Designer Lantibiotics: Engineering the C-D-E Ring System of the Microbisporicins

Louisiana State University, Baton Rouge LA

Investigators

Abstract

Abstract In this project funded by the Chemical Synthesis program of the Chemistry Division, Professor Carol M. Taylor of Louisiana State University is developing approaches to the microbisporicins, a family of potent antibiotics with considerable therapeutic potential. As these compounds are entering clinical trials, the research addresses the issue of producing large quantities of lantibiotic drugs and providing unambiguous details of their structure. As an educator, Professor Taylor is producing a compendium of experimental demonstrations for use in large introductory organic chemistry classes. These lecture demonstrations illustrate important organic chemistry concepts that facilitate understanding. The studies on the synthesis of the microbisporicins embrace a number of strategies that capitalize on the sulfur-rich nature of these compounds. Specifically, the issues addressed in the proposal are the construction of the C-terminal Z-amino-vinylcysteine motif and a reductive desulfurization approach to form thioether bridges. The approach is independent of microorganisms and their enzymes and offers the potential for a highly convergent approach to the microbisporicins and analogs. The strategy has broad application in lantibiotic synthesis.