1. Total synthesis of sarcodictyins A and B and studies toward the synthesis of garsubellin A. 2. Design and solid phase synthesis of natural product like combinatorial libraries

Biologically active natural products serve important roles in both chemistry and medicine. In this thesis, studies aimed at the solution and solid phase syntheses of several natural products and their analogs are described. First, the sarcodictyins are a collection of marine-derived diterpenoids that exhibit potent cytotoxicities against several cancer cell lines. Interestingly, these compounds function by inducing tubulin polymerization and stabilizing microtubules in a mechanism similar to that of Taxol™. The total syntheses of sarcodictyins A and B are presented along with a summary of the structure-activity relationships derived for this new class of anticancer agents. Second, studies towards the synthesis of garsubellin A which resulted in the construction of the fully functionalized core of this molecule are described. Interest in garsubellin A as a synthetic target resulted from its neurotrophic-like properties in several in vitro assays. Finally, preliminary efforts to achieve a solid phase synthesis of garsubellin A resulted in the development of a novel selenium based solid phase method for the synthesis of small molecule libraries. This strategy was subsequently applied to the solid phase synthesis of several benzopyran containing natural products as well as to the synthesis of a 10,000-membered discovery-oriented combinatorial library for use in chemical biology studies.