A modular and enantioselective synthesis of the pleuromutilin antibiotics

Abstract

A versatile synthesis of pleuromutilin Synthetic flexibility is crucial for antibiotic development, because numerous subtle structural variations can contribute to combating resistant strains. A derivative of the fungal natural product pleuromutilin was approved a decade ago for treatment of Gram-positive bacterial skin infections; recent efforts to tune the structure for activity against Gram-negative bacteria have focused on the stereochemistry at a particular carbon center. Murphy et al . present a synthetic route to pleuromutilin that allows the configurations in that segment of the molecule to be varied, offering a distinct path for structural optimization. Science , this issue p. 956