title: Chemical synthesis and biological evaluation of ω-hydroxy polyunsaturated fatty acids.
abstract: ω-Hydroxy polyunsaturated fatty acids (PUFAs), natural metabolites from arachidonic acid (ARA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were prepared via convergent synthesis approach using two key steps: Cu-mediated CC bond formation to construct methylene skipped poly-ynes and a partial alkyne hydrogenation where the presence of excess 2-methyl-2-butene as an additive that is proven to be critical for the success of partial reduction of the poly-ynes to the corresponding cis-alkenes without over-hydrogenation. The potential biological function of ω-hydroxy PUFAs in pain was evaluated in naive rats. Following intraplantar injection, 20-hydroxyeicosatetraenoic acid (20-HETE, ω-hydroxy ARA) generated an acute decrease in paw withdrawal thresholds in a mechanical nociceptive assay indicating pain, but no change was observed from rats which received either 20-hydroxyeicosapentaenoic acid (20-HEPE, ω-hydroxy EPA) or 22-hydroxydocosahexaenoic acid (22-HDoHE, ω-hydroxy DHA). We also found that both 20-HEPE and 22-HDoHE are more potent than 20-HETE to activate murine transient receptor potential vanilloid receptor1 (mTRPV1).
authors.affiliation: Department of Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Hwang
authors.affiliation: Department of Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Wagner
authors.affiliation: Jiangsu Provincial Key Laboratory of TCM Evaluation and Development, China Pharmaceutical University, 639, Longmian Ave, Jiangning District, Nanjing, Jiangsu 211198, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Jiangsu Provincial Key Laboratory of TCM Evaluation and Development, China Pharmaceutical University, 639, Longmian Ave, Jiangning District, Nanjing, Jiangsu 211198, PR China.
authors.forename: Xichun
authors.initials: X
authors.lastname: Li
authors.affiliation: Jiangsu Provincial Key Laboratory of TCM Evaluation and Development, China Pharmaceutical University, 639, Longmian Ave, Jiangning District, Nanjing, Jiangsu 211198, PR China.
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Christophe
authors.initials: C
authors.lastname: Morisseau
authors.affiliation: Department of Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA.
authors.forename: Kin Sing Stephen
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Department of Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA. Electronic address: bdhammock@ucdavis.edu.
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Hammock
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis* / Q000737:chemistry / Q000627:therapeutic use; D000818:Animals; D015118:Eicosapentaenoic Acid / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D006893:Hydroxyeicosatetraenoic Acids / Q000627:therapeutic use; D010146:Pain / Q000188:drug therapy; D017288:Pain Threshold; D051381:Rats; D050051:Transient Receptor Potential Channels / Q000819:agonists / Q000378:metabolism
chemical_list: D000700:Analgesics; D005231:Fatty Acids, Unsaturated; D006893:Hydroxyeicosatetraenoic Acids; D050051:Transient Receptor Potential Channels; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D015118:Eicosapentaenoic Acid
keywords: 20-HEPE; 20-HETE; 22-HDoHE; Pain; TRPV1; ω-Hydroxy PUFA