvious cytotoxicity.Further investigation revealed that the anti-ZIKV activity is presumably attributed to an autophagy inhibition in the early stage of viral infection by down-regulating the expression of autophagy related gene Atg12.

关 键 词：C-H activation Carboamidation Enantioselective macrocyclization Anti-Zika virus activity 

分 类 号：R373[医药卫生—病原生物学] O621.251[医药卫生—基础医学]