虎皮楠生物碱calyciphylline C, N 和 yunnandaphnine A 的不对称全合成研究

The daphniphyllum alkaloids are a large class of natural products isolated from the genus Daphniphyllum. Due to their complex and diverse structural skeletons and extensive biological activities, enormous synthetic efforts have been directed to daphniphyllum alkaloids. Based on the structural and biogenetic relationships between three kind of daphniphyllum alkaloids (yuzurimine-type, calyciphylline C-type and daphmanidin A-type), this project is aimed to develop an efficient and general synthetic strategy to quickly construct the [6/6/7/5/5]BCDEF pentacyclic skeleton of daphmanidin A-type alkaloids, which employs a sequential oxidative dearomatization/intramolecular Diels-Alder cycloaddition and a tandem SmI2-mediated deoxygenative reduction/Michael addition reaction as the key steps. From the pentacyclic intermediate, the asymmetric total synthsis of three daphniphyllum alkaloids (calyciphylline N, calyciphylline C and yunnandaphnine A) could be achieved through intramolecular aza-Wittig reaction, intramolecular Schmidt reaction and the followed ring-cleavege of azetidine/ ketalization, respectively.

虎皮楠生物碱是从交让木属植物中分离得到的一大类天然产物，因其具有复杂多样的骨架结构和广泛的生物活性，一直是合成领域的研究热点之一。基于对yuzurimine型、calyciphylline C型和daphmanidin A型三种虎皮楠生物碱的结构和生源关系的考虑，本项目拟发展一条高效通用合成策略：利用关键的氧化去芳化/分子内Diels-Alder环加成反应和SmI2介导的羰基邻位脱氧还原/Michael加成串联反应，快速构筑具有daphmanidin A型虎皮楠生物碱特征的[6/6/7/5/5]BCDEF五环骨架。在此基础上，分别通过分子内aza-Wittig反应、分子内Schmidt反应以及随后的氮杂环丁烷开环/缩酮化，完成三个虎皮楠生物碱calyciphylline N, calyciphylline C 和yunnandaphnine A的不对称全合成。

虎皮楠生物碱是从虎皮楠属植物中分离得到的一类生物碱成分，因其具有复杂多样的骨架结构和广泛的生物活性，一直是合成领域的研究热点之一。迄今已有24个该类天然产物被完成全合成。本项目基于对yuzurimine型、calyciphylline C型和daphmanidin A型三种虎皮楠生物碱的结构特点和生源关系的考虑，拟发展一条高效通用合成策略：利用关键的氧化去芳化/分子内Diels-Alder环加成反应和SmI2介导的羰基邻位脱氧还原/Michael加成串联反应，快速构筑具有daphmanidin A型虎皮楠生物碱特征的[6/6/7/5/5]BCDEF五环骨架。在此基础上，分别通过分子内aza-Wittig反应、分子内Schmidt反应以及随后的氮杂环丁烷开环/缩酮化，完成三个虎皮楠生物碱calyciphylline N, calyciphylline C 和yunnandaphnine A的不对称全合成。通过对氧化去芳化/分子内Diels-Alder环加成反应的不断探索，目前，我们已经完成了关键的[6/6/7/5] BCDE四环骨架的构筑，该四环骨架的成功构建为整个全合成工作奠定了非常重要的基础。后续，我们还要继续尝试F环的构建，争取实现calyciphylline C, N和yunnandaphnine A等虎皮楠生物碱的不对称全合成。