Dimeric indolosesquiterpene alkaloids, typically N–N- and C–N-linked xiamycin dimers, feature a pentacyclic framework with four contiguous stereogenic centers at the periphery of a trans-decalin scaffold to which a carbazole unit is attached. In comparison with actual biosynthetic dixiamycin derivatives, we designed C–C-linked xiamycin dimers, aiming to use them as a powerful tool to create unique scaffolds as drug candidates. In this work, we disclose the first synthetic route to access a C–C dimeric indolosesquiterpene skeleton, featuring a hypervalent iodine (PIFA)-catalyzed oxidative dimerization reaction in a single-step operation with overwhelming control over the chemoselectivity and regioselectivity. This strategy has been successfully applied to the synthesis of a C–C dimer of xiamycin A (3) and xiamycin A methyl ester (15) that demonstrates a new synthetic pathway for dimeric indolosesquiterpene alkaloids.

中文翻译：

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吲哚倍半萜生物碱的高度化学选择性氧化二聚：二氧霉素的仿生方法


二聚吲哚半萜生物碱，通常是 N-N- 和 C-N- 连接的夏霉素二聚体，具有五环框架，在反式十氢化萘支架的外围有四个连续的立体中心，咔唑单元连接到该支架上。与实际生物合成的二克霉素衍生物相比，我们设计了C-C连接的二克霉素二聚体，旨在将它们用作创建独特的候选药物支架的强大工具。在这项工作中，我们公开了第一个获得C-C二聚吲哚半萜骨架的合成路线，其特征是高价碘（PIFA）催化的氧化二聚反应在一步操作中具有对化学选择性和区域选择性的压倒性控制。该策略已成功应用于夏霉素 A (3) 和夏霉素 A 甲酯 (15) 的 C-C 二聚体的合成，展示了二聚吲哚半萜生物碱的新合成途径。