The project addresses the use of phosphate triesters as temporary tethers to generate mono- and bicyclic phosphates, followed by selective cleavage reactions that exploit the latent leaving group ability provided by the phosphate tether. These studies exploit several features inherent to phosphorus, including multi-valency that bestows both chirality and facile coupling pathways, the potential to provide multivalent activation, and an orthogonal stability/reactivity profile that imparts protecting group features in the P-tether. Thus, overall, the phosphate tether serves a multi-faceted role as temporary tether, protecting group, and latent leaving group. This phosphate triester methodology will be applied to the preparation of differentially protected polyols en route to the total synthesis of biologically relevant targets, including the dolabelides, leustroducsin, and fostriecin.
With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Paul R. Hanson of the Department of Chemistry at the University of Kansas. Professor Hanson and his students are developing novel methods for organic synthesis that exploit the unique structural and chemical features of the phosphorus atom. The phosphorus atom plays a multifunctional role in directing and controlling ensuing chemical reactions, affording novel strategies for the synthesis of complex organic molecules displaying interesting biological activity. Professor Hanson also serves as the Director of a Minority Student-Mentoring Program, designed to provide mentors for minority undergraduate and graduate students interested in pursuing careers in the chemical and medical sciences.
