State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering , Lanzhou University , Lanzhou 730000 , China.
State Key Laboratory of Chemical Oncogenomics and Key Laboratory of Chemical Genomics, Shenzhen Engineering Laboratory of Nano Drug Slow-Release , Shenzhen Graduate School of Peking University , Shenzhen 518055 , China.
J Am Chem Soc. 2019 May 1;141(17):7147-7154. doi: 10.1021/jacs.9b02362. Epub 2019 Apr 17.
The enantioselective total synthesis of cage-shaped alkaloid (+)-arboridinine is reported. The synthesis takes advantage of the stereoselective double-Mannich reaction to rapidly construct the aza[3.3.1]bicyclic core along with two quaternary stereocenters of the alkaloid. Key steps for the present synthesis include an enantioselective Michael addition establishing the original chiral center at C10 and intramolecular dearomative alkylation forging the cage-shaped ring system found in arboridinine, as well as creating the requisite quaternary carbon center at C3. The bridgehead hydroxyl moiety at C11 was installed through a late-stage cobalt-catalyzed decarboxylative acetoxylation reaction. This strategy enables a 14-step asymmetric total synthesis of (+)-arboridinine from the readily available starting materials with most of the transformations performed on the decagram scale.
报道了笼状生物碱（+）- Arboridinine 的对映选择性全合成。该合成利用立体选择性的双曼尼希反应，快速构建了具有两个季碳立体中心的氮杂[3.3.1]双环核心。本合成的关键步骤包括对映选择性迈克尔加成，在 C10 处建立原始手性中心，以及分子内去芳构化烷基化形成 Arboridinine 中发现的笼状环系统，以及在 C3 处创建所需的季碳中心。桥头羟基在 C11 上通过后期钴催化脱羧乙酰氧基化反应进行安装。该策略使从易得的起始原料出发，通过 14 步不对称全合成（+）- Arboridinine 成为可能，其中大部分转化都在 10 克规模上进行。
