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Palladium mediated allylic Mitsunobu displacement : stereocontrolled synthesis of hepoxilin A3 and trioxilin A3 methyl esters

A regio- and stereoselective palladium mediated allylic displacement under Mitsunobu conditions was exploited for the preparation of several hepoxilin A3 and trioxilin A3 stereoisomers.

NADPH-dependent microsomal metabolism of 14,15-epoxyeicosatrienoic acid to diepoxides and epoxyalcohols

The arachidonic acid epoxygenase metabolite 14,15-epoxyeicosatrienoic acid is further metabolized by rat liver microsomal fractions to regioisomeric diepoxides and epoxyalcohols. Diepoxides result from epoxidation at the 5,6-, 8,9-, or 11,12-olefins. Hydroxylation leading to epoxyalcohols with a cis, trans-conjugated dienol occurs at carbons 5, 8, 9, or 12. Structural assignments were established by chromatographic and mass spectral comparisons with synthetic standards. The reaction requires NADPH and is inhibited by typical cytochrome P-450 inhibitors. Analysis of the time course of product formation during arachidonic acid oxidation by rat liver microsomal fractions indicated that all four regioisomeric epoxyeicosatrienoic acids can be further metabolized by the enzyme system.

Modified pyridinium chlorochromate oxidation of aldehydes to carbamoyl azides/acyl azides or carboxylic acids

Abstract Aldehydes are transformed into carbamoyl azides/acyl azides by pyridinium chlorochromate in the presence of sodium azide. Comparable oxidations modified with sodium cyanide generate carboxylic acids from simple aliphatic aldehydes whereas conjugated aldehydes are unreactive.

CHIRAL ACETALS : STEREOCONTROLLED SYNTHESES OF 16-,17-, AND 18-HYDROXYEICOSATETRAENOIC ACIDS, CYTOCHROME P-450 ARACHIDONATE METABOLITES

Chiral adducts from Grignard or allylsilane additions to 1,3-dioxan/1,3-dioxolan-4-ones were exploited for the total synthesis of the R− and S-isomers of the title eicosanoids.

Arachidonate epoxygenase: Total synthesis of both enantiomers of 8,9- and 11,12-epoxyricosatrienoic acid

Abstract Both enantiomers of the epoxygenase metabolites 8,9- and 11,12-epoxyeicosatrienoic acid (EET) were synthesized by a convergent strategy utilizing dimethyl D- or L-malate and erythrospecific epoxidation.

Enantiospecific total synthesis of 8- and 12-hydroxyeicosatetraenoic acid

Abstract The R- and S-isomers of 8- and 12-hydroxyeicosatetraenoic acid (8- and 12-HETE) were synthesized from dimethyl matate derived precursors.

Synthesis of trioxilin B3

Both C(10) diastereomers of trioxilin B3, presumed to be a mixture of 10(R/S), 11(R), 12(R)-trihydroxyeicosa-5(Z), 8(Z), 14(Z)-trienoic acids, were prepared from a carbohydrate derived precursor by Wittig homologation and Mitsunobu inversion.

Metabolism of 12(R)-hydroxy-5,8,10,14-eicosatetraenoic acid (12(R)-HETE) in corneal tissues: Formation of novel metabolites

12(R)-Hydroxy-5,8,10,14-eicosatetraenoic acid [12(R)-HETE], a cytochrome P450 arachidonate metabolite, is metabolized by corneal tissues via three distinct metabolic pathways: beta-oxidation, omega-hydroxylation, and keto-reduction. The major metabolite released from the intact rabbit corneal epithelium or cultured cells was identified by mass spectrometric analysis as 8-hydroxy-4,6,10-hexadecatrienoic acid, the tetranor metabolite derived following two steps of beta-oxidation from the carboxy terminus. The beta-oxidation pathway was expressed in both microsomes and mitochondria isolated from bovine corneal epithelium and was dependent on the addition of oxidizing equivalents. The major metabolite of 12(R)-HETE in subcellular fractions of bovine corneal epithelial cells was a dihydro compound, 12-hydroxy-5,8,14-eicosatrienoic acid (12-HETrE). This derivative is presumably formed by an oxidation of the hydroxyl group followed by two keto-reduction steps, since its formation was accompanied by the appearance of a keto metabolite identified as 12-oxo-5,8,14-eicosatrienoic acid. The omega-hydroxylation, in contrast to other cell types, was a minor route for 12(R)-HETE metabolism in these tissues. Since 12(R)-HETE has been implicated as a modulator of Na(+)-K(+)-ATPase activity and its related functions in ocular tissues, these findings raise the possibility that the newly described metabolites may be involved in regulating corneal functions. In addition, the presence of a keto reductase in the cornea may be of great importance following injury since 12(R)-HETrE resulting from 12(R)-HETE by this activity is a potent ocular proinflammatory compound.

Enantiospecific synthesis of 17- and 18-hydroxyeicosatetraenoic acids, cytochrome P450 arachidonate metabolites

Abstract The title bioactive eicosanoids were prepared from dimethyl L -malate by a convergent strategy exploiting the differential reactivity of ethereal dialkylcuprates towards tosylates versus bromides.

A concise synthesis of (R)-hydroxy-E,Z-diene fatty acids: preparation of 12(R)-hete, tetranor-12(R)-hete, and 13(R)-hode

Chiral E-enals derived from functionalized 2-deoxy-D-ribofuranoses by ylide-induced β-elimination were exploited for the synthesis of fatty acid metabolites containing the (R)-hydroxy-E,Z-diene subunit.