Total synthesis and biological evaluation of the resveratrol-derived polyphenol natural products hopeanol and hopeahainol A.
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).
Nicolaou
K C
KC
Chemical Synthesis Laboratory at Biopolis, Institute of Chemical and Engineering Sciences, Agency for Science, Technology and Research, 11 Biopolis Way, The Helios Block, 03-08, Singapore 138667. kcn@scripps.edu
Kang
Qiang
Q
Wu
T Robert
TR
Lim
Chek Shik
CS
Chen
David Y-K
DY
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001688:Biological Products / Q000138:chemical synthesis* / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005419:Flavonoids / Q000138:chemical synthesis* / Q000494:pharmacology; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000494:pharmacology; D010636:Phenols / Q000138:chemical synthesis* / Q000494:pharmacology; D059808:Polyphenols; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry*
D000970:Antineoplastic Agents; D001688:Biological Products; D002800:Cholinesterase Inhibitors; D005419:Flavonoids; D006576:Heterocyclic Compounds, 4 or More Rings; D010636:Phenols; D059808:Polyphenols; D013267:Stilbenes; C526863:hopeahainol A; C540974:hopeanol; D000077185:Resveratrol