State Key Laboratory of Bioorganic and Natural Products Chemistry, Center for Excellence in Molecular Synthesis , Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences , 345 Lingling Road , Shanghai 200032 , China.
Department of Phytochemistry, School of Pharmacy , Second Military Medical University , 325 Guohe Road , Shanghai 200433 , China.
J Am Chem Soc. 2018 Mar 28;140(12):4227-4231. doi: 10.1021/jacs.8b01681. Epub 2018 Mar 20.
Hybridaphniphylline B (1) is a Daphniphyllum alkaloid possessing 11 rings and 19 stereocenters. Here we report the first total synthesis of 1 featuring a late-stage intermolecular Diels-Alder reaction of a fully elaborated cyclopentadiene and asperuloside tetraacetate. The diene was prepared on the basis of a scalable route to daphnilongeranin B (4). Claisen rearrangement of an allyl dienol ether was exploited as a key step; the subtle variation of the substrate and use of protic solvents suppressed the undesired Cope rearrangement. Daphniyunnine E (6) and dehydrodaphnilongeranin B (7), two congeners of 4, were also synthesized. The dienophile arose from (+)-genipin through glycosylation and lactonization. A one-pot protocol was developed for the diene formation and Diels-Alder reaction; one of the cycloadducts was converted into 1 through reductive desulfurization and global deacetylation.
混合延胡索乙素 B（1）是一种拥有 11 个环和 19 个手性中心的紫堇科生物碱。在此，我们报告了 1 的首次全合成，其特征在于完全衍生的环戊二烯和asperuloside 四乙酸酯的晚期分子间 Diels-Alder 反应。该二烯基于 daphnilongeranin B（4）的可扩展路线制备。烯丙基二烯醇醚的 Claisen 重排被用作关键步骤；底物的细微变化和质子溶剂的使用抑制了不希望的 Cope 重排。Daphniyunnine E（6）和脱氢紫堇醇 B（7）是 4 的两种同系物，也被合成出来。亲二烯体来自（+）-栀子苷通过糖基化和内酯化。开发了一种一锅法用于二烯的形成和 Diels-Alder 反应；其中一个环加成物通过还原脱硫和全局脱乙酰化转化为 1。
