Date of Degree
PhD (Doctor of Philosophy)
OSW-1 is a natural saponin and its anticancer activities are 10- to 100-fold more potent than many well-known anticancer agents in clinical use. Its cytotoxicity profile suggests that it may have a unique mode of action that is different from other well-known anticancer agents. However, its mechanism still remains as a mystery after years of study, and no paper has ever been published in this area. Extensive in vitro and in vivo testing has been conducted and toxicology experiments have also been carried out by our collaborator Prof. Huang's laboratory at MD Anderson Cancer Center. In order to identify the pharmacophore and mechanism of OSW-1 and increase its in vivo activity and selectivity, amino analogues are synthesized for the SAR study employing the chemistry developed in our lab.
Superstolide A (1) is a highly potent anti-tumor reagent that was isolated from deep water marine sponge in 1996. The potent anticancer activity, molecular complexity (11 chiral centers) and scarcity in natural resources make this molecule an attractive synthetic target. Currently I am working on the model study for the construction of the 16-membered macrolactone present in Superstolide A. Specifically I am focusing on the investigation of three crucial carbon-carbon bond-forming reactions in our synthetic strategy including Julia olefination, Suzuki coupling and Horner-Emmons olefination.
OSW-1, Superstolide A
Copyright 2009 Yan Mei