Stereoisomeric polycyclic natural products are important for drug discovery-based screening campaigns, due to the close correlation of stereochemistry with diversified bioactivities. Nature generates the stereoisomeric yohimbine alkaloids using bioavailable monoterpene secolaganin as the ten-carbon building block. In this work, we reset the stage by the development of a bioinspired coupling, in which the rapid construction of the entire pentacyclic skeleton and the complete control of all five stereogenic centers are achieved through enantioselective kinetic resolution of an achiral, easily accessible synthetic surrogate. The stereochemical diversification from a common intermediate allows for the divergent and collective synthesis of all four stereoisomeric subfamilies of yohimbine alkaloids through orchestrated tackling of thermodynamic and kinetic preference.

立体异构体多环天然产物对于基于药物发现的筛选活动非常重要，因为立体化学与多样化的生物活性密切相关。大自然使用生物可利用的单萜 secolaganin 作为 10 碳结构块生成立体异构体育亨宾生物碱。在这项工作中，我们通过开发生物启发耦合来重置阶段，其中整个五环骨架的快速构建和所有五个立体中心的完全控制是通过非手性的、易于接近的合成替代物的对映选择性动力学分辨率实现的。来自公共中间体的立体化学多样化允许通过精心策划的热力学和动力学偏好处理，实现育亨宾生物碱的所有四个立体异构体亚家族的发散和集体合成。