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A semisynthetic route to epothilone cyclopropanes from epothilones A and B
is described. Of significance, the deoxygenation of the 12,13- epoxide to g
ive the corresponding olefin was achieved with high efficiency. The title c
ompounds (8, 9) were active in both tubulin polymerization and cytotoxicity
assays, which is in direct contrast to a previously published report. Thes
e results provide further evidence that the role of the 12,13 epoxide of ep
othilones is largely conformational and argue against some of the current p
harmacophore models.