Total Synthesis of the Galbulimima Alkaloids Himandravine and GB17 Using Biomimetic Diels-Alder Reactions of Double Diene Precursors.
Total Synthesis of the Galbulimima Alkaloids Himandravine and GB17 Using Biomimetic Diels-Alder Reactions of Double Diene Precursors.
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DOI：
10.1021/jacs.5b07710
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发表时间：
2015-09-02
影响因子：
15
通讯作者：
Thomson RJ
中科院分区：
文献类型：
--
作者：
Larson RT;Pemberton RP;Franke JM;Tantillo DJ;Thomson RJ
通过一种常见的仿生策略，包括不寻常的双二烯含有线性前体的Diels-Alder反应，完成了对映体选择性的全合成himandravine和GB 17。双二烯前体，含有或缺乏C12取代基所需的生产GB 17或himandravine，分别，被发现进行狄尔斯-阿尔德反应，以提供区域异构体环加合物的混合物映射到替代的碳环框架himandravine和GB 17。计算研究表明，这些狄尔斯-阿尔德反应进行通过过渡态结构类似的能量，具有高度的bispericyclic字符和低水平的regioselectivity反应中观察到的竞争轨道相互作用和扭曲能量的结果。结合实验和计算结果提供了宝贵的见解的生物合成的Galulimima生物碱。
The enantioselective total syntheses of himandravine and GB17 were completed through a common biomimetic strategy involving Diels–Alder reactions of unusual double diene containing linear precursors. The double diene precursors, containing or lacking a C12 substituent as required to produce GB17 or himandravine, respectively, were found to undergo Diels–Alder reactions to afford mixtures of regioisomeric cycloadducts that map onto the alternative carbocyclic frameworks of both himandravine and GB17. Computational investigations revealed that these Diels–Alder reactions proceed via transition state structures of similar energy that have a high degree of bispericyclic character and that the low levels of regioselectivity observed in the reactions are a consequence of competing orbital interaction and distortion energies. The combined experimental and computational results provide valuable insights into the biosynthesis of the Galbulimima alkaloids.