CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2008
Ekambaram Ganapathy
SUMMARY 1Naringenin is a flavanone that is believed to have many biological actions, including as an anti-oxidant, free radical scavenger and an antiproliferative agent. The global incidence of gastric carcinoma is increasing rapidly, more than for any other cancer. Therefore, in the present study, we tested the effects of naringenin on gastric carcinogenesis induced by N -methyl- N,-nitro- N -nitrosoguanidine (MNNG) and saturated sodium chloride (S-NaCl) in rats. 2Male Wistar rats were divided into five groups and treated over a period of 20 weeks as follows: (i) a control group given corn oil (1 mL/rat, p.o.) daily 20 weeks; (ii) 200 mg/kg, p.o., MNNG on Days 0 and 14 with S-NaCl (1 mL/rat) administered twice a week for the first 3 weeks; (iii) 200 mg/kg, p.o., MNNG on Days 0 and 14, with naringenin (200 mg/kg, p.o., daily) treatment for the entire 20 weeks; (iv) 200 mg/kg, p.o., MNNG on Days 0 and 14, with naringenin treatment (200 mg/kg, p.o., daily) initiated from 6 to 20 weeks; (v) 200 mg/kg, p.o., naringenin alone daily for 20 weeks. 3In Group II rats in which gastric cancer was inducted with MNNG and S-NaCl, there was a significant increase in hydrogen peroxide and lipid peroxidation levels, with decreases in reduced glutathione, oxidized glutathione, glutathione peroxidase, glutathione reductase and glucose 6-phosphate dehydrogenase. In addition, in Group II rats with gastric cancer, there were significant increases in the activity of cytochrome P450, cytochrome b5 and NADPH cytochrome c reductase, with concomitant decreases in the activity of the phase II enzymes glutathione S-transferase and UDP-glucuronosyl transferase. Naringenin treatment (Groups III and IV) restored enzyme activity to near control levels. 4These results indicate that naringenin has a chemopreventive action against MNNG-induced gastric carcinoma in experimental rats. [source]

INVOLVEMENT OF N -METHYL- d -ASPARTATE RECEPTORS and NITRIC OXIDE IN THE ROSTRAL VENTROMEDIAL MEDULLA IN MODULATING MORPHINE PAIN-INHIBITORY SIGNALS FROM THE PERIAQUEDUCTAL GREY MATTER IN RATS

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 7 2005
Kazem Javanmardi
SUMMARY 1.,Supraspinal opioid antinociception is mediated, in part, by connections between the periaqueductal grey (PAG) and the rostral ventromedial medulla (RVM). Morphine antinociception from the PAG is decreased by serotonin, N -methyl- d -aspartate (NMDA) and opioid receptor antagonists administered into the RVM. Because the brain isoform of nitric oxide synthase (NOS) is also prominent in the RVM, the present study was designed to evaluate the effects of microinjection of the non-selective NOS inhibitor NG -nitro- l -arginine methyl ester (l -NAME) and the non-competitive NMDA receptor antagonist MK-801 into the RVM on PAG morphine antinociception and their potential interactions, as measured by the tail-flick test. 2.,Rats were anaesthetized with sodium pentobarbital and then special cannulas were inserted stereotaxically into the RVM and PAG. After 1 week recovery, the effects of microinjection of MK-801 and l -NAME into the RVM and their interactions in altering PAG morphine (2.5 µg) antinociception elicited from the PAG were assessed. 3.,Mesencephalic morphine antinociception was significantly reduced after pretreatment with l -NAME (0.6,1.3 µmol) or MK-801 (0.8 nmol). The reduction in mesencephalic morphine antinociception when MK-801 (0.8 nmol) and l -NAME (1 µmol) were microinjected sequentially into the RVM was not significantly different from the effects of MK-801 (0.8 nmol) or l -NAME (1 µmol) administered alone. 4.,These data imply that NMDA receptors and nitric oxide production in the RVM modulate the transmission of opioid pain-inhibitory signals from the PAG. [source]

Selection and identification of bacterial strains with methyl- tert -butyl ether, ethyl- tert -butyl ether, and tert -amyl methyl ether degrading capacities

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 11 2008
Jessica Purswani
Abstract Nine bacterial strains isolated from two hydrocarbon-contaminated soils were selected because of their capacity for growth in culture media amended with 200 mg/L of one of the following gasoline oxygenates: Methyl- tert -butyl ether (MTBE), ethyl- tert -butyl ether (ETBE), and tert -amyl methyl ether (TAME). These strains were identified by amplification of their 16S rRNA gene, using fD1 and rD1 primers, and were tested for their capacity to grow and biotransform these oxygenates in both mineral and cometabolic media. The isolates were classified as Bacillus simplex, Bacillus drentensis, Arthrobacter sp., Acinetobacter calcoaceticus, Acinetobacter sp., Gordonia amicalis (two strains), Nocardioides sp., and Rhodococcus ruber. Arthrobacter sp. (strain MG) and A. calcoaceticus (strain M10) consumed 100 (cometabolic medium) and 82 mg/L (mineral medium) of oxygenate TAME in 21 d, respectively, under aerobic conditions. Rhodococcus ruber (strain E10) was observed to use MTBE and ETBE as the sole carbon and energy source, whereas G. amicalis (strain T3) used TAME as the sole carbon and energy source for growth. All the bacterial strains transformed oxygenates better in the presence of an alternative carbon source (ethanol) with the exception of A. calcoaceticus (strain M10). The capacity of the selected strains to remove MTBE, ETBE, and TAME looks promising for application in bioremediation technologies. [source]

Methyl- tert -hexyl ether and methyl- tert -octyl ether as gasoline oxygenates: Anticipating widespread risks to community water supply wells,

ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 11 2007
Jeff Snelling
Abstract The widespread contamination of groundwater resources associated with methyl- tert -butyl ether (MtBE) use has prompted a search for replacement oxygenates in gasoline. Among the alternatives currently under development are higher methyl- tert -alkyl ethers, notably methyl- tert -hexyl ether (MtHxE) and methyl- tert -octyl ether (MtOcE). As was the case with MtBE, the introduction of these ethers into fuel supplies guarantees their migration into groundwater resources. In the present study, a screening-level risk assessment compared predicted well water concentrations of these ethers to concentrations that might cause adverse effects. A physicochemical model which has been successfully applied to the prediction of MtBE concentrations in community water supply wells (CSWs) was used to predict well water concentrations of MtHxE and MtOcE. The results indicate that these ethers are likely to contaminate water supply wells at slightly lower levels than MtBE as a result of migrating from leaking underground fuel tanks to CSWs. Because very little data is available on the physicochemical and environmental properties of MtHxE and MtOcE, estimation methods were employed in conjunction with the model to predict well water concentrations. Model calculations indicated that MtHxE and MtOcE will be present in many CSWs at concentrations approaching the concentrations that have caused widespread public health concern for MtBE. Based on these results and the possibility that MtHxE and MtOcE are potential carcinogens, testing of the toxicological properties of these ethers is recommended before they are used to replace MtBE in gasoline. [source]

Voltage-Dependent Block of N -Methyl- d -Aspartate Receptors by the Novel Anticonvulsant Dibenzylamine, a Bioactive Constituent of l -(+)-,-Hydroxybutyrate

