A modular and enantioselective synthesis of the pleuromutilin antibiotics

A route to pleuromutilin compounds facilitates targeted stereochemical variation for optimization of antibiotic properties.
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.

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