We describe here the diastereocontrolled formal racemic syntheses of tricyclic marine alkaloids, lepadiformines A, B, and C as well as their C2 epimers, featuring divergent and stereoselective syntheses of the N-acetyl-8a-cyanodecahydroquinoline frameworks and the base-mediated intramolecular cyclization to establish the spiral quaternary center of the tricyclic framework from sterically well-defined α-aminonitrile 2. The approach allows us to accomplish the tricyclic core structure efficiently from readily available starting materials through simple operations. An unexpected pair of consecutive epimerizations at two contiguous stereocenters is observed on the basis of single-crystal X-ray analyses of the intermediates and derivatives. The findings have been successfully applied to the total synthesis of 2-epi-lepadiformine C. The epimerization mechanism has been elucidated through a series of deuterium-labelling-controlled experiments.

中文翻译：

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（±）-Lepadiformines A，B和C的非对映体形式合成，以及通过意外的两次连续差向异构化生成的2-epi-Lepadiformine C的不同合成物。

我们在这里描述了三环海洋生物碱，lepadiformines A，B和C及其C2差向异构体的非对映体形式外消旋合成，其特征在于N-乙酰基8a-氰基二十二氢喹啉骨架的发散和立体选择性合成以及碱基介导的分子内环化从空间上明确定义的α-氨基腈2建立三环骨架的螺旋四级中心。该方法使我们能够从容易获得的起始原料通过简单的操作有效地完成三环核的结构。在中间体和衍生物的单晶X射线分析的基础上，观察到了两个相邻立体中心的一对意外的差向异构化。这些发现已成功地应用于2- Epi- lepadiformine C的全合成。通过一系列氘标记控制的实验阐明了差向异构化机制。