title: Total synthesis of the anti-inflammatory and pro-resolving lipid mediator MaR1n-3 DPA utilizing an sp(3) -sp(3) Negishi cross-coupling reaction.
abstract: The first total synthesis of the lipid mediator MaR1n-3 DPA (5) has been achieved in 12 % overall yield over 11 steps. The stereoselective preparation of 5 was based on a Pd-catalyzed sp(3) -sp(3) Negishi cross-coupling reaction and a stereocontrolled Evans-Nagao acetate aldol reaction. LC-MS/MS results with synthetic material matched the biologically produced 5. This novel lipid mediator displayed potent pro-resolving properties stimulating macrophage efferocytosis of apoptotic neutrophils.
authors.affiliation: School of Pharmacy, Department of Pharmaceutical Chemistry, University of Oslo, PO Box 1068 Blindern, 0316 Oslo (Norway).
authors.forename: Jørn Eivind
authors.initials: JE
authors.lastname: Tungen
authors.forename: Marius
authors.initials: M
authors.lastname: Aursnes
authors.forename: Jesmond
authors.initials: J
authors.lastname: Dalli
authors.forename: Hildur
authors.initials: H
authors.lastname: Arnardottir
authors.forename: Charles Nicholas
authors.initials: CN
authors.lastname: Serhan
authors.forename: Trond Vidar
authors.initials: TV
authors.lastname: Hansen
mesh_terms: D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002384:Catalysis; D004281:Docosahexaenoic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D008264:Macrophages / Q000187:drug effects; D013237:Stereoisomerism
chemical_list: D000893:Anti-Inflammatory Agents; D004281:Docosahexaenoic Acids
keywords: cross-coupling; inflammation; natural products; palladium; total synthesis