Grant: Discovery Grants Program - Individual

Synthetic chemists strive to build molecules, simple and complex, real and imaginary, which produce tomorrow's beneficial medicines and materials for humankind. They apply tested theories and new hypotheses to develop new types of starting materials and reagents, click them together in different ways like Lego blocks, and create a multitude of new products: a combination drug for AIDS, a derivative of taxol for breast cancer, a crucially needed anti-Alzheimer's drug, a smart material or a sensor. Our major themes concern the discovery and development of new synthetic methods for aromatics and heteroaromatics based on anionic and transition metal catalyzed reactions. We use directed ortho metalation (DoM) chemistry as a conceptual platform for invention of efficient synthetic methods, construction of bioactive and natural products and new chiral ligands, and for uncovering new links to emerging reactions in organic synthesis. MAJOR GOALS. We will pursue a number of recent discoveries in our labs to contribute to contemporary synthetic chemistry: a) reactions we have devised and developed (DoM-Suzuki) which are finding increased utility in academic and industrial laboratories, b) new reactions (e.g. catalytic C-O, C-N bond coupling processes, DoM-Petasis processes for bioactive benzylamines, unprecedented DoM-halogen rearrangements for biological pyridines, e.g. Vitamin B6) which we shall establish as robust methods for the same purpose, and c) application of discovered reactions to the total synthesis of biologically significant natural products. SYNTHETIC AROMATIC CHEMISTRY is a major component of the chemical enterprise today. Over 80% of current therapeutic agents contain aromatic or heteroaromatic moieties. Our reactions are being used by industry (e.g. Monsanto, Pfizer, BMS, Merck) for the multi-kg production of drugs, agrochemicals, and liquid crystals. IN OUR EFFORTS we aim to advance fundamental research, to heed the needs of medicinal and process chemists, and to train students for independent careers (68 MSc, PhD and postdoc students have been trained in the past 6 years).