基于交叉脱氢偶联反应策略的akuammiline生物碱的集体合成研究

Akuammiline alkaloids, a family of intricate natural products, have received considerable attention from synthetic communities due to their inherent synthetic challenges and varying biological activity. The development of an approach toward the efficient establishment of ABDE ring systems of akuammiline alkaloids is greatly critical for the collective synthesis of these alkaloids. Basing on our preliminary results, we hope to develop a catalytic coupling of α-Csp3-H bonds of amines with Csp2-H bonds of indoles by using a cross-dehydrogenative coupling protocol to rapidly construct the ABDE frameworks. Meanwhile, we will attempt to utilize a substrate control to accomplish the stereoselective transformations. Subsequently, the collective syntheses of aspidophylline A (1), picrinine (2) and scholarisine A (3) will be completed at once through some transformations starting from the CDC products. The outcome of this proposal will provide a scientific groundwork for building natural product-like libraries which will be used in medicinal chemistry.

Akuammiline生物碱因具有广泛的生物活性和复杂的分子结构吸引了越来越多的的合成化学家的注意。发展一种高效的akuammiline生物碱的ABDE核心骨架的合成方法，进而实现akuammiline生物碱集体合成方法有着重要的意义。本课题拟通过吲哚C2位Csp2-H与N-α位Csp3-H的交叉脱氢偶联（CDC）反应构建C-C键的策略一步合成akuammiline生物碱的ABDE核心四环骨架。同时运用底物控制实现立体选择性的CDC关环反应。从CDC关环反应得到的ABDE四环骨架中间体出发，完成akuammiline生物碱aspidophylline A (1)、picrinine (2)和scholarisine A (3)的集体合成。为进一步开展akuammiline生物碱的 “类天然产物库”构建与活性评价奠定基础。

Akuammiline生物碱因具有广泛的生物活性和复杂的分子结构吸引了越来越多的的合成化学家的注意。发展一种高效的akuammiline生物碱的ABDE核心骨架的合成方法，进而实现akuammiline生物碱集体合成方法有着重要的意义。本课题发展了分子碘/氯胺盐和钴/过氧酸酯为催化氧化体系，相应地实现了吲哚的C2α-H区域选择性的酰胺化和酰氧化反应。随后我们从C-H酰胺化的四氢咔唑出发，经过N-炔丙基化、脱硅基、氧化以及分子内关环反应，高效的合成了akuammiline生物碱的ABDE核心四环骨架。为实现Akuammiline生物碱的集体合成，我们发展了碘催化的氧化环合反应快速合成5-(3-吲哚基)噁唑，碘催化的串联叠氮化-环化反应合成3a-叠氮基-吡咯吲哚啉以及游离基硼氢化和硅氢化合成α‑二氟化烷基硼和α‑二氟化烷基硅。

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