Asymmetric Total Synthesis of Taxol.

Ya-Jian Hu, Chen-Chen Gu, Xin-Feng Wang, Long Min, Chuang-Chuang Li

Journal of the American Chemical Society 2021 Oct 27

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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.

Citation

Ya-Jian Hu, Chen-Chen Gu, Xin-Feng Wang, Long Min, Chuang-Chuang Li. Asymmetric Total Synthesis of Taxol. Journal of the American Chemical Society. 2021 Oct 27;143(42):17862-17870