Syntheses of natural products OSW-1, superstolide A and their derivatives [thesis]

Yan Mei
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 different from other well-known anticancer agents. However, its mechanism still remains 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 toxicological experiments have also been
more » ... ve 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, simplified analogs and amino analogue were synthesized for the SAR study. 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. This dissertation includes a model study for the construction of the 16-membered macrolactone present in Superstolide A. More specially, there is a focus on the investigation of three crucial carbon-carbon bond-forming reactions in our synthetic strategy including Julia olefination, Suzuki coupling and Horner-Emmons olefination. Abstract Approved: ____________________________________ Thesis Supervisor ____________________________________
doi:10.17077/etd.tau7hfml fatcat:6oe4n4uapfbxvdkoeqrw2hh4vu