Methodology towards the synthesis of complex stereochemically dense natural products

项目摘要/摘要 哌啶杂环是一种特殊的基序，存在于无数生物活性分子中，包括 天然产品和药物。作为化学治疗中最普遍的含氮杂环， 哌啶类药物在众多的重磅炸弹药物中都有应用。由于哌啶类药物的流行，新的和 获取这一主题的创新方法仍然非常受欢迎。紧张的炔中间体，如 苯乙炔和哌啶酮已被证明是实现这一目的的有用中间体，然而环加成 这些支架通常会导致SP2中心的引入。高活性环烯烃的使用引入了 通过建立SP3中心和邻近的立体中心增加了一层复杂性。建议的研究目标 发展了第一个3，4-氮杂环己基烯Diels-Alder反应，能够获得修饰的哌啶类化合物， 拥有第四纪中心。然后，这一新策略将被用来完成简明的总合成 曼扎明生物碱刺五加内酯。

Project Summary/Abstract The piperidine heterocycle is a privileged motif that appears in countless bioactive molecules, including natural products and drugs. As the most prevalent nitrogen-containing heterocycle in chemical therapeutics, the piperidine motif is featured in a plethora of blockbuster drugs. Due to the prevalence of piperidines, new and innovative methodologies to access this motif remain highly sought after. Strained alkyne intermediates such as benzyne and piperidyne have proven to be useful intermediates towards this end, however cycloadditions to these scaffolds typically lead to the introduction of sp2 centers. The use of highly reactive cyclic allenes introduces an added layer of complexity by building an sp3 center and vicinal stereocenters. The proposed research aims to develop the first 3,4-azacyclohexylallne Diels-Alder reaction capable of accessing decorated piperidines that possess quaternary centers. This new strategy will then be employed to complete a concise total synthesis of the manzamine alkaloid Acantholactone.