Total Synthesis of the Galbulimima Alkaloids Himandravine and GB17 Using Biomimetic Diels鈥揂lder Reactions of Double Diene Precursors

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• 作者：Reed T. Larson ; Ryan P. Pemberton ; Jenna M. Franke ; Dean J. Tantillo ; Regan J. Thomson
• 刊名：Journal of the American Chemical Society
• 出版年：2015
• 出版时间：September 2, 2015
• 年：2015
• 卷：137
• 期：34
• 页码：11197-11204
• 全文大小：650K
• ISSN：1520-5126

文摘

The enantioselective total syntheses of himandravine and GB17 were completed through a common biomimetic strategy involving Diels鈥揂lder 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鈥揂lder 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鈥揂lder 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.