Prenylated β-diketones, two new additions to the family of biologically active Hypericum perforatum L. (Hypericaceae) secondary metabolites

Two novel beta-diketones, 2,6,9-trimethyl-8-decene-3,5-dione (A) and 3,7,10-trimethyl-9-undecene-4,6-dione (B), were identified from the renowned medicinal plant Hypericum perforatum L. The structures of beta-diketones A and B were corroborated by syntheses (4 steps starting from methyl acetoacetate, overall yields 30% and 23%, respectively). In solution, these beta-diketones predominantly exist as two rapidly interconverting beta-keto-enol tautomers. The structures of A and B show some common fragments with the molecules of hyperforin and adhyperforin, respectively, the acknowledged multi-target secondary metabolites from St. John's wort. It is therefore not surprising that A displayed a noteworthy biological activity profile as well (including brine shrimp toxicity, antinociceptive, antidepressant and acetylcholinesterase inhibitory activity). beta-Diketone A manifested the most outstanding potency as an acetylcholinesterase inhibitor with IC50 value of 1.51 mu M pointing again to the beta-keto-enol moiety as a promising lead structure for the development of drugs that could lessen symptoms of Alzheimer's disease (such as dementia, depression and pain).