Abstract:
Natural products and their analogues are significant sources of therapeutic lead compounds. However, synthetic strategies for generating large collections of these molecules remain a significant challenge. The most difficult step in their synthesis is the design of a common intermediate that can be easily transformed into natural products belonging to different families. This study demonstrates the evolution of synthetic tactics designed to assemble the functionalized piperidines present in indole alkaloids from a common intermediate. More importantly, we also report a previously unknown Ir- and Er-catalyzed dehydrogenative spirocyclization reaction that enables direct access to spirocyclic oxindole alkaloids. As a practical application, the asymmetric total syntheses of 29 natural alkaloids belonging to different families were accomplished by following a uniform synthetic route. The proposed methodology extends the capability of the iridium-catalyzed dehydrogenative coupling reaction to the realm of indole-alkaloid synthesis and provides new opportunities for the efficient preparation of natural product-like molecules.
摘要:
天然产物及其类似物是治疗性先导化合物的重要来源。然而,产生这些分子的大量集合的合成策略仍然是一个重大挑战。它们合成中最困难的步骤是设计一种常见的中间体,该中间体可以很容易地转化为属于不同家族的天然产物。这项研究证明了旨在从常见中间体组装吲哚生物碱中存在的官能化哌啶的合成策略的演变。更重要的是,我们还报道了以前未知的Ir和Er催化的脱氢螺环化反应,该反应可以直接获得螺环羟吲哚生物碱。作为一个实际应用,按照统一的合成路线完成了属于不同家族的29种天然生物碱的不对称总合成。所提出的方法将铱催化的脱氢偶联反应的能力扩展到吲哚-生物碱合成领域,并为有效制备天然产物样分子提供了新的机会。