Total synthesis of taxol
K. C. Nicolaou*†, Z. Yang*, J. J. Liu*, H. Ueno*, P. G. Nantermet*, R. K. Guy*, C. F. Claiborne*, J. Renaud*, E. A. Couladouros*, K. Paulvannan* & E. J. Sorensen*†
*Department of Chemistry, The Scripps Research Institute, 10666 North Torrey Pines Road, La Jolla, California 92037, USA
†Department of Chemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
TAXOL1–4, a substance originally isolated from the Pacific yew tree (Taxus brevifolia) more than two decades ago, has recently been approved for the clinical treatment of cancer patients. Hailed as having provided one of the most significant advances in cancer therapy5, this molecule exerts its anticancer activity by inhibiting mitosis through enhancement of the polymerization of tubulin and consequent stabilization of microtubules6. The scarcity of taxol and the ecological impact of harvesting it have prompted extensive searches for alternative sources including semisynthesis, cellular culture production and chemical synthesis2,3. The latter has been attempted for almost two decades, but these attempts have been thwarted by the magnitude of the synthetic challenge. Here we report the total synthesis of taxol by a convergent strategy, which opens a chemical pathway for the production of both the natural product itself and a variety of designed taxoids.
||Wani, M. C., Taylor, H. L., Wall, M. E., Coggon, P. & McPhail, A. T. J. Am. chem. Soc. 93, 2325−2327 (1971). | Article | PubMed | ISI | ChemPort |
||Nicolaou, K. C., Dai, W.-M. & Guy, R. K Angew. Chem. int. Edn engl. 33, 15−44 (1994).
||Guenard, D., Gueritte-Voegelein, F. & Poitier, P. Acct Chem. Res. 26, 160−167 (1993). | ChemPort |
||Rowinksy, E. K., Cazenave, L. A. & Donehower, R. C. J. natn. Cancer Inst. 82, 1247−1259 (1990).
||Paclitaxel (Taxol) Investigations Workshop Semin. Oncol. 20 (4, Suppl. 3), 1−60 (1993).
||Schiff, P. B., Fant, J. & Horwitz, S. B. Nature 277, 665−667 (1979). | PubMed | ChemPort |
||Nicolaou, K. C., Hwang, C.-K., Sorensen, E. J. & Claiborne, C. F. J. chem. Soc., chem. Commun. 1117−1118 (1992). | Article | ChemPort |
||Chamberlin, A. R. & Bloom, S. H. Org. React. 39, 1−83 (1990). | ChemPort |
||McMurry, J. E. Chem. Rev. 89, 1513−1524 (1989). | Article | ChemPort |
||Nicolaou, K. C., Nantermet, P. G., Ueno, H. & Guy, R. K. J. chem. Soc., chem. Commun. 295−296 (1994). | Article | ChemPort |
||Ojima, I. et al. Tetrahedron 48, 6985−7012 (1992). | Article | ChemPort |
||Nicolaou, K. C., Liu, J. J., Hwang, C.-K., Dai, W.-M. & Guy, R. K. J. chem. Soc., chem. Commun. 1118−1120 (1992). | Article | ChemPort |
||Nicolaou, K. C., Yang, Z., Sorensen, E. J. & Nakada, M. J. chem. Soc., chem. Commun. 1024−1026 (1993). | Article | ChemPort |
||Griffith, W. P., Ley, S. V. Aldrichimica Acta. 23, 13−19 (1990). | ChemPort |
||Sharpless, K. B. & Verhoeven, T. R. Aldrichimica Acta, 12, 63−74 (1979). | ChemPort |
||Magee, T. V., Bornmann, W. G., Isaacs, R. C. A. & Danishefsky, S. J. J. org. Chem. 57, 3274−3276 (1992). | Article | ChemPort |
© 1994 Nature Publishing Group