Synthesis Of 2'-α-Hydroxyalkanyl Taxanes And Their Bio-activity Study

The diterpenoid natural product paclitaxel, originally extracted from Taxusbrevifolia, and its semi-synthesized derivative docetaxel are now the most importantmembers of the clinically useful anticancer agents.A brief review of paclitaxel and docetaxel's semi-synthesis and theirStructure-Activity Relationship is followed. Our study focused on the modification onC-2' of the C-13 side chain. Via β-lactam approach, we designed and synthesized2',3'-syn, 2',3'-anti-2'-α-hydroxyethyl taxanes and 2'-hydroxy-2'-hydroxymathyltaxanes with different configurations.Although the potency of these compounds toward MCF-7 decreases about1000-fold compared with paclitaxel and docetaxel, the potency of some synthesized2',3'-anti-2'-α-hydroxyethyl taxanes toward MCF-7/ADR is similar to or even betterthan that of paclitaxel and docetaxel. The results indicate that further modification ofC-2' site may lead to the discovery of some novel paclitaxel analog with improvedactivity.