Shenzhen Grubbs Institute and Department of Chemistry, Southern University of Science and Technology (SUSTech), Shenzhen 518055, China.
Shenzhen Bay Laboratory, Shenzhen 518132, China.
Chem Rev. 2023 Apr 26;123(8):4934-4971. doi: 10.1021/acs.chemrev.2c00763. Epub 2023 Mar 14.
Taxol (paclitaxel), the most well-known taxane diterpenoid, is the best-selling natural-source anticancer drug ever produced and one of the most common prescriptions in the treatment of breast, lung, and ovarian cancers, saving countless lives around the world. Structurally, Taxol possesses a highly oxygenated [6-8-6-4] core bearing 11 stereocenters, seven of which are contiguous chiral centers. Moreover, the extremely strained bicyclo[5.3.1] undecane ring system with a bridgehead double bond is a unique structural feature. All these features make Taxol a highly challenging synthetic target. Tremendous synthetic efforts from more than 60 research groups around the world have already culminated in ten total syntheses and three formal syntheses, as well as more than 60 synthetic model studies of Taxol. This review is intended to provide a long-overdue appraisal of the great achievements in the total syntheses of Taxol reported in the last few decades. In doing so, we summarize the development of synthesis toward Taxol from 1994 to 2022, including the evolution of synthetic strategy for accessing this complex molecular scaffold and key lessons learned from such endeavors. Finally, we briefly discuss the future of the research in this area.
紫杉醇（紫杉醇）是最著名的紫杉烷二萜类化合物，是有史以来销量最好的天然来源抗癌药物，也是治疗乳腺癌、肺癌和卵巢癌最常用的处方之一，为数以百万计的生命带来了希望。从结构上看，紫杉醇具有高度氧化的[6-8-6-4]核心，带有 11 个手性中心，其中 7 个是连续的手性中心。此外，具有桥接双键的极度应变双环[5.3.1]十一烷环系统是其独特的结构特征。所有这些特征使得紫杉醇成为一个极具挑战性的合成目标。全世界 60 多个研究小组进行了大量的合成努力，已经完成了 10 次全合成和 3 次正式合成，以及 60 多次紫杉醇合成模型研究。这篇综述旨在对过去几十年中报道的紫杉醇全合成的巨大成就进行及时的评价。为此，我们总结了从 1994 年到 2022 年紫杉醇的合成进展，包括对这种复杂分子支架进行合成的策略的演变以及从这些努力中吸取的关键经验教训。最后，我们简要讨论了该领域未来的研究方向。
