ORGN 808 |
| The natural epothilones are a family of cytotoxic macrolides isolated in the early 1990s from the myxobacterium, Sorangium cellulosum. The epothilones are microtubule-stabilizing agents with a mode of action similar to paclitaxel. Both epothilone B (2) and D (4) are under evaluation as anticancer agents. Ixabepilone (5), a semisynthetic analog of epothilone B, is currently in Phase III clinical trials. We will describe an efficient and practical process suitable for the preparation of ixabepilone, starting from epothilone B, on commercial scale, and highlight the subtle changes in reagents and concentration that had a dramatic effect on the yield and quality. The three-step, one-pot reaction sequence and subsequent crystallization gave the desired crystalline polymorph of 5 in 70 % overall yield.
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Combinatorial, Parallel and Process Chemistry, Heterocycles, Aromatics, New Reactions and Methodology
8:00 PM-10:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster
Sci-Mix
Division of Organic Chemistry |
