Catalytic enantioselective total synthesis of antitubercular agents (-)-bedaquiline and (-)-sudapyridine enabled by dynamic kinetic resolution-asymmetric transfer hydrogenation.

ABSTRACT: (-)-Bedaquiline [(-)-BDQ] is considered to be one of the most promising new therapeutic agents for tuberculosis for over 50 years. However, there are limited general and highly stereocontrolled asymmetric synthetic methods available for (-)-BDQ and its analogues due to the challenge of forging their vicinal stereocenters. Herein, we report a concise and stereocontrolled synthetic route to (-)-BDQ in six steps with an overall yield of 34%, integrating a Rh-catalyzed dynamic kinetic resolution-asymmetric transfer hydrogenation (DKR-ATH) with TADDOL-mediated diastereoselective allylation. The reactivity and stereoselectivity of DKR-ATH were systematically investigated using a range of sterically hindered N-hetero-1,2,2-triarylethanones. This approach offers a robust and reliable method

SUBMITTER: Han J 

PROVIDER: S-EPMC12224407 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature