title: Synthesis of the 16S,17S-Epoxyprotectin Intermediate in the Biosynthesis of Protectins by Human Macrophages.
abstract: The n-3 polyunsaturated fatty acids act as substrates during the resolution phase of acute inflammation for the biosynthesis of specialized pro-resolving lipid mediators. One premier example is the C22-dihydroxy-polyunsaturated fatty acid protectin D1 (1). The human 15-lipoxygenase type I, via stereoselective processes and with docosahexaenoic acid as the substrate, enables the formation of this specialized pro-resolving lipid mediator. Herein, based on results from LC/MS-MS metabololipidomics, support is presented for the apprehended biosynthesis of 1 in human macrophages occurring via the intermediate 16S,17S-epoxyprotectin (5). Stereochemically pure 5 was obtained using the Katsuki-Sharpless epoxidation protocol, establishing the chirality at the C16 and C17 atoms, one Z-selective reduction, and E- and Z-stereoselective Wittig reactions. In addition, information on the nonenzymatic aqueous hydrolysis products and the half-life of 16S,17S-epoxyprotectin (5) is presented.
authors.affiliation: School of Pharmacy, Department of Pharmaceutical Chemistry, University of Oslo , PO Box 1068 Blindern, N-0316 Oslo, Norway.
authors.forename: Marius
authors.initials: M
authors.lastname: Aursnes
authors.affiliation: School of Pharmacy, Department of Pharmaceutical Chemistry, University of Oslo , PO Box 1068 Blindern, N-0316 Oslo, Norway.
authors.forename: Jørn E
authors.initials: JE
authors.lastname: Tungen
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts 02115, United States.
authors.forename: Romain A
authors.initials: RA
authors.lastname: Colas
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts 02115, United States.
authors.forename: Iliyan
authors.initials: I
authors.lastname: Vlasakov
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts 02115, United States.
authors.forename: Jesmond
authors.initials: J
authors.lastname: Dalli
authors.affiliation: Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital and Harvard Medical School , Boston, Massachusetts 02115, United States.
authors.forename: Charles N
authors.initials: CN
authors.lastname: Serhan
authors.affiliation: School of Pharmacy, Department of Pharmaceutical Chemistry, University of Oslo , PO Box 1068 Blindern, N-0316 Oslo, Norway.
authors.forename: Trond V
authors.initials: TV
authors.lastname: Hansen
mesh_terms: D018957:CD59 Antigens; D002384:Catalysis; D002853:Chromatography, Liquid; D004281:Docosahexaenoic Acids / Q000096:biosynthesis* / Q000737:chemistry; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: C000607238:16S,17S-epoxyprotectin; D018957:CD59 Antigens; D005231:Fatty Acids, Unsaturated; C487679:protectin D1; D004281:Docosahexaenoic Acids