ORGN 678 |
| Epothilones (1) are natural product microtubule-stabilizing agents with potent antitumor activity in vitro and in vivo. Seven epothilone-derived agents have entered clinical trials in humans, all of which are closely related structurally to the natural product leads Epo A and B. Our own work aims at the discovery of analogs with significantly altered structural features, thus creating new scaffolds for microtubule inhibition as new lead structures for anticancer drug discovery. In this context, we have prepared analogs of the general structures 2 and 3, with macrocycle formation being affected either through Yamaguchi-type macrolactonization or through ring-closing olefin metathesis (RCM) between C9 and C10 with 2nd generation Grubbs catalyst. In spite of significant architectural differences between these analogs and natural epothilones, the biological activity of individual compounds from both structural series is within the same potency range as that of Epo A or B.
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Biologically-Related Molecules and Processes
8:00 AM-12:00 PM, Wednesday, August 22, 2007 BCEC -- 258B, Oral
Division of Organic Chemistry |
