| Abstract
| - A convergent ring-closing metathesis strategy has been employed for the highly concise synthesesof 10,11-dehydro-13,14-[17]desoxyepothilone B ([17]ddEpoB) and 10,11-dehydro-14,15-[18]desoxyepothilone B ([18]ddEpoB), which are 17- and 18-membered ring homologues of 10,11-dehydro-12,13-desoxyepothilone B ([16]ddEpoB or epothilone 490). We have demonstrated that the ring-closing metathesis (RCM) provides [17]ddEpoB or [18]ddEpoB with a high level of stereocontrol inthe generation of the desired olefin in the products. These analogues were evaluated for antitumoractivity. The results from the in vitro assays revealed that the [17]ddEpoB analogue is highly activeagainst various tumor cell lines with a potency comparable to that of [16]ddEpoB. This is the firstexample of a 17-membered ring macrolactone epothilone that has retained its antitumor activity.In contrast, the biological data revealed that [18]ddEpoB is significantly less active than either[17]ddEpoB or the parent [16]ddEpoB.
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