Asymmetric Synthesis of Anti-tuberculosis-specific Drug TBAJ-876 through Synergistic Li/Li Catalysis  

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

机构地区：[1]Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs,School of Pharmacy,Shanghai Jiao Tong University,800 Dongchuan Road,Shanghai,200240 China [2]Frontiers Science Centre for Transformative Molecules,School of Chemistry and Chemical Engineering,Shanghai Jiao Tong University,Shanghai,200240 China

出　　处：《Chinese Journal of Chemistry》2023年第11期1319-1326,共8页中国化学（英文版）

基　　金：funding support of this work by the Bill and Melinda Gates Foundation(No.INV-008413);the National Natural Science Foundation of China(No.21831005)and Shanghai Jiao Tong University.

摘　　要：TBAJ-876, developed by TB Alliance, a novel anti-tuberculosis-specific drug, has entered Phase II clinical trials. Herein, the first asymmetric synthesis of TBAJ-876 has been realized using synergistic Li/Li catalysis with excellent yield of 95% and 88 : 12 er (99.6 : 0.4 er, 10 : 1 dr after simple recrystallization). Furthermore, DFT calculations and 7Li-NMR analysis illustrated the mechanism of the synergistic reaction: a chiral Li-complex activates the nucleophile to control the stereoselectivity, while the other achiral Li-complex activates the electrophile to catalyze the carbonyl addition reaction. Additionally, this protocol has been successfully carried out at 5 gram-scale, showing its industrial potential.

关 键 词：Asymmetric synthesis TBAJ-876 Synergistic Li Li catalysis DFT calculations Noncovalent interactions Coordination modes LITHIUM ENANTIOSELECTIVITY 

分 类 号：O62[理学—有机化学]