TOTAL SYNTHESIS OF TAXOL

TAXOL(1-4), a substance originally isolated from the Pacific yew tree (Taxus brevifolia) more than two decades ago, has recently been approv ed for the clinical treatment of cancer patients. Hailed as having pro vided one of the most significant advances in cancer therapy(5), this molecule exerts its anticancer activity by inhibiting mitosis through enhancement of the polymerization of tubulin and consequent stabilizat ion of microtubules(6). The scarcity of taxol and the ecological impac t of harvesting it have prompted extensive searches for alternative so urces including semisynthesis, cellular culture production and chemica l synthesis(2,3). The latter has been attempted for almost two decades , but these attempts have been thwarted by the magnitude of the synthe tic challenge. Here we report the total synthesis of taxol by a conver gent strategy, which opens a chemical pathway for the production of bo th the natural product itself and a variety of designed taxoids.