Asymmetric synthesis of bedaquiline based on bimetallic activation and non-covalent interaction promotion strategies  被引量:1

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作  者:Feng Gao Jing Li Tanveer Ahmad Yicong Luo Zhenfeng Zhang Qianjia Yuan Xiaohong Huo Tao Song Wanbin Zhang 

机构地区:[1]Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs,Frontiers Science Center for Transformative Molecules,School of Chemistry and Chemical Engineering,Shanghai Jiao Tong University,Shanghai 200240,China [2]School of Pharmacy,Shanghai Jiao Tong University,Shanghai 200240,China

出  处:《Science China Chemistry》2022年第10期1968-1977,共10页中国科学(化学英文版)

基  金:supported by the Bill and Melinda Gates Foundation (INV-008413);the National Natural Science Foundation of China (21831005);Shanghai Jiao Tong University

摘  要:Bedaquiline(BDQ),approved by Food and Drug Administration(FDA)in 2012 as the first anti-tuberculosis-specific drug in the last 40 years,is viewed as one of the world’s most promising treatments for tuberculosis(TB).Due to the stereoselective construction of the Csp^(3)–Csp^(3)bond with vicinal stereocenters of BDQ and its analogues being an unsolved challenge,there have not been any reports concerning its asymmetric synthesis for the current industrial production process until now.Herein,we have successfully developed a cooperative bimetallic system for the asymmetric synthesis of BDQ under the guidance of density functional theory(DFT)computations.Based on the optimized conditions,BDQ could be synthesized with excellent enantioselectivity(>99%ee)and diastereoselectivity(16:1 dr).A 5-g scale reaction was also conducted with comparably excellent results,showing its potential for industrial application.

关 键 词:asymmetric synthesis bedaquiline bimetallic system industrial synthetic process DFT computation 

分 类 号:TQ460.1[化学工程—制药化工]

 

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