ABSTRACT DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF (+)-DISCODERMOLIDE ANALOGS AND SYNTHETIC STUDY TOWARDS (–)-PTEROCIDIN Nan Zhang Amos B. Smith, III Chapter one describes the design and synthesis of novel (+)-discodermolide analogs, that featured different saturation degrees of the terminal diene system and various lactone moieties. Biological evaluation via multiparameter dose-response analysis identified analog B2 as lead congener with superior efficacy towards different cancer cell lines. The high-resolution crystal structure of the B2-tubulin complex was obtained, shedding light on future design of new (+)-discodermolide analogs based on a better understanding of binding mechanism at molecular level. Chapter two describes a “high-risk” synthetic study towards the natural product (–)-pterocidin. Besides cytotoxicity in different cancer cell lines at the low micromolar level, (–)-pterocidin has potent anti-invasive activity at non-cytotoxic concentration. A “high-risk” synthetic strategy was designed as a showcase of Type II Anion Relay Chemistry comprising a multicomponent union involving an aldehyde fragment, a bifunctional linchpin and a dienyl ether moiety. The key union has been demonstrated and the final step of the synthesis is currently under investigation.