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

Sung Hee Hwang; Karen Wagner; Jian Xu; Jun Yang; Xichun Li; Zhengyu Cao; Christophe Morisseau; Kin Sing Stephen Lee; Bruce D. Hammock

doi:10.1016/j.bmcl.2016.12.002

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

Sung Hee Hwang, Karen Wagner, Jian Xu, Jun Yang, Xichun Li, Zhengyu Cao, Christophe Morisseau, Kin Sing Stephen Lee, Bruce D. Hammock

Entomology

Research output: Contribution to journal › Article

7 Scopus citations

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 C[sbnd]C 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).

Original language	English (US)
Pages (from-to)	620-625
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	27
Issue number	3
DOIs	https://doi.org/10.1016/j.bmcl.2016.12.002
State	Published - Feb 1 2017

Keywords

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

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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Hwang, S. H., Wagner, K., Xu, J., Yang, J., Li, X., Cao, Z., Morisseau, C., Lee, K. S. S., & Hammock, B. D. (2017). Chemical synthesis and biological evaluation of ω-hydroxy polyunsaturated fatty acids. Bioorganic and Medicinal Chemistry Letters, 27(3), 620-625. https://doi.org/10.1016/j.bmcl.2016.12.002

Chemical synthesis and biological evaluation of ω-hydroxy polyunsaturated fatty acids. / Hwang, Sung Hee; Wagner, Karen; Xu, Jian; Yang, Jun; Li, Xichun; Cao, Zhengyu; Morisseau, Christophe; Lee, Kin Sing Stephen; Hammock, Bruce D.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 27, No. 3, 01.02.2017, p. 620-625.

Research output: Contribution to journal › Article

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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 C[sbnd]C 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).",

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