Grant: Discovery Grants Program - Individual

The construction of architecturally challenging structural motifs in a predictable and expeditious manner remains a Grand Challenge for synthetic organic chemistry. This limitation has severely limited the ability to facilitate Structure-Activity Relationship Studies in a range of biologically interesting molecules, which has limited the exploitation of many interesting and potentially useful lead compounds. Natural products have historically proven reliable lead compounds for drug discovery. For example, these agents have inspired over 60% of the anticancer agents and 70% of the antibiotics entering clinical trials in the last 30 years. Nevertheless, many companies have abandoned natural products due to the perceived problems associated with the preparation of libraries of natural product analogues for detailed Structure Activity Relationship Studies. Transition metal-catalyzed reactions facilitate the construction of structural motifs that are generally not accessible via conventional methods making these reactions an extremely powerful tool for target directed synthesis. Nevertheless, many of the developments in this area involve tedious catalyst tuning and optimization of reaction conditions. We believe that a combined theoretical/experimental approach will expedite this process by delineating the origin of selectivity and thereby provide solutions to longstanding problems in a manner that would be infinitely more challenging through empirical studies. Hence, in contrast to enzymes, which evolve through multiple iterations, i.e. evolutionary development, this approach should expedite catalyst identification and development by providing insight into new chemical reactivity. We anticipate that this program will result in the development of state-of-the-art transformations that facilitate the construction of complex molecules in an efficient, selective and atom-economical manner. Hence, this work will expand the current ""tool-kit"" of chemical reactions, which will facilitate the construction of biologically important structures in a more expeditious manner and provide cutting-edge HQP training.