Preparation of the enantiomers of 19-epoxy docosahexaenoic acids and their 4-hydroxy derivatives

Kato, Tadahiro; Ishimatu, Takayuki; Aikawa, Akiko; Taniguchi, Kohji; Kurahashi, Takuma; Nakai, Tadashi

doi:10.1016/s0957-4166(00)00015-x

Cited by 7 publications

(2 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We also have developed a method for chemically accessing the antipodes [the (R,S) epoxides] of the epoxides produced by the enzyme. Both enantiomers of 3a have been previously accessed by enzymatic resolution of 19,20-EDP bromohydrins, followed by ring closure (59). Total synthesis has been used to prepare EEQs and EETs (20,60,61), but not EDPs.…”

Section: Discussionmentioning

confidence: 99%

Enzymatic synthesis and chemical inversion provide both enantiomers of bioactive epoxydocosapentaenoic acids

Cinelli

Yang

Scharmen

et al. 2018

Journal of Lipid Research

View full text Add to dashboard Cite

Epoxy PUFAs are endogenous cytochrome P450 (P450) metabolites of dietary PUFAs. Although these metabolites exert numerous biological effects, attempts to study their complex biology have been hampered by difficulty in obtaining the epoxides as pure regioisomers and enantiomers. To remedy this, we synthesized 19,20- and 16,17-epoxydocosapentaenoic acids (EDPs) (the two most abundant EDPs in vivo) by epoxidation of DHA with WT and the mutant (F87V) P450 enzyme BM3 from WT epoxidation yielded a 4:1 mixture of 19,20:16,17-EDP exclusively as (,) enantiomers. Epoxidation with the mutant (F87V) yielded a 1.6:1 mixture of 19,20:16,17-EDP; the 19,20-EDP fraction was ∼9:1 (,):(,), but the 16,17-EDP was exclusively the (,) enantiomer. To access the (,) enantiomers of these EDPs, we used a short (four-step) chemical inversion sequence, which utilizes 2-(phenylthio)ethanol as the epoxide-opening nucleophile, followed by mesylation of the resulting alcohol, oxidation of the thioether moiety, and base-catalyzed elimination. This short synthesis cleanly converts the (,)-epoxide to the (,)-epoxide without loss of enantiopurity. This method, also applicable to eicosapentaenoic acid and arachidonic acid, provides a simple, cost-effective procedure for accessing larger amounts of these metabolites.

show abstract

Section: Discussionmentioning

confidence: 99%

Enzymatic synthesis and chemical inversion provide both enantiomers of bioactive epoxydocosapentaenoic acids

Cinelli

Yang

Scharmen

et al. 2018

Journal of Lipid Research

View full text Add to dashboard Cite

show abstract

“…Only the 4E regioisomer is commercially available as methyl ester and can be used as GC reference, whereas in literature monotrans DHA isomers were analyzed by several authors after deodorization/isomerization reactions of DHA-rich oils, assaying various conditions of GC analysis but lacking a specific regioisomer assignment. ,,,, As far as the synthesis of the DHA monoepoxides is concerned, the classical epoxidation reaction can lead to these compounds, which are named epoxydocosapentaenoic acid (EDP). 4,5-EDP and 19,20-EDP were known ,− also due to their biological relevance as metabolites of cytochrome P450. , The strategy of the separation of the intermediate monoepoxide regioisomers was successful to unambiguously individuate the epoxidation of the double bond position, using mono- and bidimensional nuclear magnetic resonance (NMR) experiments. Consequently, after ring opening, dibromide formation and elimination from each monoepoxide regioisomer double bond was unequivocally established, thus allowing for the assignment of the corresponding peaks in the GC analysis.…”

Section: Introductionmentioning

confidence: 99%

Trans Lipid Library: Synthesis of Docosahexaenoic Acid (DHA) Monotrans Isomers and Regioisomer Identification in DHA-Containing Supplements

Menounou

Giacometti

Scanferlato

et al. 2018

Chem. Res. Toxicol.

View full text Add to dashboard Cite

Docosahexaenoic acid (DHA) is a semiessential polyunsaturated fatty acid (PUFA) for eukaryotic cells that is found in natural sources such as fish and algal oils and widely used as an ingredient for omega-3 containing foods or supplements. DHA effects are connected to its natural structure with six cis double bonds, but geometrical monotrans isomers can be formed during distillation or deodorization processes, as an unwanted event that alters molecular characteristics and annihilates health benefits. The characterization of the six monotrans DHA regioisomers is an open issue to address for analytical, biological, and nutraceutical applications. Here we report the preparation, separation, and first identification of each isomer by a dual approach consisting of the following: (i) the direct thiyl radical-catalyzed isomerization of cis-DHA methyl ester and (ii) the two-step synthesis from cis-DHA methyl ester via monoepoxides as intermediates, which are separated and identified by nuclear magnetic resonance spectroscopy, followed by elimination for the unequivocal assignment of the double bond position. This monotrans DHA isomer library with NMR and GC analytical characterization was also used to examine the products of thiyl-radical-catalyzed isomerization of a fish oil sample and to evaluate the trans isomer content in omega-3 containing supplements commercially available in Italy and Spain.

show abstract

ChemInform Abstract: Preparation of the Enantiomers of 19‐Epoxy Docosahexaenoic Acids and Their 4‐Hydroxy Derivatives.

et al. 2000

View full text Add to dashboard Cite

Preparation of the Enantiomers of 19-Epoxy Docosahexaenoic Acids and Their 4-Hydroxy Derivatives.-The preparation of epoxide (V), lactone (VII), and 4-hydroxy derivative (IX) (and their enantiomers) is based on the resolution of ester (II) by lipase PS and vinyl acetate in the presence of thiacrown ether TCT to give resolved ester (II) and acetate (IV), which are each converted by similar procedures to the above compounds. -(KATO,

show abstract

Preparation of the enantiomers of 19-epoxy docosahexaenoic acids and their 4-hydroxy derivatives

Cited by 7 publications

References 18 publications

Enzymatic synthesis and chemical inversion provide both enantiomers of bioactive epoxydocosapentaenoic acids

Enzymatic synthesis and chemical inversion provide both enantiomers of bioactive epoxydocosapentaenoic acids

Trans Lipid Library: Synthesis of Docosahexaenoic Acid (DHA) Monotrans Isomers and Regioisomer Identification in DHA-Containing Supplements

ChemInform Abstract: Preparation of the Enantiomers of 19‐Epoxy Docosahexaenoic Acids and Their 4‐Hydroxy Derivatives.

Contact Info

Product

Resources

About