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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)620-625
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume27
Issue number3
DOIs
StatePublished - 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