Syntheses of (-)-oleocanthal, a natural NSAID found in extra virgin olive oil, the (-)-deacetoxy-oleuropein aglycone, and related analogues.
Phenolic compounds extracted from extra virgin olive oil have attracted considerable recent attention. One of the components, (-)-oleocanthal (1), an inhibitor of the COX-1 and COX-2 enzymes, possesses similar potency as the NSAID ibuprofen. In this, a full account, we disclose the first- and now second-generation syntheses of both enantiomers of the oleocanthals, as well as the first synthesis of the closely related (-)-deacetoxy-oleuropein aglycone and a series of related analogues for structure activity studies. To demonstrate the utility of the second-generation synthesis, multigram quantities of (-)-oleocanthal were prepared in 10 steps (14% overall yield) from commercially available D-lyxose.
Smith
Amos B
AB
Department of Chemistry, Monell Chemical Senses Center and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. smithab@sas.upenn.edu
Sperry
Jeffrey B
JB
Han
Qiang
Q
D000447:Aldehydes / Q000138:chemical synthesis* / Q000737:chemistry; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry; D001688:Biological Products / Q000737:chemistry*; D002563:Cerium / Q000737:chemistry; D002712:Chlorides / Q000737:chemistry; D003500:Cyclization; D000081004:Cyclopentane Monoterpenes; D005030:Ethylenes / Q000737:chemistry; D057888:Iridoid Glucosides; D039823:Iridoids; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry; D015394:Molecular Structure; D000069463:Olive Oil; D010636:Phenols / Q000138:chemical synthesis* / Q000737:chemistry; D010938:Plant Oils / Q000737:chemistry*; D011714:Pyrans / Q000737:chemistry*
D000447:Aldehydes; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001688:Biological Products; D002712:Chlorides; D000081004:Cyclopentane Monoterpenes; D005030:Ethylenes; D057888:Iridoid Glucosides; D039823:Iridoids; D007659:Ketones; D000069463:Olive Oil; D010636:Phenols; D010938:Plant Oils; D011714:Pyrans; C002769:oleuropein; D002563:Cerium; C036216:ethylene; C503534:oleocanthal