Total Synthesis of (+)- and (−)-Decursivine and (±)-Serotobenine through a Cascade Witkop Photocyclization/Elimination/Addition Sequence: Scope and Mechanistic Insights

Authors

  • Weimin Hu,

    1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd. 38, Beijing 100191 (P. R. China), Fax: (+86) 10-82805166
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  • Hua Qin,

    1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd. 38, Beijing 100191 (P. R. China), Fax: (+86) 10-82805166
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  • Prof. Yuxin Cui,

    1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd. 38, Beijing 100191 (P. R. China), Fax: (+86) 10-82805166
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  • Prof. Yanxing Jia

    Corresponding author
    1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd. 38, Beijing 100191 (P. R. China), Fax: (+86) 10-82805166
    2. State Key Laboratory of Applied Organic Chemistry, Lanzhou University Lanzhou 730000 (P. R. China)
    • State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd. 38, Beijing 100191 (P. R. China), Fax: (+86) 10-82805166
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Abstract

In this article, the total syntheses of antimalarial compound decursivine and its biologically inactive sibling serotobenine are presented. The biomimetic synthesis of (±)-serotobenine was investigated first, but failed. During the subsequent investigation of other synthetic routes, we discovered a new cascade Witkop photocyclization/elimination/addition sequence, which enabled the expedient synthesis of not only racemic decursivine and serotobenine, but also enantiopure (+)- and (−)-decursivine and a variety of their analogues. The present syntheses represent the shortest pathway for the total synthesis of decursivine and serotobenine to date. Moreover, the newly developed cascade sequence for the total synthesis of decursivine does not need any protecting steps. The scope and the reaction mechanism of the cascade sequence were also studied. A rational mechanism for the cascade sequence is proposed, which is consistent with the previous studies and our current experimental results.

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