Epoxidation of the olefin in 10-deacetoxybaccatin III (6) and 10-deacetoxypaclitaxel (9) was accomplished with meta-chloroperbenzoic acid leading to a novel pentacyclic ring system. Hydroxyl directed delivery of the epoxidizing agent did not appear to play a role in the stereoselectivity of the reaction as epoxidation occurred at the β-face of the molecule. 10-Deacetoxy-11,12-epoxypaclitaxel (10) proved to be more active than paclitaxel (1) in the microtubule assembly assay and three-fold less cytotoxic than paclitaxel against B16 melanoma cells.
Bibliographical noteFunding Information:
The authors wish to thank the National Cancer Institute for financial paclitaxel for these studies.
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