Chlorination at the 8-Position of a Functionalized Quinolone and the Synthesis of Quinolone Antibiotic ABT-492

Abstract

The total synthesis of quinolone antibiotic ABT-492 has been achieved in 67% yield over nine steps from 2,4,5-trifluorobenzoic acid. The highlights of this synthesis include a novel chemoselective chlorination at the 8-position of a highly elaborated quinolone core. In addition, a Lewis acid promoted cyclization reaction to form the quinolone heterocycle was developed which was incorporated into a one-pot, three-step cyclization/coupling/protection sequence that proceeds in 93% yield.