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 | |
| 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
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
}
TY - JOUR
T1 - Chemical synthesis and biological evaluation of ω-hydroxy polyunsaturated fatty acids
AU - Hwang, Sung Hee
AU - Wagner, Karen
AU - Xu, Jian
AU - Yang, Jun
AU - Li, Xichun
AU - Cao, Zhengyu
AU - Morisseau, Christophe
AU - Lee, Kin Sing Stephen
AU - Hammock, Bruce D.
PY - 2017/2/1
Y1 - 2017/2/1
N2 - 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).
AB - 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).
KW - 20-HEPE
KW - 20-HETE
KW - 22-HDoHE
KW - Pain
KW - TRPV1
KW - ω-Hydroxy PUFA
UR - http://www.scopus.com/inward/record.url?scp=85008156040&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85008156040&partnerID=8YFLogxK
U2 - 10.1016/j.bmcl.2016.12.002
DO - 10.1016/j.bmcl.2016.12.002
M3 - Article
C2 - 28025003
AN - SCOPUS:85008156040
VL - 27
SP - 620
EP - 625
JO - Bioorganic and Medicinal Chemistry Letters
JF - Bioorganic and Medicinal Chemistry Letters
SN - 0960-894X
IS - 3
ER -