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

5 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

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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

Cite this

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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10.1016/j.bmcl.2016.12.002