Unveiling p-quinone methide (QM) chemistry to synthesize bedaquiline (TMC 207) like architectures

摘要

Bedaquiline (TMC 207) is the first FDA-approved drug to combat multidrug-resistant (MDR) tuberculosis. Herein, we disclosed hydroacylation (tandem C-H activation/C-C bond formation/aromatization) catalyzed by Wilkinson catalyst on quinoline containing new para-quinone methides to simplify the construction of diverse bedaquiline analogs with reduction of steps. Direct installation of three crucial aryl rings in hydroacylation giving rise to alpha-disubstituted aryl ketone can provide a series of bedaquiline analogs. (C) 2021 Elsevier B.V. All rights reserved.