Efficient synthesis of a bacterial translocase MraY inhibitor

Abstract

The bacterial translocase MraY has recently been demonstrated as a prime target for the development of new antibiotics. We describe a straightforward synthesis of a new inhibitor 1 of this enzyme. The two key steps involve a tandem nucleophilic epoxide ring opening of C2-symmetrical bis-epoxide and subsequent O-heterocyclisation, followed by O-glycosylation. The in vitro biological evaluation of 1 at 2 mM showed an 81% of inhibition of the MraY activity. Therefore, congeners of 1 should permit detailed SAR investigations for the discovery of novel antibacterials.