CAREER: Synthesis of Bridged Polycyclic Natural Products via Intramolecular C-H Insertion

University Of Houston, Houston TX

Investigators

Abstract

Through this award, supported by the Chemical Synthesis Program of the Division of Chemistry, Prof. Jeremy A. May of the University of Houston is developing a general method for the chemical synthesis of a variety of biologically active bridged polycyclic natural products. While such structures in the past have required disparate strategic approaches, the use of a cascade reaction sequence efficiently provides a variety of these molecules with control over the molecular bonding. Highly reactive carbene intermediates, carbon-carbon triple bonds that are covalently linked, and dimeric rhodium catalysts allow multiple chemical bonds, including highly strained cyclic structures, to be synthesized in one reaction. As the reaction sequence forms its final chemical bond through a C-H bond insertion, no prior modification of the substrate at the site of this insertion is required, which greatly increases efficiency, maximizes flexibility, and minimizes waste. The controlling elements for the reactivity are under study, and new catalysts for the transformation are being designed. The structural motifs produced by this synthesis technology are found in numerous biologically active compounds produced naturally in minute quantities. Since these natural products display antimalarial, anticancer, antimicrobial, and other useful properties, the synthetic strategy is being applied to these targets to obtain sufficient material for further study. Moreover, the rapid nature of the chemical synthesis allows modifications to the parent structure to be made so that the key molecular elements for biological activity may be identified. Thus, this effort has a broader impact on disease mechanisms, natural product biology, and several fields of chemistry. The research effort under this award is integrated in multiple levels of education, as the graduate, undergraduate, and junior high students who participate learn principles of biochemistry, organic chemistry, medicinal chemistry, catalysis, and scientific analysis.