Emma Yates ’11
Direct Approach to the Functionalized Propellane Core of Pleuromutilin, Towards Possible New Antibiotics Against Tuberculosis
Pleuromutilin is a natural product with antibiotic activity against tuberculosis, but that has never been approved for human oral administration because of poor pharmacokinetic properties. We have been synthesizing the first pleuromutilin derivatives that include changes to the architectually novel propellane core of the molecule, in hopes of creating analogs with improved activity and metabolic stability sufficient to allow them to be explored from a clinical perspective. This summer I worked on optimizing our route towards our key intermediate compound and developed a novel in situ silyation protocol which appears to be generally applicable in the stoichiometric Nozaki-Hiyama-Kishi reaction. Though an adaption of this protocol we are now able to gain access to enantiopure material, and work continues in our laboratory towards synthesizing and testing racemic and enantiopure pleuromutilin derivatives.
Princeton University, Princeton, NJ