Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States.
J Am Chem Soc. 2023 Apr 5;145(13):7278-7287. doi: 10.1021/jacs.2c13146. Epub 2023 Mar 23.
Strempeliopidine is a member of the monoterpenoid bisindole alkaloid family, a class of natural products that have been shown to elicit an array of biological responses including modulating protein-protein interactions in human cancer cells. Our synthesis of strempeliopidine leverages palladium-catalyzed decarboxylative asymmetric allylic alkylations to install the requisite all-carbon quaternary centers found in each of the two monomeric natural products, aspidospermidine and eburnamine. Initial studies employing Suzuki-Miyaura cross-coupling followed by diastereoselective hydrogenation provided evidence for a structural reassignment of the natural product. Our final synthetic sequence employs a diastereoselective Petasis borono-Mannich reaction to couple eburnamine to a trifluoroborate aspidospermidine derivative. These convergent approaches enabled the synthesis of eight diastereomers of this heterodimer and offer support for the reassignment of the absolute configuration of strempeliopidine.
斯特雷姆佩利奥平啶是单萜双吲哚生物碱家族的一员，这类天然产物已被证明能引起多种生物反应，包括调节人类癌细胞中的蛋白质-蛋白质相互作用。我们的斯特雷姆佩利奥平啶合成利用钯催化的脱羧不对称烯丙基烷基化反应，在每个单体天然产物（即阿朴斯多品碱和依波加因）中引入所需的全碳季碳原子。最初的研究采用 Suzuki-Miyaura 交叉偶联反应，然后进行非对映选择性氢化，为天然产物的结构重分配提供了证据。我们的最终合成序列采用非对映选择性 Petasis 硼烷-Mannich 反应将依波加因与三氟硼酸阿朴斯多品碱衍生物偶联。这些收敛性方法使该杂二聚体的八种非对映异构体的合成成为可能，并为斯特雷姆佩利奥平啶的绝对构型的重新分配提供了支持。
