Asymmetric Total Synthesis of Taxol
Asymmetric Total Synthesis of Taxol
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DOI：
10.1021/jacs.1c09637
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发表时间：
2021-10-12
影响因子：
15
通讯作者：
Li, Chuang-Chuang
中科院分区：
文献类型：
--
作者：
Hu, Ya-Jian;Gu, Chen-Chen;Li, Chuang-Chuang
紫杉醇是最著名的天然二萜类化合物之一，也是一种重要的抗肿瘤药物。紫杉醇代表了一个巨大的合成挑战，并引起了合成界的极大兴趣。然而，在所有以前的紫杉醇合成中，没有报道通过C1-C2键形成闭合所需的八元环。此外，紫杉醇耐药肿瘤的存在和紫杉醇的副作用使得开发新的方法来合成紫杉醇及其衍生物非常必要。在这里，我们报告了紫杉醇的不对称全合成使用一个简洁的方法，通过19个分离的中间体。通过非对映选择性的分子内SmI 2介导的频哪醇偶联反应形成C1-C2键，有效地构建了具有合成挑战性的八元环。独特的仿生氧烯反应和新开发的简单串联C2-苯甲酸酯形成和C13侧链安装提高了合成效率。在光照条件下的温和氧烯反应可能是紫杉醇生物合成中的一个替代反应。这种新的融合方法将允许紫杉醇衍生物的多样化创造，以实现进一步的生物学研究。
Taxol is one of the most famous natural diterpenoids and an important anticancer medicine. Taxol represents a formidable synthetic challenge and has prompted significant interest from the synthetic community. However, in all the previous syntheses of Taxol, there have been no reports of closing the desired eight-membered ring through C1-C2 bond formation. Furthermore, the existence of Taxol-resistant tumors and side effects of Taxol make the development of new approaches to synthesize Taxol and its derivatives highly desirable. Here, we report the asymmetric total synthesis of Taxol using a concise approach through 19 isolated intermediates. The synthetically challenging eight-membered ring was constructed efficiently by a diastereoselective intramolecular SmI2-mediated pinacol coupling reaction to form the C1-C2 bond. The unique biomimetic oxygen ene reaction and the newly developed facile tandem C2-benzoate formation and C13 side chain installation improved the efficiency of the synthesis. The mild oxygen ene reaction under light conditions would be an alternative reaction involved in Taxol biosynthesis. This new convergent approach will allow the diverse creation of Taxol derivatives to enable further biological research.