Synthesis and biological evaluation of novel taxane terpenoids

CHED 506

Stephanie Gasiorowski1, Jessica L. Tischler1, and Ali R. Zand2. (1) Department of Chemistry, University of Michigan-Flint, 303 E. Kearsly St., Flint, MI 48502, (2) Department of Science and Mathematics, Kettering University, 1700 W. Third Avenue, Flint, MI 48504
Paclitaxel, a diterpene natural product from the Pacific Yew tree, Taxus brevifolia, has emerged as a promising chemotherapeutic agent for treating solid tumors. The taxane family is one of the most challenging synthetic targets due to their unique carbon skeleton. We have used a powerful methodology based on [2+2] photocycloaddition of double bonds to excited phenylketones to synthesize the 8-membered taxane B rings. The methodology allows the synthesis of taxanes with variety of substituents. We have tested the biological activity of these taxanes for microtubule polymerization/ depolymerization. The results of the synthetic efforts and biological assays will be presented.