Synthesis and Study of Medicinally Important Molecules

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Project Summary/Abstract The goal of our research program is to innovate the strategy and methodology of organic synthesis and use these innovations to solve problems of biological and medicinal importance and ultimately impact human health. Our program focuses on the synthesis and study of both natural and unnatural molecules with potential for the treatment of cancer, neurological disorders, and drug resistant infectious diseases. We view the completion of a chemical synthesis as the beginning of a larger and deeper scholarly inquiry. It would enable us to profile the biology of the selected natural products and rationally designed small molecules, decipher their mechanism of actions, and optimize the lead compounds into biological probes and novel therapeutics. The selected terpenoid and alkaloid natural products represent both the state-of-the-art challenges for complex molecule synthesis as well as promising lead compounds for novel therapeutic development. Their structural complexity, natural scarcity, and unknown mechanism of actions have significantly hampered their biomedical development. We aim to fill this gap and move these molecules forward in the drug discovery pipeline with a multi-faceted approach centered on innovative chemical synthesis. The expected outcomes of this research will provide (i) new reactions and strategies in the toolbox of both medicinal chemists and synthetic chemists to prepare functional molecules, (ii) a reliable access to the selected target molecules with therapeutic importance, (iii) a collection of medicinally relevant molecules featuring structural novelty, complexity, and diversity for further and larger biological evaluations in academic institutions and pharmaceutical industries, and (iv) novel anticancer, anti-neurodegenerative and antimicrobial lead compounds with potentially novel mode of actions for in vivo and clinical evaluations.