Rama K. Bhatt

Production of 3R-hydroxy-polyenoic fatty acids by the yeast Dipodascopsis uninucleata

Various fatty acids were fed to the yeast Dipodascopsis uninucleata UOFS Y 128, and the extracted samples were analyzed for the accumulation of 3-hydroxy metabolites with the help of electron impact gas chromatography-mass spectrometry. Fatty acids containing a 5Z,8Z-diene system (5Z,8Z,11Z-eicosatrienoic, 5Z,8Z,11Z,14Z-eicosatetraenoic, and 5Z,8Z,11Z,14Z,17Z-eicosapentaenoic acids) yielded the corresponding 3-hydroxy-all-Z-eicosapolyenoic acids. Moreover, linoleic acid (9Z,12Z-octadecadienoic acid) and 11Z,14Z,17Z-eicosatrienoic acid were converted to the 3-hydroxylated metabolites of shorter chain length, e.g., 3-hydroxy-5Z,8Z-tetradecadienoic acid and 3-hydroxy-5Z,8Z,11Z-tetradecatrienoic acid, respectively. In contrast, no accumulation of a 3-hydroxy metabolite was observed with oleic acid (9Z-octadecenoic acid), linolelaidic acid (9E,12E-octadecadienoic acid), γ-linolenic acid (6Z,9Z,12Z-octadecatrienoic acid), and eicosanoic acid as substrate. These findings pinpoint that the 3-hydroxylation of a fatty acid in Dipodascopsis uninucleata requires a 5Z,8Z-diene system either directly or following initial incomplete β-oxidation. Following analysis of the enantiomer composition, the arachidonic acid metabolite was identified as 3R-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid, which rules out a normal β-oxidation as biosynthetic route to this new class of oxylipins.

Enantiospecific total synthesis of a novel arachidonic acid metabolite 3-hydroxyeicosatetraenoic acid

Abstract The enantiomers R - and S -3-hydroxyeicosatetraenoic acid 11a, 11b were synthesized from coupling of a chiral aldehyde 7 with a Wittig salt 4 , which were derived from 2-deoxy-D-ribose and arachidonic acid, respectively.

Stereospecific α-alkoxystannane couplings with acyl chlorides: Total synthesis of (+)-goniofufurone

Abstract Stereospecific C-glycoside formation via Pd/Cu mediated coupling of PhCOCl with cyclic α-alkoxystannane 6 , derived from D -glucurono-6,3-lactone, was the key transformation in a concise total synthesis of the anticancer agent (+)-goniofufurone.

Detection of 20-hydroxyeicosatetrenoic acid in rat urine

20-Hydroxyeicosatetraenoic acid (20-HETE), an arachidonate metabolite of the cytochrome P450 omega hydroxylase, was detected in rat urine by gas chromatography-mass spectrometric techniques. The concentration of 20-HETE in urine from 7-week-old hypertensive and normotensive rats was 2.1 and 1.3 nM, respectively. This is the first demonstration of 20-HETE urinary excretion and thus calls attention to the possibility that 20-HETE participates in the regulation of renal function via its effect on vascular tone and ion transport processes.

C-Glycosides: Pd/Cu co-catalyzed thiocarboxylation of stannyl glucopyranosides

Abstract Stereospecific Pd/Cu co-catalyzed cross-couplings of tributylstannyl glucopyranosides with thiono- and thiolchloroformates afford good to excellent yields of C-glucosyl thiocarboxylates, versatile precursors for more complex C-glucoside homologs.

Palladium catalyzed cross-coupling and tandem cyclization-coupling of α-halo(thio)ethers with organotins

Abstract Pd(0) mediates the cross-coupling of organotins with a variety of α-haloethers/thioethers in moderate-good yields whereas an α-chloroacetoxyalkene failed to react. Tandem cyclization-coupling of the alkyl-palladium intermediate affords novel access to heterocycles.

Grignard additions to α,β-unsaturated dioxolanones: preparation of chiral allylic alcohols and protected α-hydroxy aldehydes

Abstract α,β-Unsaturated dioxolanones derived from mandelic acid smoothly add most Grignard reagents with good to excellent regio- and diastereoselectivities. The adducts are converted to chiral secondary alcohols by peroxidation at low temperature or to protected α-hydroxy aldehydes via ozonolysis.

Conjugate addition of α-alkoxystannanes via in situ transmetalation using catalytic CuCN

Abstract Catalytic CuCN mediates the in situ transrnetalation of α-thionocarbamoyl stannanes and subsequent conjugate addition to α,β-unsaturated carbonyls in the presence of chlorotrimethlysilane at or a little above room temperature.

Total synthesis of the ethanol inducible, proinflammatory autacoid 3(S)-hydroxy-leukotriene B4 (3-OH-LTB4) and analogues

Abstract 3(S)-Hydroxy-Leukotriene B 4 ( 1a ), its 3(R)-epimer 1b , and a 14,15-acetylenic analogue were efficiently prepared via chelation-controlled reduction of ketone 12 , obtained by acetylide addition to chiral β-hydroxylactones 7/9 .

Resolution of dihydroxyeicosanoates and of dihydroxyeicosatrienoates by chiral phase chromatography

A chromatographic method is described for the direct enantiomeric characterization of 5,6-, 8,9-, 11,12-, and 14,15-vic-dihydroxyeicosatrienoic acids (DHETs), metabolites of the cytochrome P-450 arachidonate epoxygenase pathway, and of their corresponding saturated vic-dihydroxyeicosanoic acids. Following esterification, the individual methyl or pentafluorobenzyl esters are resolved by chiral-phase chromatography utilizing a Chiralcel OC or OD column. This methodology will find analytical and preparative applications since it is simple and efficient and preserves, intact, the diol functionality.