钯催化的苯并含氮、氧和硫稠杂环的高效合成和在天然产物 Goniomitine, Aspidospermidine和 Galanthamine 合成中的应用

杂环类化合物广泛存在于天然产物和具有生理活性的分子之中，是新药设计和研发中的优势骨架，针对此类化合物的合成一直是有机化学家研究的热点之一。人们报道了很多杂环合成的方法，但是针对稠杂环这种复杂结构的合成还具有很大的挑战性。本课题拟通过研究钯催化的一系列分子内环化反应来合成稠环杂环，包括1)通过环化/酰基迁移反应合成[1,2-a]-稠环吲哚；2)通过设计含亲核试剂的底物实现吲哚啉的不对称合成，3)不对称催化合成[b,d]-苯并二氢呋喃和苯并二氢噻吩。我们的目的是发展从简单原料出发合成这些稠杂环的有效方法，并应用在天然产物 goniomitine、aspidospermidine和galanthamine，以及药物分子 FK-1052的合成中去，为这些复杂分子和其类似物的合成提供借鉴。

Heterocycles are ubiquitous structures in natural products and bio-important molecules, and have been recognized as the privileged scaffolds for library design and drug discovery. Numerous efforts have been dedicated to heterocyle syntheses, however, there are only a handful of approaches that can lead to polycyclicheterocycles, yet none of them is efficient or practical enough. We proposed here a strategy to access such structures by palladium-catalyzed intramolecular reactions, including 1) synthesis of polycyclic-[1,2-a]-indoles by intramolecular cyclization/acyl migration reactions; 2) construction of 3-quaternary carbon-containing indolines by cyclization/in situ nucleophilic trap processs; and 3) formation of polycyclicdihydrobenzo-[b,d]-furans and –thiopenes using asymmetric catalysis. It is our goal to establish a simple and efficient method for the access of polycyclicheterocycles from readily available starting materials and catalysts. Finally, we will apply our method toward the syntheses of alkaloids goniomitine, aspidospermidine and galanthamine, and drug molecule FK-1052.