EPILEPSIA, Issue 10 2003
Sean D. Donevan
Summary:,Purpose: Previously we demonstrated that l -(+)-,-hydroxybutyrate (L-BHB), acetoacetate (ACA), acetone, and dibenzylamine (DBA) were anticonvulsant in an audiogenic seizure,susceptible model, and that DBA was a bioactive contaminant identified in commercial lots of L-BHB. In the present study, we asked whether these effects could be mediated by ionotropic glutamate or ,-aminobutyric acidA (GABAA) receptors. Methods: We studied the effects of both stereoisomers of BHB (as well as the racemate), ACA, and DBA on N -methyl- d -aspartate (NMDA), ,-amino-3-hydroxy-5methyl-4-isoxazole-proprionic acid (AMPA), and GABAA receptors in cultured rodent neocortical neurons by using whole-cell voltage-clamp recording techniques. Results: Only L-BHB and DBA exerted a concentration- and voltage-dependent block of NMDA-evoked currents, whereas none of the tested substrates affected AMPA- or GABA-activated currents. The kinetics of whole-cell block by L-BHB and DBA were similar, providing additional evidence that DBA is responsible for the anticonvulsant activity of L-BHB. Conclusions: BHB and ACA do not exert direct actions on GABAA or ionotropic glutamate receptors in cultured neocortical neurons. In addition, we provide additional evidence that DBA is responsible for the anticonvulsant activity of L-BHB, and that this action may be mediated in part by voltage-dependent blockade of NMDA receptors. [source]

Highly Efficient Fluorine-Promoted Intramolecular Condensation of Benzo[c]phenanthrene: A New Prospective on Direct Fullerene Synthesis

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 36 2009
Konstantin Yu.
Abstract Various functional groups have been tested as alternative promoters of the intramolecular condensation of benzo[c]phenanthrene under flash vacuum pyrolysis conditions. Methyl and fluorine functionalization were found to be promising approaches. Unexpectedly high selectivity was observed in the cyclization of fluorinated benzo[c]phenanthrenes. The mechanism for the condensation reaction and the advantages of fluorine as a promoter for the rational synthesis of fullerenes are discussed.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source]

Dynamic Enzymatic Kinetic Resolution of Methyl 2,3-Dihydro-1H -indene-1-carboxylate

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 35 2009
Jörg Pietruszka
Abstract A new reaction setup for kinetic enzymatic resolution was established and is demonstrated for the case of the hydrolase-catalysed conversion of methyl 2,3-dihydro-1H -indene-1-carboxylate (1) in conjunction with a base-catalysed racemisation. The system allows controlled racemisation, resulting in efficient dynamic kinetic resolution (DKR) of the title compound. Short reaction times and high enantioselectivities were obtained with CAL-B and TBD (1,5,7-triazabicyclo[4.4.0]dec-5-ene). Compound (R)- 1 (ee 95,%) served as a starting material in a domino reaction that led to the biaryl indanyl ketone (R)- 8, a lead compound for novel inhibitors of peptidyl-prolyl- cis/trans -isomerases, in 94,% ee. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source]

Regioselective C-6 Hydrolysis of Methyl O -Benzoyl-pyranosides Catalysed by Candida Rugosa Lipase

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 10 2009
Aslan Esmurziev
Abstract Hydrolysis of six methyl O -benzoyl-pyranosides has been investigated using Candida rugosa lipase in dioxane/buffer mixtures. The lipase catalysed the hydrolysis of all substrates in a regiospecific manner at C-6. The rate of reaction was dependent on pyranoside structure, reaction temperature and scale, dioxane concentration and agitation speed. Starting from their C-6 O -benzoyl precursors, the methyl 2,3,4-tri- O -benzoyl-pyranosides of ,- D -galactose, ,- D -galactose, ,- D -glucose, and methyl 2,3-di- O -benzoyl-,- D -galactopyranoside could be isolated in 85,96,% yield. In hydrolysis of methyl 2,3,4,6-tetra- O -benzoyl-,- D -glucopyranoside and methyl 2,3,4,6-tetra- O -benzoyl-,- D -galactopyranoside substrate inhibition were observed, which in part could be overcome by increasing the reaction volume. Methyl 2,3,4,6-tetra- O -benzoyl-,- D -glucopyranoside and methyl 2,3,4,6-tetra- O -benzoyl-,- D -mannopyranoside were poor substrates for Candida rugosa lipase and low degree of conversion towards products were obtained under all conditions. No acyl migration was detected in any of the products.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source]

On the Reactivity of C(sp3),H ,-Bonds: Oxygenation with Methyl(trifluoromethyl)dioxirane

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 3 2008
Rossella Mello
Abstract The reactivity of C,H ,-bonds of a series of 2-substituted adamantanes 2 towards methyl(trifluoromethyl)dioxirane (1) shows a consistent dependence on the electron-withdrawing ability, either inductive or by resonance, of the substituent. The results are interpreted in terms of the ability of the substrate molecule to delocalize the electronic perturbation of the reacting center at the beginning of the reaction path. The model shows that the electronic demand from the reacting C,H ,-bond is transmitted along the substrate through a chain of hyperconjugative interactions, the relative intensities of which depend on the ,-bonds involved. The substrate molecule simultaneously provides positive and negative stabilizing hyperconjugative interactions to the reacting center, their balance defining the geometry of the system at the beginning of the reaction path. The model constitutes a new experimental approach to measurement of the perturbation induced by substituents with significant resonance contributions on an adjacent C,H ,-bond. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source]

Synthesis and Glycosidase Inhibitory Activities of Pyrrolidines and Piperidines with N -(Polyhydroxyalkyl) Side Chains

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 18 2007
Sabrina Boutefnouchet
Abstract Amidification of L -proline (3) with (+)-(R,R)- 6 and (,)-(S,S)-tartaric anhydride diacetate (7) gave N -substituted L -proline derivatives 8a,b, respectively. Acids 8a,b were transformed into diesters 9a,b with MeOH/HCl. Similar reactions with methyl (2S,4R)- 4 and (2R,4S)-4-acetoxypipecolate (5) led to bicyclic lactams 14a,b and 15a. Compounds 8a,b were converted into N -(trihydroxybutyl)pyrrolidine derivatives 8c,d, 10a,b and 11a,b. Methyl (2S,4R)- 20a and (2R,4S)-4-acetoxy- N -[(2S,3S)-1,2,3-trihydroxybutyl]pipecolate (20b) were obtained by displacement of (,)-(2S,2S)-2- O -benzyl-3,4- O -isopropylidene-1-deoxy-1-iodothreitol (19) by 4 and 5. Compounds 20a,b were converted into (2S,4R,2,S,2,S)- 21a and(2R,4S,2,S,3,S)-4-hydroxy-2-hydromethyl- N -(2-benzyloxy-3,4-isopropylidenedioxy)piperidine (21b) and finally into unprotected pentols 22a,b. Nonprotected (2S,2,S,3,S)- 11a and (2S,2,R,3,R)- N -(1,2,3-trihydroxybutyl)prolinol (11b), as well as 22a,b, did not inhibit any of the 13 glycosidases assayed. However, a triacetoxy derivative, (2S,3S)-2,3-diacetoxy-4-[(2R,4S)-4-acetoxy-2-(methoxycarbonyl)piperidin-1-yl]-4-oxobutanoic acid (13b) is an inhibitor (IC50 = 157 ,M) of ,- L -fucosidase from bovine kidney.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source]

Facile and Selective Synthesis of 4-Methyl- and 4-Phenylthiosemicarbazide (=N -Methyl- and N -Phenylhydrazinecarbothioamide) Derivatives of Benzil (=1,2-Diphenylethane-1,2-dione)

HELVETICA CHIMICA ACTA, Issue 11 2007
David
Abstract A selective synthesis of 4-methylthiosemicarbazide (=N -methylhydrazinecarbothioamide; 4a) derivatives by reaction with benzil (=1,2-diphenylethane-1,2-dione; 3) is described. The reaction conditions determined the condensation product formed. The most important factor was the acid used: in the presence of conc. HCl solution, the open-chain 2,:,1 compound 1a was exclusively obtained, whereas in the presence of 2M HCl, the cyclic 1,:,1 condensation product 2a was formed. The alcohol used, the presence of H2O, and the time of heating were additional crucial factors. The new cyclic compound 2a with a MeO group was exclusively formed when working under high-dilution conditions. The reaction with the 4-phenyl derivative 4b gave new cyclic compounds as the major products under all conditions used (Scheme). [source]

Effective Methods for the Synthesis of N -Methyl , -Amino Acids from All Twenty Common , -Amino Acids Using 1,3-Oxazolidin-5-ones and 1,3-Oxazinan-6-ones

