State Key Laboratory of Bioorganic & Natural Products Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Lu, Shanghai 200032, China.
J Am Chem Soc. 2022 Aug 24;144(33):15355-15362. doi: 10.1021/jacs.2c06738. Epub 2022 Aug 10.
The napelline-type alkaloids possess an azabicyclo[3.2.1]octane moiety and an -kaurane-type tetracyclic skeleton (6/6/6/5) along with varied oxidation patterns embedded in the compact hexacyclic framework. Herein, we disclose a divergent entry to napelline-type alkaloids that hinges on convergent assembly of the -kaurane core using a diastereoselective intermolecular Cu-mediated conjugate addition and subsequent intramolecular Michael addition reaction as well as rapid construction of the azabicyclo[3.2.1]octane motif via an intramolecular Mannich cyclization. The power of this strategy has been demonstrated through efficient asymmetric total syntheses of eight napelline-type alkaloids, including (-)-napelline, (-)-12--napelline, (+)-dehydronapelline, (+)-12--dehydronapelline, (-)-songorine, (-)-songoramine, (-)-acoapetaldine D, and (-)-liangshanone.
那皮林型生物碱具有一个氮杂双环[3.2.1]辛烷部分和一个 - 贝壳杉烷型四环骨架（6/6/6/5），以及在紧凑的六环骨架中嵌入的各种氧化模式。在此，我们披露了一种那皮林型生物碱的发散入口，它取决于使用非对映选择性的分子间 Cu 介导的共轭加成和随后的分子内迈克尔加成反应以及通过分子内曼尼希环化快速构建氮杂双环[3.2.1]辛烷基序来汇聚装配 - 贝壳杉烷核。该策略的威力已通过对八种那皮林型生物碱（包括（-）-那皮林、（-）-12--那皮林、（+）-脱水那皮林、（+）-12--脱水那皮林、（-）-songorine、（-）-songoramine、（-）-acoapetaldine D 和（-）-liangshanone）的高效不对称全合成得到了证明。
