title: Synthesis and evaluation of anti-inflammatory activity of derivatives of the marine natural products fuscol and eunicol.
abstract: The octocoral-derived terpenes fuscol and eunicol are known, potent anti-inflammatory agents. While total syntheses of one of the parent natural products have been published, the economic and practical feasibility of producing commercially viable amounts of material is very low. Based on the observation that the characteristic dienol of fuscol, eunicol and related compounds is conserved in anti-inflammatory activity, this project aimed to remove the structural complexity of the substituted cyclohexane and cyclodecadiene of fuscol and eunicol, respectively. The synthesis of a small panel of structurally simpler fuscol/eunicol analogues was completed and five of the six new compounds were found to have slightly superior activity to the parent natural products.
authors.affiliation: Nautilus Biosciences Canada, Inc., Duffy Research Centre, University of Prince Edward Island, 500 University Avenue, Charlottetown, PE C1A 4P3, Canada. Electronic address: rkerr@upei.ca.
authors.forename: Russell G
authors.initials: RG
authors.lastname: Kerr
authors.affiliation: St. Francis Xavier University, Physical Sciences Complex, 5009 Chapel Square, Antigonish, NS B2G 2W5, Canada.
authors.forename: Shawn
authors.initials: S
authors.lastname: Brophy
authors.affiliation: St. Francis Xavier University, Physical Sciences Complex, 5009 Chapel Square, Antigonish, NS B2G 2W5, Canada; University of Calgary, Department of Chemistry, 2500 University Drive NW, Calgary, AB T2N 1N4, Canada(†). Electronic address: dderksen@ucalgary.ca.
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Derksen
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000737:chemistry*; D004224:Diterpenes / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004423:Ear; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001688:Biological Products; D004224:Diterpenes; C000596292:eunicol; C000596291:fuscol; D013755:Tetradecanoylphorbol Acetate
keywords: Anti-inflammatory; Diterpene; Eunicol; Fuscol; Marine natural products; SAR study; Synthesis