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Smoking mixtures containing cannabimimetic indoles may still be illegally sold in Russia. Although a method for their analysis is required for forensic toxicology authorities, the detection of synthetic cannabinoids is a complicated analytical task because of low anticipated concentrations in urine and the lack of in vivo data on their metabolism. Here, the urinary metabolites of 1-pentyl-3-(1-naphthoyl)indole (JWH-018) and a procedure for determining them in urine are reported. Using gas and high-performance liquid chromatography combined with tandem mass spectrometry, two main monohydroxylated metabolites were identified in urine. Based on differences in their electron ionization MS/MS spectra, it is supposed that one of them is formed by the hydroxylation of an indole ring and the other, by the hydroxylation of a pentyl side chain. The main metabolites are almost completely excreted as conjugates with glucuronic acid. The structure of minor metabolites was proposed. The parent compound was not detected in urine at a level of 50 pg/mL 12 h after administration. Keywords: JWH-018, synthetic cannabinoids, smoking mixtures, metabolism, GC/MS, HPLC/MS. DOI:10.1134/S1061934811130090, INTRODUCTION In the last two years, so-called smoking mixtures ('Spice' etc.), which contain synthetic cannabinoids, mainly 1-pentyl-3-(1-naphthoyl)indole (JWH-018), appeared on the market of many countries under the guise of fragrances. [...]

The kidney is a major site of systemic oxygen sensing, regulating blood erythrocyte and hence oxygen content by hypoxia-inducible erythropoietin (Epo) expression. A constant ratio between blood perfusion and oxygen consumption, a stable corticomedullary oxygen gradient, and a relatively low tissue [Po.sub.2] are the prerequisites for the function of renal Epo-producing and oxygen-sensing (REPOS) cells, which are located in the juxtamedullary cortex. In kidney disease, renal oxygen consumption is decreased, leading to an increase in [Po.sub.2], dysfunction of REPOS cells, and anemia. The molecular principles of cellular oxygen sensing have been elucidated in the last few years, and genetically altered mouse models as well as hereditary diseases causing erythrocytosis have clarified the oxygen-signaling cascade leading to increased Epo expression in REPOS cells. However, the consequences of a number of recently discovered factors for the regulation of oxygen signaling in REPOS cells are unclear, asking for novel cell culture models which might be hampered by the putative neuron-like nature of this enigmatic cell type. hypoxia; anemia; erythrocytosis; gene expression; kidney disease; Krebs cycle; reactive oxygen species; von Hippel-Lindau doi: 10.1152/ajprenal.00736.2009.

Research has been conducted on the antipyretic drug paracetamol. The oxidation chemistry of this drug with UV/H (sub)2 O (sub)2 system has been examined via various techniques including (super)15 N NMR analysis and the details are reported.

The authors discusses the research conducted on the hypoxia-inducible factor (HIF). The topics of interest include HIF control by prolyl hydroxylation, asparaginyl hydroxylation and HIF transactivation function, and therapeutic opportunities.

Research has been conducted on the brown-rot basidiomycetes. The utilization of benzaldehyde as the aromatic substrate for these basidomycetes has been carried out and the results have revealed benzylic oxidation and reduction.

Research has been conducted on the prostaglandins. The route to the F (sub)2t -isoprostanes has been developed via the use of C20 precursor's biomimetic radical cyclization and the results demonstrate the formation of (15R)- and (15S)-F (sub)2t -isoprostane diastereoisomers.

Research has been conducted on the racemates and 2-fluorocycloalkyl N-phenylcarbamates. The biohydroxylation of these compounds with Beauveria bassiana has been investigated and the results indicate the isolation of the diastereoisomeric product mixtures hydroxylated in the 4-position.

Research has been conducted on the hydrocarbon oxidation reaction mechanism. The use of the hybrid density functional method in studying the mechanism of this reaction is described.

Research has been conducted on the pyrrolidine based scaffold comprised of 2,5-dideoxy-2,5-imino-D-idaric acid. The development of this compound has been carried out and the results indicate that the peptide strand attachment to the carboxylic groups has led to the peptidomimetics.

Research has been conducted on the triple-labeled vitamin D and its hydroxylated and dihydroxylated metabolites. The synthesis of these isotope-labeled drug molecules has been carried out via the coupling of [9- (super)13C]-Grundmann's ketone with the labeled A ring enyne fragments and the NMR experiment on a model micellar system is discussed.

Research has been conducted on all-cis 2,3,4,5-substituted pyrrolidines. The enantioselective synthesis of these sterically congested pyrrolidines has been carried out from D- and L-serine and pyrrolidines' all-cis configuration has been established via the X-ray analysis.

Research has been conducted on the imonene-6-hydroxylase-mediated monoterpene olefin limonene hydroxylation. The regiochemistry and facial stereochemistry of this hydroxylation determined via the substrate absolute configuration are discussed.

Research has been conducted on the bicyclic 2-pyridone dipeptide mimetic. The preparation of this compound in the optically active form and the steps of the synthesis which include osmium-catalyzed asymmetric olefin dihydroxylation are described.

Research has been conducted on the N-benzylpyrrolidine. The hydroxylation of this compound has been carried out with the Sphingomonas sp. HXN-200 resting cells to produce N-benzyl-3-hydroxypyrrolidine and the results indicate that the change of the docking/protecting group in pyrrolidines improves the hydroxylation activity and enantioselectivity of the compound.

Research has been conducted on the fosfomycin, organophosphonic acid isolated from the Streptomyces fradiae fermentation broths. The synthesis of this fosfomycin has been carried out via the asymmetric dihydroxylation reaction of dibenzyl (E)-1-propenylphosphonate with the modified asymmetric dihydroxylation-mix-alpha-(x3) and the results are reported.

