(-)-石杉碱Q、(+)-石蒜碱B、(+)-石蒜碱C和(-)-4-表石蒜碱D的发散性全合成
Divergent Total Syntheses of (-)-Huperzine Q, (+)-Lycopladine B, (+)-Lycopladine C, and (-)-4-epi-Lycopladine D.
作者信息
Hong Benke, Hu Dachao, Wu Jinbao, Zhang Jing, Li Houhua, Pan Yingming, Lei Xiaoguang
机构信息
Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology, College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center and, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China.
State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Science, Guangxi Normal University, Guilin, 541004, China.
出版信息
Chem Asian J. 2017 Jul 4;12(13):1557-1567. doi: 10.1002/asia.201700364. Epub 2017 Jun 8.
We report herein our synthetic efforts towards the divergent syntheses of (-)-huperzine Q (1), (+)-lycopladine B (2), (+)-lycopladine C (3), and (-)-lycopladine D (4). The 10-step total synthesis of (-)-huperzine Q (1) and the first total syntheses of (+)-lycopladines B (2) and C (3) were accomplished through a series of cascade reactions. Our approach involved a Michael addition/aldol/intramolecular C-alkylation sequence to forge the 6/9 spirocycle ring, and this was followed by an ethylene-accelerated carbonyl-olefin metathesis to construct the common 6/5/9 ring system. Finally, late-stage enamine bromofunctionalization enabled us to access (-)-huperzine Q (1), (+)-lycopladine B (2), and (+)-lycopladine C (3), and a tandem C4-epimerization/retro-Claisen condensation furnished (-)-4-epi-lycopladine D (63).
我们在此报告了我们为实现（-）-石杉碱Q（1）、（+）-石蒜碱B（2）、（+）-石蒜碱C（3）和（-）-石蒜碱D（4）的发散合成所做的合成努力。通过一系列串联反应完成了（-）-石杉碱Q（1）的十步全合成以及（+）-石蒜碱B（2）和C（3）的首次全合成。我们的方法包括通过迈克尔加成/羟醛缩合/分子内C-烷基化序列构建6/9螺环，随后通过乙烯加速的羰基-烯烃复分解反应构建常见的6/5/9环系。最后，后期烯胺溴官能团化使我们能够得到（-）-石杉碱Q（1）、（+）-石蒜碱B（2）和（+）-石蒜碱C（3），而串联的C4-差向异构化/逆克莱森缩合反应则得到了（-）-4-表石蒜碱D（63）。
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