Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Chemveda Life Sciences, Pvt. Ltd., Plot No. B - 11/1, IDA Uppal, Hyderabad, Telangana 500039, India.
J Am Chem Soc. 2020 Jun 10;142(23):10526-10533. doi: 10.1021/jacs.0c03592. Epub 2020 May 29.
Taxol (a brand name for paclitaxel) is widely regarded as among the most famed natural isolates ever discovered, and has been the subject of innumerable studies in both basic and applied science. Its documented success as an anticancer agent, coupled with early concerns over supply, stimulated a furious worldwide effort from chemists to provide a solution for its preparation through total synthesis. Those pioneering studies proved the feasibility of retrosynthetically guided access to synthetic Taxol, albeit in minute quantities and with enormous effort. In practice, all medicinal chemistry efforts and eventual commercialization have relied upon natural (plant material) or biosynthetically derived (synthetic biology) supplies. Here we show how a complementary divergent synthetic approach that is holistically patterned off of biosynthetic machinery for terpene synthesis can be used to arrive at Taxol.
紫杉醇（商品名紫杉醇）被广泛认为是有史以来最著名的天然分离物之一，并且已经成为基础科学和应用科学无数研究的主题。它作为抗癌药物的成功，加上早期对供应的担忧，激发了化学家们通过全合成提供其制备方法的全球激烈努力。这些开创性的研究证明了通过反合成指导合成紫杉醇的可行性，尽管数量很少，但需要付出巨大的努力。实际上，所有药物化学的努力和最终的商业化都依赖于天然（植物材料）或生物合成（合成生物学）供应。在这里，我们展示了如何使用整体模仿萜类化合物生物合成机制的互补发散合成方法来合成紫杉醇。
