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.