Related Experiment Video
Updated: Apr 25, 2026
Enzymatic Synthesis of Epoxidized Metabolites of Docosahexaenoic, Eicosapentaenoic, and Arachidonic Acids
Published on: June 28, 2019
14,15-Epoxyeicosa-5,8,11-trienoic Acid (14,15-EET) surrogates: carboxylate modifications
John R Falck1, Sreenivasulu Reddy Koduru, Seetaram Mohapatra
1Departments of Biochemistry and Pharmacology, University of Texas Southwestern Medical Center , 5323 Harry Hines Boulevard, Dallas, Texas 75390, United States.
Abstract:
The cytochrome P450 eicosanoid 14,15-epoxyeicosa-5,8,11-trienoic acid (14,15-EET) is a powerful endogenous autacoid that has been ascribed an impressive array of physiologic functions including regulation of blood pressure. Because 14,15-EET is chemically and metabolically labile, structurally related surrogates containing epoxide bioisosteres were introduced and have become useful in vitro pharmacologic tools but are not suitable for in vivo applications. A new generation of EET mimics incorporating modifications to the carboxylate were prepared and evaluated for vasorelaxation and inhibition of soluble epoxide hydrolase (sEH). Tetrazole 19 (ED50 0.18 μM) and oxadiazole-5-thione 25 (ED50 0.36 μM) were 12- and 6-fold more potent, respectively, than 14,15-EET as vasorelaxants; on the other hand, their ability to block sEH differed substantially, i.e., 11 vs >500 nM. These data will expedite the development of potent and specific in vivo drug candidates.
Related Concept Videos
01:25Esters to Carboxylic Acids: Saponification
The reaction requires a base in stoichiometric amounts, which participates in the reaction and is not regenerated later. So, the base acts as a...
01:14Alkylation of β-Diester Enolates: Malonic Ester Synthesis
01:16IUPAC Nomenclature of Carboxylic Acids
For acyclic saturated monocarboxylic acids, the longest hydrocarbon chain containing the –COOH carbon is identified as the parent chain. Then, the last -e of the parent hydrocarbon name is replaced with a suffix -oic acid.
01:13Carboxylic Acids to Esters: Acid-Catalyzed (Fischer) Esterification Mechanism
01:28Structures of Carboxylic Acid Derivatives
Carboxylic acid derivatives contain an acyl group attached to a heteroatom such as chlorine, oxygen, or nitrogen. The carbonyl carbon and oxygen are both sp2-hybridized with an unhybridized p orbital.
The three sp2 orbitals of the carbonyl carbon form three σ bonds, one each with the carbonyl oxygen, the α carbon, and the heteroatom, whereas the other two sp2 orbitals of the carbonyl oxygen are occupied by the lone pairs. Further, the...
03:00Preparation of Epoxides
Epoxides result from alkene oxidation, which can be achieved by a) air, b) peroxy acids, c) hypochlorous acids, and d) halohydrin cyclization.
Epoxidation with Peroxy Acids
Epoxidation of alkenes via oxidation with peroxy acids involves the conversion of a carbon–carbon double bond to an epoxide using the oxidizing agent meta-chloroperoxybenzoic acid, commonly known as MCPBA. Since the O–O bond of peroxy acids is very weak, the addition of electrophilic oxygen of peroxy...