subject of considerable synthetic effort. Three total syntheses of the compound have recently appeared.230-232 These and later total syntheses will create additional material with which to study this interesting molecule and its analogs.

Several other molecules of natural origin have been reported to be stabilizers of microtubules (Figure 47). The isolation and characterization of WS9885B 104 have been reported.233 This material was found to possess cytotoxicity similar to paclitaxel.234 A family of polyisoprenyl benzophenones (e.g., 105) has been isolated from the fruit of the Malaysian plant Garciniapyrifera and has shown low micromolar cytotoxicities.235 Although 105 is only weakly cytotoxic and structurally complex, it is isolated in relatively large quantities (27 g of 105 from 1.8 kg of dried fruit) and has served as the starting point for an analog program based on semisynthesis. The polycyclic alkaloid (-)-rhainilum 106 was isolated from Melodinus australia and other species.236 Although this compound and its congeners are only weak (micromolar) cytotoxins, the possibility remains that more potent analogs may be identified. Synthetic Microtubule-Stabilizing Agents

Several synthetic microtubule stabilizers have also been identified (Figure 48). Although the best of these compounds are significantly less potent than paclitaxel and other clinically useful microtubule-stabilizing agents, they are as a group

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