Total Synthesis of (— )-Epothilone B: An Extension of the Suzuki Coupling Method and Insights into Structure-Activity Relationships of the Epothilones

摘要

Recently, synthetic studies directed to epothilone A (3) culminated in its first .total synthesis. Our synthesis passed through the Z-desoxy compound (4), which underwent highly stereoselective epoxidation with 2,2-dimethyldioxirane, under carefully defined conditions, to yield the desired beta-epoxide. The same myxobacterium of the genus Sorangium that produces 3 also produces epothilone B (1). The latter is significantly more potent than 3 both in antifungal screens and in cytotoxicity assays in some cell lines. Clearly then, there was a strong rationale for preparing epothilone B (1).