Total Synthesis and Biological Evaluation of the Resveratrol-Derived Polyphenol Natural Products Hopeanol and Hopeahainol A
2010-06-02T00:00:00Z (GMT) by
The total synthesis and biological evaluation of the resveratrol-derived natural products hopeanol (<b>2</b>) and hopeahainol A (<b>3</b>) 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<sub>7b</sub> 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 (<b>3</b>). The latter was converted under basic conditions to hopeanol (<b>2</b>), whereas the reverse transformation, previously suggested as a step in the biosynthesis of hopeahainol A (<b>3</b>), was not observed under a variety of conditions. Biological evaluation of the synthesized compounds confirmed the reported acetylcholinesterase inhibitory activity of hopeahainol A (<b>3</b>) but not the reported cytotoxic potencies of hopeanol (<b>2</b>).