Total Synthesis and Biological Evaluation of the Resveratrol-Derived Polyphenol Natural Products Hopeanol and Hopeahainol A

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• 作者：K. C. Nicolaou ; Qiang Kang ; T. Robert Wu ; Chek Shik Lim ; David Y.-K. Chen
• 刊名：Journal of the American Chemical Society
• 出版年：2010
• 出版时间：June 2, 2010
• 年：2010
• 卷：132
• 期：21
• 页码：7540-7548
• 全文大小：561K
• 年卷期：v.132,no.21(June 2, 2010)
• ISSN：1520-5126

文摘

The total synthesis and biological evaluation of the resveratrol-derived natural products hopeanol (2) and hopeahainol A (3) in their racemic and antipodal forms are described. The Friedel−Crafts-based synthetic strategy employed was developed from model studies that established the feasibility of constructing the C_7b quaternary center through an intramolecular Friedel−Crafts reaction and a Grob-type fragmentation to introduce an obligatory olefinic bond in the growing molecule. The final stages of the synthesis involved an epoxide substrate and an intramolecular Friedel−Crafts reaction, followed by oxidation to afford, upon global deprotection, hopeahainol A (3). The latter was converted under basic conditions to hopeanol (2), whereas the reverse transformation, previously suggested as a step in the biosynthesis of hopeahainol A (3), was not observed under a variety of conditions. Biological evaluation of the synthesized compounds confirmed the reported acetylcholinesterase inhibitory activity of hopeahainol A (3) but not the reported cytotoxic potencies of hopeanol (2).