HELVETICA CHIMICA ACTA, Issue 11 2006
Andrew
Abstract N -Methyl , -amino acids are generally required for application in the synthesis of potentially bioactive modified peptides and other oligomers. Previous work highlighted the reductive cleavage of 1,3-oxazolidin-5-ones to synthesise N -methyl , -amino acids. Starting from , -amino acids, two approaches were used to prepare the corresponding N -methyl , -amino acids. First, , -amino acids were converted to N -methyl , -amino acids by the so-called ,1,3-oxazolidin-5-one strategy', and these were then homologated by the Arndt,Eistert procedure to afford N -protected N -methyl , -amino acids derived from the 20 common , -amino acids. These compounds were prepared in yields of 23,57% (relative to N -methyl , -amino acid). In a second approach, twelve N -protected , -amino acids could be directly homologated by the Arndt,Eistert procedure, and the resulting , -amino acids were converted to the 1,3-oxazinan-6-ones in 30,45% yield. Finally, reductive cleavage afforded the desired N -methyl , -amino acids in 41,63% yield. One sterically congested , -amino acid, 3-methyl-3-aminobutanoic acid, did give a high yield (95%) of the 1,3-oxazinan-6-one (65), and subsequent reductive cleavage gave the corresponding AIBN-derived N -methyl , -amino acid 61 in 71% yield (Scheme,2). Thus, our protocols allow the ready preparation of all N -methyl , -amino acids derived from the 20 proteinogenic , -amino acids. [source]

Transformations of Methyl 2-[(E)-2-(Dimethylamino)-1-(methoxycarbonyl)ethenyl]-1-methyl-1H -indole-3-carboxylate

HELVETICA CHIMICA ACTA, Issue 11 2006
David Bevk
Abstract A simple and efficient synthesis of novel 2-heteroaryl-substituted 1H -indole-2-carboxylates and , -carbolines, compounds 1,3, from methyl 2-(2-methoxy-2-oxoethyl)-1-methyl-1H -indole-3-carboxylate (4) by the enaminone methodology is presented. [source]

Highly Efficient Chemoenzymatic Synthesis of Methyl (R)- o -Chloromandelate, a Key Intermediate for Clopidogrel, via Asymmetric Reduction with Recombinant Escherichia coli

ADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 13 2008
Tadashi Ema
Abstract Methyl (R)- o -chloromandelate [(R)- 1], which is an intermediate for a platelet aggregation inhibitor named clopidogrel, was obtained in >99% ee by the asymmetric reduction of methyl o -chlorobenzoylformate (2) with recombinant Escherichia coli overproducing a versatile carbonyl reductase. A remarkable temperature effect on productivity was observed in the whole-cell reduction of 2, and the optimum productivity as high as 178,g/L was attained at 20,°C on a 2-g scale (1.0,M). The optimized reaction could be scaled up easily to transform 20,g of 2 in 100,mL of buffer. Three synthetic methods for 2 are compared. [source]

Reduction in glutamate uptake is associated with extrasynaptic NMDA and metabotropic glutamate receptor activation at the hippocampal CA1 synapse of aged rats

AGING CELL, Issue 5 2010
Brigitte Potier
Summary This study aims to determine whether the regulation of extracellular glutamate is altered during aging and its possible consequences on synaptic transmission and plasticity. A decrease in the expression of the glial glutamate transporters GLAST and GLT-1 and reduced glutamate uptake occur in the aged (24,27 months) Sprague,Dawley rat hippocampus. Glutamatergic excitatory postsynaptic potentials recorded extracellularly in ex vivo hippocampal slices from adult (3,5 months) and aged rats are depressed by DL-TBOA, an inhibitor of glutamate transporter activity, in an N -Methyl- d- Aspartate (NMDA)-receptor-dependent manner. In aged but not in young rats, part of the depressing effect of DL-TBOA also involves metabotropic glutamate receptor (mGluRs) activation as it is significantly reduced by the specific mGluR antagonist d-methyl-4-carboxy-phenylglycine (MCPG). The paired-pulse facilitation ratio, a functional index of glutamate release, is reduced by MCPG in aged slices to a level comparable to that in young rats both under control conditions and after being enhanced by DL-TBOA. These results suggest that the age-associated glutamate uptake deficiency favors presynaptic mGluR activation that lowers glutamate release. In parallel, 2 Hz-induced long-term depression is significantly decreased in aged animals and is fully restored by MCPG. All these data indicate a facilitated activation of extrasynaptic NMDAR and mGluRs in aged rats, possibly because of an altered distribution of glutamate in the extrasynaptic space. This in turn affects synaptic transmission and plasticity within the aged hippocampal CA1 network. [source]

