title: One-step semisynthesis of oleacein and the determination as a 5-lipoxygenase inhibitor.
abstract: The dialdehydes oleacein (2) and oleocanthal (4) are closely related to oleuropein (1) and ligstroside (3), the two latter compounds being abundant iridoids of Olea europaea. By exploiting oleuropein isolated from the plant leaf extract, an efficient procedure has been developed for a one-step semisynthesis of oleacein under Krapcho decarbomethoxylation conditions. Highlighted is the fact that 5-lipoxygenase is a direct target for oleacein with an inhibitory potential (IC50: 2 μM) more potent than oleocanthal (4) and oleuropein (1). This enzyme catalyzes the initial steps in the biosynthesis of pro-inflammatory leukotrienes. Taken together, the methodology presented here offers an alternative solution to isolation or total synthesis for the procurement of oleacein, thus facilitating the further development as a potential anti-inflammatory agent.
authors.affiliation: Division of Pharmacognosy and Natural Products Chemistry, Department of Pharmacy, University of Athens , Panepistimiopolis, GR-15771, Athens, Greece.
authors.forename: Konstantina
authors.initials: K
authors.lastname: Vougogiannopoulou
authors.forename: Christelle
authors.initials: C
authors.lastname: Lemus
authors.forename: Maria
authors.initials: M
authors.lastname: Halabalaki
authors.forename: Carlo
authors.initials: C
authors.lastname: Pergola
authors.forename: Oliver
authors.initials: O
authors.lastname: Werz
authors.forename: Amos B
authors.initials: AB
authors.lastname: Smith
authors.forename: Sylvie
authors.initials: S
authors.lastname: Michel
authors.forename: Leandros
authors.initials: L
authors.lastname: Skaltsounis
authors.forename: Brigitte
authors.initials: B
authors.lastname: Deguin
mesh_terms: D000447:Aldehydes / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism*; D000081004:Cyclopentane Monoterpenes; D005960:Glucosides / Q000378:metabolism; D006801:Humans; D057888:Iridoid Glucosides; D039823:Iridoids / Q000032:analysis / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D015394:Molecular Structure; D031658:Olea / Q000737:chemistry*; D010636:Phenols / Q000138:chemical synthesis* / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology; D018515:Plant Leaves / Q000378:metabolism; D011714:Pyrans / Q000378:metabolism
chemical_list: D000447:Aldehydes; D000893:Anti-Inflammatory Agents; D000081004:Cyclopentane Monoterpenes; D005960:Glucosides; D057888:Iridoid Glucosides; D039823:Iridoids; D016859:Lipoxygenase Inhibitors; D010636:Phenols; D010936:Plant Extracts; D011714:Pyrans; C578055:oleacein; C002769:oleuropein; C445380:ligstroside; C503534:oleocanthal; D001094:Arachidonate 5-Lipoxygenase