State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Xue Yuan Rd. 38, Beijing 100191, P. R. China.
Chemistry. 2013 Feb 25;19(9):3139-47. doi: 10.1002/chem.201204137. Epub 2013 Jan 10.
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.
本文报道了抗疟化合物断血流碱及其生物惰性同系物赛洛托品的全合成。首先对（±）-赛洛托品进行了仿生合成研究，但未成功。在随后对其他合成路线的研究中，我们发现了一种新的级联 Witkop 光环化/消除/加成序列，该序列不仅能够方便地合成外消旋的断血流碱和赛洛托品，还能够合成对映纯的（+）-和（-）-断血流碱以及它们的多种类似物。目前的合成方法代表了迄今为止断血流碱和赛洛托品全合成的最短途径。此外，新开发的用于断血流碱全合成的级联序列不需要任何保护步骤。还研究了级联序列的范围和反应机制。提出了一个合理的级联序列机制，该机制与以前的研究和我们目前的实验结果一致。
