Synthetic Pyridinium Salt Photochemistry

University Of New Mexico, Albuquerque NM

Investigators

Abstract

This research program addresses the development of novel synthetic methods that can be applied to the design of concise routes for the preparation of biomedically important targets. The investigations build on an intriguing pyridinium salt photocyclization reaction, discovered nearly 30 years ago, which will be transformed into a potent methodology for the stereocontrolled synthesis of highly functionalized aminocyclopentenes. The generality of this photocyclization reaction will be probed through an exploration of the photochemistry of fused-pyridinium and polycondensed N-heteroaromatic salts. Absolute stereochemical control of the pyridinium salt photocyclization reactions by N-linked carbohydrate auxiliaries and chiral tethers will be also investigated. Stereocontrolled pyridinium salt photocyclization reactions will be used as key steps in short sequences for the synthesis of the potent trehalase inhibitor (+)-trehazoline, the proteasome inhibitor (+)-lactacystin, and the glycosidase inhibitors (+)-castanospermine, uniflorine-A and related polyhydroxylated indolizidines and quinolizidines. With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Dr. Patrick S. Mariano, of the Department of Chemistry at the University of New Mexico. Professor Mariano and his students are exploring light-driven ("photochemical") reactions as potential tools to effect the controlled synthesis of various classes of organic molecules. The investigation concentrates on synthetic methodology development, but it is more broadly designed to address issues that relate to the synthesis of biomedically important targets and the chemistry of the high energy intermediate molecules formed in photochemical processes. General contributions will be made to the field of synthetic organic chemistry, while equally significant is the impact that the studies will have on chemical education, with this project providing a broad, comprehensive foundation for students.