With the support of the Organic Dynamics Program in the Chemistry Division, Professor Dean J. Tantillo of the University of California- Davis will perform research that consists of both theoretical and experimental studies of polycyclization mechanisms that are initiated by the generation of an organic reactive intermediate, referred to as Reactive Intermediate Promoted Polycyclization (RIPP) reactions. Polycyclization reactions, single transformations in which molecules with multiple new rings are formed, are among the most efficient chemical transformations known. In many cases, however, the relative importance of geometric, stereoelectronic, electrostatic and hydrophobic effects in controlling the rate, regioselectivity and stereoselectivity of polycyclization is not known. The proposed Modern Quantum Chemistry will be used to elucidate the mechanisms of both synthetic and biosynthetic RIPP reactions in various chemical environments. Particular emphasis will be placed on obtaining a quantitative understanding of catalysis of polycyclization processes using the "theozyme" (theoretical enzyme) method and on the theoretical design of new reactions not previously observed in nature and not previously attempted in the lab, a strategy that Professor Tantillo calls "ab initio reaction design". The overall goal of the proposed research is to provide a detailed set of guidelines for designing efficient polycyclization processes.
The Organic and Macromolecular Chemistry Program supports Professor Dean J. Tantillo of the University of California- Davis whose projects described in this proposal are designed so that students can construct complete stories that involve the development of theoretical models to explain experimental observations, application of these models to the design of new reactions, and testing of these designs through laboratory experiments. The results of these studies will be presented at an annual conference that will be organized during the grant period by the PI and his students, which will bring together theoretical and computational chemists from graduate and undergraduate educational institutions and from the pharmaceutical and software development industries.
