Abstract
TBAJ-587, an analogue of the antituberculosis drug bedaquiline (BDQ), bearing a diarylquinoline skeleton retains the high bacterial potency, is less toxic, and has a better pharmacokinetic profile than the parent molecule, which has entered phase I clinical trials. In contrast to its fascinating bioactivity, however, the highly efficient synthesis of this molecule is still an unsolved challenge. Herein, the first asymmetric synthesis of TBAJ-587 based on a synergistic Li/Li bimetallic system is reported. The product could be obtained in an excellent yield of 90% and an enantiomeric ratio (er) of 80:20. Furthermore, the reaction could be conducted on a 5 g scale, and the product was obtained with 99.9:0.1 er after a simple recrystallization. The realization of this protocol will greatly aid the demand for clinical drug production.