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

Chao Chen ¹Wenwen Yu ²Guangen Huang ³Xuelian Ren ⁴Xiangli Chen ³Yixin Li ⁵Shenggui Liang ⁵Mengmeng Xu ³Mingyue Zheng ⁶Yaxi Yang ⁷He Huang ⁸Wei Tang ⁹Bing Zhou¹⁰

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作者信息

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

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 con-dition,releasing CO2 as the single by-product.More significantly,the resulting unique enantioenriched 19-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 at-tributed to an autophagy inhibition in the early stage of viral infection by down-regulating the expression of autophagy related gene Atg12.

Key words

C-H activation/Carboamidation/Enantioselective macrocyclization/Anti-Zika virus activity

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出版年

2024

中国化学快报(英文版)

中国化学会

中国化学快报(英文版)

CSTPCDCSCD

影响因子：0.771

ISSN：1001-8417

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