The isolation, structural assignment, and biological properties of (–)-oleocanthal: a natural NSAID found in extra virgin olive oil

Phenolic compounds extracted from extra virgin olive oil have attracted wide attention since their discovery in the 1990's by Montedoro and co-workers. More recently (2003), Busch and co-workers at Unilever identified (–)-oleocanthal as the principle ingredient in high quality olive oils responsible for back of the throat irritation. We, in collaboration with the Monell Chemical Senses Center, reported the first- and second generation syntheses of both enantiomers of the oleocanthals, as well as the closely related (–)-decarbomethoxy-oleuropein aglycone and a series of related analogues for biological screening and structure activity studies. Natural oleocanthal was found to inhibit both the COX-1 and COX-2 enzymes, with potencies similar to the NSAID ibuprofen. Given that ibuprofen also possesses inhibitory effects on Aβ aggregation, (–)-oleocanthal was screened for and found to inhibit both Aβ aggregation and tau fibrillization, and as such holds promise as a potential lead for the treatment of Alzheimer's and other neurodegenerative diseases.