Synthesis toward Epothilone A: Coupling Reaction between the Sulfone of C1-C10 and the Allylic Bromide of C11-C21

Macrolide epothilones 1 and 2, isolated by Höfle et al. from the myxobacterium Sorangium cellulosum, have been drawing considerable attention because of their novel struc-tural features and paclitaxel (Taxol®)-like antitumor activ-ity.1 The biological activity of epothilones came from their binding and stabilization of the microtubule assembly.2 But epothilones differ from paclitaxel in respect of retaining activity against multidrug-resistant cells, solubility in water, and their easy availability by fermentation. The synthetic studies have been recently exploited by many organic chemists.3 Our retrosynthetic analysis of epothilones suggests disconnection at C10-C11 bond and lactonic bond. Thus, our synthetic plans require two building blocks 3 and 4 with appropriate protecting groups (Scheme 1). The coupling reaction between the allylic bromide 3 an