[en] 11 alpha-Hydroxy-9,15-dioxo-2,3,4,5,20-pentanor-19-carboxyprostano ic acid (PGE-M) and 9 alpha,11 alpha-dihydroxy-15-oxo-2,3,4,5,20-pentanor-19-carboxyprostanoic acid (PGF-M) in urine were determined in an isotope dilution assay by gas chromatography/triple-stage quadrupole mass spectrometry. After addition of the 2H7-labeled internal standard, O-methylhydroxylamine hydrochloride in acetate buffer was added either directly (PGE-M) or after standing overnight at pH 10 (PGF-M) to form the methoxime. The sample was acidified to pH 2.5 and PGE-M and PGF-M were extracted with ethyl acetate/hexane. Then the prostanoids were derivatized to the pentafluorobenzyl ester and purified by thin-layer chromatography and the trimethylsilyl ether was formed. The products were quantified by gas chromatography/triple-stage quadrupole mass spectrometry. For PGE-M, the fragment ions m/z 349 and m/z 356 (2H7 standard) (daughter ions of m/z 637 and m/z 644 (2H7 standard)) were used. The results of the PGE-M assay were compared with those of an assay using the [2H3]methoxime as the internal standard. For determination of PGF-M, the daughter ions m/z 484 and m/z 491 (2H7 standard) with the parent ions m/z 682 and m/z 689 (2H7 standard) were chosen

[en] Dimethyl 3,4,5,6-[²H₄]-2-oxoheptylphosphonate was conveniently prepared in two steps from ethyl sorbate and used in a total synthesis of low-blank (≤0.2% ²H_o) 16,17,18,19-[²H₄]-prostaglandin D₂. The required allylic alcohol 15S was isolated by fractional crystallisation of the mixture of R/S epimers and then transformed to a key intermediate, 15S-silyloxy compound by regiocontrolled monosilylation of a diol. (author)

[en] An efficient synthesis of the analytically useful title compound 2c (1,1,3,3-(²H₄)-4-hydroxydebrisoquine sulphate), utilising a two-step deuteration(¹H/²H exchange of 3-nitromethylphthalide,4, and LiAl²H₄ reduction of 3,3-(²H ₂)-4-hydroxy-1,2,3,4-tetrahydroisoquinolin-1-one, 6), is described. (author)

[en] The synthesis of five 1,2,3,4-tetrahydroisoquinolines, which were either randomly labelled (1,1,3,3,4,4-²H₆), or regioselectively labelled (1,1-²H₂,2c; 3,3-²H₂, 2d; 4,4-²H₂), from isoquinoline, indan-2-one, and phenylacetonitrile is described. These deuterated bases were used in the preparation of labelled analogues of the antihypertensive agent debrisoquine. (author)

[en] Deuterated lipoxygenase and cyclooxygenase derivatives of eicosatetraenoic acid (arachidonic acid) and their metabolites are indispensable tools for organic trace analysis, biomedical studies, and mechanistic investigations on the corresponding endogenous (unlabelled) eicosanoids. Methods for the preparation of deuterated eicosanoids are reviewed. (author)

[en] An efficient preparation of the title compound (1a) starting from propargyl alcohol and proceeding via deuterated monomethyl adipate is described. As demonstrated by the first total synthesis of deuterated ω-carboxy-thromboxane B₂ 1a may serve as a versatile starting compound for the synthesis of various ω-carboxy prostanoic acid metabolites. (author)

[en] Kinetically controlled ¹H/²H exchange at carbon atom 5 of (-)-1,6-dehydrosparteinium monoperchlorate followed by sodium borohydride or sodium borodeuteride reduction of the iminium double bond gave optically active 5,5-(²H₂)-sparteine and 5,5,6-(²H₃)-sparteine, respectively. Under thermodynamic control a third deuterium atom was incorporated into 3 at carbon atom 7. Borohydride reduction or rapid re-exchange followed by reduction lead to the novel sparteine analogues 5,5,7-(²H₃)-sparteine and 7-(²H)-sparteine. The title compounds have been prepared in 76 to 83 % yield and 89 to 97 % isotopic purity. (author)

[en] The synthesis of the specifically labelled versatile prostaglandin intermediate 1b is described which involves the preparation of 2,2,3,3 (²H₄)butyliodide 6b via homogenous catalytic deuteration of the acetylene 4. Examples for the preparation of prostaglandins and extensive spectroscopic data are included. (author)

[en] 2,2,3,3-[²H₄]-1-Iodopentane was prepared in four steps from propargyl alcohol and used in the C-alkylation of the THP-protected 3-butyne-1-ol. Subsequent protective group removal, semi-deuteration of the acetylenic alcohol and further transformation by known methods afforded the labelled key reagent 3,4,6,6,7,7-[²H₆]-(Z)-(3-nonen-1-yl)triphenylphosphonium iodide. Wittig olefination of epoxy dienal with the ylide generated from the latter completed the convenient synthesis of hexadeuterated leukotriene A₄ methyl ester. (author)

[en] Thromboxane A2, the predominant product of arachidonic acid metabolism in the blood platelet, is a potent vasoconstrictor and platelet agonist. During its biosynthesis from cyclic endoperoxide, 12(S)-hydroxy-5Z,8E,10E-heptadecatrienoic acid (HHT) is formed in equal amounts. The further metabolism of HHT, catalyzed by 15-hydroxyprostaglandin dehydrogenase, leads to 12-oxo-5Z,8E,10E-heptadecatrienoic acid (Oxo-HT). Sample workup procedures are described which allow for the sensitive and reproducible determination of these two arachidonic acid metabolites in human plasma by gas chromatography-mass spectrometry in the presence of deuterated analogues as internal standards. HHT is derivatized to the pentafluorobenzyl ester tert-butyldimethylsilyl ether. In order to enable quantification of low concentrations of about 10 pg/ml in nonstimulated human plasma, the samples have to be purified by HPLC. Oxo-HT is derivatized to the pentafluorobenzyl ester, which is purified by HPLC, and then derivatized to the trimethylsilyloxime. The method allows quantification of Oxo-HT in concentrations down to 10 pg/ml plasma. The reported methods have been used to measure HHT and Oxo-HT in stimulated platelet rich plasma and to quantify HHT in nonstimulated plasma. Determination of endogenous levels of these two arachidonic acid metabolites may give new insights into the overall biosynthesis of thromboxane A2 in man