THE OLEFIN METATHESIS APPROACH TO EPOTHILONE-A AND ITS ANALOGS

The olefin metathesis approach to epothilone A (1) and several analogu es (39-41, 42-44, 51-57, 58-60, 64-65, and 67-69) is described. Key bu ilding blocks 6-8 were constructed in optically active form and were c oupled and elaborated to olefin metathesis precursor 4 via an aldol re action and an esterification coupling. Olefin metathesis of compound 4 , under the catalytic influence of RuCl2(=CHPh)(PCy3)(2), furnished ci s- and trans-cyclic olefins 3 and 48. Epoxidation of 49 gave epothilon e A (1) and several analogues, whereas epoxidation of 50 resulted in a dditional epothilones. Similar elaboration of isomeric as well as simp ler intermediates resulted in yet another series of epothilone analogu es and model systems.