Enantioselective Syntheses of Wickerols A and B.

The evolution of a successful strategy for the synthesis of the strained, cage-like antiviral diterpenoids wickerols A and B is described. Initial attempts to access the carbocyclic core were surprisingly challenging and in retrospect, presaged the many detours needed to ultimately arrive at the fully adorned wickerol architecture. In most cases, conditions to trigger desired outcomes with respect to both reactivity and stereochemistry were hard-won. The successful synthesis ultimately leveraged alkenes in virtually all productive bond-forming events. A series of conjugate addition reactions generated the fused tricyclic core, a Claisen rearrangement was used to install an otherwise unmanageable methyl-bearing stereogenic center, and a Prins cyclization closed the strained bridging ring. This final reaction proved enormously interesting because the strain of the ring system permitted diversion of the presumed initial Prins product into several different scaffolds.

本文描述了一种成功合成具有张力的笼状抗病毒二萜类化合物wickerols A和B的策略的演变过程。最初获取碳环核心的尝试极具挑战性，事后看来，这预示着最终实现完全修饰的wickerol结构需要经历许多迂回曲折。在大多数情况下，要获得关于反应活性和立体化学的理想结果，其条件来之不易。成功的合成最终在几乎所有有效的成键过程中都利用了烯烃。一系列共轭加成反应生成了稠合的三环核心，利用克莱森重排来构建一个原本难以控制的含甲基的手性中心，普林斯环化反应构建了具有张力的桥环。最后这个反应非常有趣，因为环系的张力使得假定的初始普林斯产物能够转化为几种不同的结构。