Professor Morken is studying the sequential Aldol-Tischenko reaction that has been found to undergo catalysis by lithium alkoxides. A variety of chiral lithium alkoxides as well as alkoxides of other metals such as magnesium will be tested for their ability to catalyze the reaction while imparting control over its absolute stereochemistry. In order to simultaneously assess the reactivity of large numbers of catalysts, a thermographic screening technique will be employed. Since the Aldol-Tischenko reaction sequence has the potential to create a single 1,3-diol monoester from three different component aldehydes or ketones, a synthesis of the anticancer agent epithilone will be attempted. The key three-component assembly of the formal target molecule will create two asymmetric centers, a new C-C bond, and the ester functionality of the incipient macrolactone. Professor Morken's teaching focus is on the introduction of a multidisciplinary approach to scientific problem-solving. This will occur primarily in the laboratory portion of introductory chemistry courses, starting with sophomore honors organic students. The experimental focus will be the use of combinatorial synthesis for the preparation of Diels-Alder adducts that will be characterized using simple biochemical screens.
With this CAREER award, the Synthetic Organic Program supports the teaching and research activities of Dr. James P. Morken of the University of North Carolina, Chapel Hill. The research aspect of these activities involves the combination of two or three molecules into a single unit while controlling its ultimate stereochemistry (three-dimensional structure). A specific anticancer compound, epithilone, is targeted as a demonstration of the power of this method to rapidly assemble a complex molecule from simpler component parts. Professor Morken's teaching efforts emphasize a multidisciplinary approach to the undergraduate teaching laboratory where combinatorial chemistry will be used as a vehicle for discovery-based learning. Students will carry out reactions on solid supports and use a number of techniques to characterize their products, which will include some that are known to be active in biochemical assays.
