Total Synthesis of (-)-Canadine, (-)-Rotundine, (-)-Sinactine, and (-)-Xylopinine Using a Last-Step Enantioselective Ir-Catalyzed Hydrogenation
Total Synthesis of (-)-Canadine, (-)-Rotundine, (-)-Sinactine, and (-)-Xylopinine Using a Last-Step Enantioselective Ir-Catalyzed Hydrogenation
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DOI：
10.1021/acs.joc.1c00602
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发表时间：
2021-06-02
影响因子：
3.6
通讯作者：
Chen, Fener
中科院分区：
文献类型：
--
作者：
Li, Weijian;Jiang, Meifen;Chen, Fener
以二取代苯乙胺和二取代苯甲醛为起始原料，经三步不对称全合成了一组四氢原小檗碱生物碱（-）-坎那丁、（-）-罗通定、（-）-sinactine和（-）-木品宁。我们对这四种生物碱的合成利用了以下策略：在第一步中，我们通过完全连续的流程实现了仲胺盐酸盐的高效和可持续的合成;在第二步中，我们开发了Pictet-Spengler反应/Friedel-Crafts羟烷基化/脱水级联来构建二氢原小檗碱核心结构在最后一步中，Ir催化的对映选择性氢化用于在四氢原小檗碱生物碱的C-14位引入所需的立体化学。这项工作显着加快了整个四氢原小檗碱生物碱家族的不对称合成，以及更多样化的一组结构相关的非天然类似物。
A concise asymmetric total synthesis of a group of tetrahydroprotoberberine alkaloids, (-)-canadine, (-)-rotundine, (-)-sinactine, and (-)-xylopinine, has been accomplished in three steps from the commercially available corresponding disubstituted phenylethylamine and disubstituted benzaldehyde. Our synthesis toward these four alkaloids took advantage of the following strategy: in the first step, we achieved an efficient and sustainable synthesis of secondary amine hydrochlorides via a fully continuous flow; in the second step, we developed a Pictet-Spengler reaction/Friedel-Crafts hydroxyalkylation/dehydration cascade for the construction of the dihydroprotoberberine core structure (ABCD-ring); and in the last step, Ir-catalyzed enantioselective hydrogenation was employed for the introduction of the desired stereochemistry at the C-14 position in the tetrahydroprotoberberine alkaloids. This work significantly expedites the asymmetric synthesis of the entire tetrahydroprotoberberine alkaloid family as well as a more diverse set of structurally related non-natural analogues.