Research has been conducted on the cis-1,2-dihydrocatechol obtained by microbial dihydroxylation of bromobenzene. The conversion of this dihydrocatechol into the enantiomer of the cyclolysine-based marine natural product bengamide E is described.

Research has been conducted on the amino acids found in proteins and forming peptide antibiotics by specific oxidation at the beta carbon. The strategy in the peptide antibiotic biosynthesis has been developed and discussed.

Research has been conducted on the yeast Trichosporon mucoides grown on glucose or phenol. The ability of this yeast to transform biphenyl into mono-, di- and trihydroxylated derivatives hydroxylated on the aromatic rings has been investigated.

Research has been conducted on the catalysis of the p-hydroxybenzoate by p-hydroxybenzoate hydroxylase. The results of the oxygen transfer to p-hydroxybenzoate via C4a-hydroperoxide of the flavin are described.

The stereoselective synthesis of fluorinated analogues of (2S,3R)-(3,4-dihydroxyphenyl)serine has been carried out. The results of the aldol condensation of 3,4-dibenzyloxy-2-fluorobenxaldehyde and 4,5-dibenzyloxy-2-fluorobenxaldehyde with oxazolidinone are discussed.

Research has been conducted on the Wittig/dihydroxylation reactions. The improved strategy for the higher sugars synthesis by the Wittig/dihydroxylation of unprotected aldoses has been developed and the results are discussed.

Research has been conducted on (-)-wilkstromol, a bioactive alpha-hydroxylated lactone lignan. The synthesis of (-)-wilkstromol from natural malik acid via consecutive alkylation strategy is discussed.

Research has been conducted on the alpha,beta-unsaturated nitriles. Results indicate that these nitriles are readily synthesized by the chelation-controlled ring opening of epoxy, tetrahydrofuranyl and tetrahydropyranyl acetonitriles.

Research has been conducted on the CYP2C19, selective for the 4'-hydroxylation of S-mephenytoin. The critical amino acids that determine the specificity of the human CYP2C19 for S-mephenytoin 4'-hydroxylation have been identified by chimeras constructed to replace CYP2C9 portions with CYP2C19 via site-directing mutagenesis.

A major catabolic pathway for the gibberellins (GAs) is initiated by 2[Beta]-hydroxylation, a reaction catalyzed by 2-oxoglutarate-dependent dioxygenases. To isolate a GA 2[Beta]-hydroxylase cDNA clone we used functional screening of a cDNA library from developing cotyledons of runner bean (Phaseolus coccineus L.) with a highly sensitive tritium-release assay for enzyme activity. The encoded protein, obtained by heterologous expression in Escherichia coli, converted [GA.sub.9] to [GA.sub.51] (2[Beta]-hydroxy[GA.sub.9]) and [GA.sub.51]-catabolite, the latter produced from [GA.sub.51] by further oxidation at C-2. The enzyme thus is multifunctional and is best described as a GA 2-oxidase. The recombinant enzyme also 2[Beta]-hydroxylated other [C.sub.19]-GAs, although only [GA.sub.9] and [GA.sub.4] were converted to the corresponding catabolites. Three related cDNAs, corresponding to gene sequences present in Arabidopsis thaliana databases, also encoded functional GA 2-oxidases. Transcripts for two of the Arabidopsis genes were abundant in upper stems, flowers, and siliques, but the third transcript was not detected by Northern analysis. Transcript abundance for the two most highly expressed genes was lower in apices of the GA-deficient ga1-2 mutant of Arabidopsis than in wild-type plants and increased after treatment of the mutant with [GA.sub.3]. This up-regulation of GA 2-oxidase gene expression by GA contrasts GA-induced down-regulation of genes encoding the biosynthetic enzymes GA 20-oxidase and GA 3[Beta]-hydroxylase. These mechanisms would serve to maintain the concentrations of biologically active GAs in plant tissues.

Evidence has indicated that circulating adrenal steroid quantitites were significantly changed in patients with Alzheimer's disease (AD). Aside of 3[Beta]-sulfatation and 3[Beta]-acylations, levels of dehydroepiandrosterone (DHEA) result from production and metabolic transformation yields. 7[Alpha]-Hydroxylation of DHEA has been described in humans, and 7[Alpha]-hydroxy-DHEA may be responsible for the known antiglucocorticoid effects of DHEA. Using a negative ion fragmentometry method with gas chromatography/mass spectrometry on trifluoroacetate derivatives, we measured levels of free 7[Alpha]-hydroxy-DHEA as well as its sulfated conjugate and its fatty acid esters in serum of 10 female patients with AD and of 8 age-matched healthy control women. Free 7[Alpha]-hydroxy-DHEA levels in AD and controls were not significantly different (240.2 [+ or -] 37.2 pg/ml and 206.8 [+ or -] 21.6 pg/ml, respectively), but sulfate conjugate levels were significantly increased in AD (p = .01) (262 [+ or -] 24 and 145.4 [+ or -] 27.6, respectively) as well as fatty acid esters (p = .041) (65.7 [+ or -] 6.9 and 40.7 9.2, respectively). These results indicated that the total 7[Alpha]-hydroxy-DHEA produced was significantly increased in AD (p = .024) and may contribute to the disease-related disturbances of DHEA production and metabolism.

Research has been conducted on cis and trans substituted 4-tert-butoxycarbonyl cyclohexylglycines. The synthesis of these cyclohexylglycines has been carried out via vinyl styrene asymmetric aminohydroxylation and the results are described.