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Bioorg Med Chem Lett. 2017 Feb 1;27(3):620-625. doi: 10.1016/j.bmcl.2016.12.002. Epub 2016 Dec 2.

Chemical synthesis and biological evaluation of ω-hydroxy polyunsaturated fatty acids.

Author information

1
Department of Entomology and Nematology, and UC Davis Comprehensive Cancer Center, University of California, Davis, One Shields Avenue, Davis, CA 95616, USA.
2
Jiangsu Provincial Key Laboratory of TCM Evaluation and Development, China Pharmaceutical University, 639, Longmian Ave, Jiangning District, Nanjing, Jiangsu 211198, PR China.
3
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.

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).

KEYWORDS:

20-HEPE; 20-HETE; 22-HDoHE; Pain; TRPV1; ω-Hydroxy PUFA

PMID:
28025003
PMCID:
PMC5584617
DOI:
10.1016/j.bmcl.2016.12.002
[Indexed for MEDLINE]
Free PMC Article

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