| This dissertation describes the design, total synthesis and biological evaluation of the epothilone family of natural products and their analogs. A short and highly convergent metathesis macrocyclization strategy was developed to synthesize epothilones A and C. A Stille coupling strategy was developed to attach the aromatic side chain, which led to the total synthesis of epothilone E. Numerous epothilone analogs were quickly and efficiently synthesized using these strategies, and were evaluated for their potential use as anti-cancer agents. These studies led to the establishment of a detailed Structure-Activity Relationship (SAR) for epothilones. Several extremely potent analogs were identified. |
