Synthetic Methods Development and Drug Discovery
Research in the Dong group aims to harness the power of transition-metal catalysts to address synthetic challenges of biological importance. The overall program encompasses the disciplines of new synthetic methods development and drug discovery. In the former area, we are working to activate and subsequently functionalize C—H and C—C bonds in organic molecules. These bonds are considered as most inert chemical bonds in nature; however, selective cleavage and derivatization of these bonds will dramatically enhance the efficiency in preparing complex molecules. We are now developing new types of “bio-inspired” bifunctional catalytic systems based on the unique reactivity of transition metals, and anticipate that these catalysts will provide control of both the reactivity and selectivity. The specific challenges we are trying to address are two-fold: to control the site-selectivity in a C—H functionalization process and to enable C—C activation as a useful/practical means for organic synthesis. It is expected that success of these efforts would significantly enhance the synthetic efficiency and even revolutionize the way that chemists synthesize complex organic molecules.
With powerful synthetic tools in hand, we will next apply these methods to the synthesis of biologically important and synthetically challenging natural products. The objective is to efficiently access these targets in a rapid and economical fashion. Towards this end, we will further construct natural product-based small-molecule libraries through a two-stage diversification using both the C—C and C—H activation methods. Following initial high-throughput screening, we will then collaborate with experts from the field of experimental therapeutics to perform in-depth biological evaluation. Given that the molecules in these libraries are structurally related to the natural products that exhibit the desired biological profiles, it provides a much better opportunity to discover drug leads with improved properties. The long-term goal here is to go beyond conventional “random screen” and enable “radar screen” for acceleration of drug discovery.