Methyl 3-[3,,4,-(methylenedioxy)phenyl]-2-methyl glycidate: An Ecstasy Precursor Seized in Sydney, Australia

JOURNAL OF FORENSIC SCIENCES, Issue 4 2007
Michael Collins Ph.D.
Abstract:, Five 44 gallon drums labeled as glycidyl methacrylate were seized by the Australian Customs Service and the Australian Federal Police at Port Botany, Sydney, Australia, in December 2004. Each drum contained a white, semisolid substance that was initially suspected to be 3,4-methylenedioxymethylamphetamine (MDMA). Gas chromatography,mass spectroscopy (GC/MS) analysis demonstrated that the material was neither glycidyl methacrylate nor MDMA. Because intelligence sources employed by federal agents indicated that this material was in some way connected to MDMA production, suspicion fell on the various MDMA precursor chemicals. Using a number of techniques including proton nuclear magnetic resonance spectroscopy (1H NMR), carbon nuclear magnetic resonance spectroscopy (13C NMR), GC/MS, infrared spectroscopy, and total synthesis, the unknown substance was eventually identified as methyl 3-[3,,4,(methylenedioxy)phenyl]-2-methyl glycidate. The substance was also subjected to a published hydrolysis and decarboxylation procedure and gave a high yield of the MDMA precursor chemical, 3,4-methylenedioxyphenyl-2-propanone, thereby establishing this material as a "precursor to a precursor." [source]

Study on the reaction of methyl N -Methyl- N -(6-substituted-5-nitropyrimidin-4-yl)glycinates with sodium alkoxides

JOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 2 2006
Inga Susvilo
Methyl N -methyl- N -(6-substituted-5-nitropyrimidin-4-yl)glycinates (4a-n), obtained from 6-substituted-4-chloro-5-nitropyrimidines and sarcosine methyl ester (methyl 2-(methylamino)acetate), in the reaction with sodium alkoxides underwent transformations to give different products. N -methyl- N -(5-nitropyrimidin-4-yl)glycinates (4a,i,j) bearing amino and arylamino groups in the position 6 of the pyrimidine ring gave corresponding 6-substituted-4-methylamino-5-nitrosopyrimidines (5a,i,j). In the reaction of N -(6-alkylamino-5-nitropyrimidin-4-yl)- N -methylglycinates (4b,f-h) with sodium alkoxides the corresponding 6-alkylamino-4-methylamino-5-nitrosopyrimidines (5b,f-h) and 5-hydroxy-8-methyl-5,8-dihydropteridine-6,7-diones (6b,f-h) were formed. The main products of the reaction of N -(6-dialkylamino-5-nitropyrimidin-4-yl)- N -methylglycinates (4c-e,k,l), after work-up, were the corresponding 6-dialkylamino-9-methylpurin-8-ones (7c-e,k,l) and 8-alkoxy-6-dialkylamino-9-methylpurines (9c,1,10c,l). Methyl N -methyl- N -{[6-(2-methoxy-oxoethyl)thio]-5-nitropyrimidin-4-yl}glycinate (4n) under the same conditions gave methyl 7-methylaminothiazolo[5,4- d]pyrimidine-2-carboxylate (13). Mechanisms of the observed transformations are discussed. [source]

Synthesis of morphine-[N -methyl- 14C]-6- , - D -glucuronide

JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 2 2002
John R. Ferguson
Abstract Protected morphine-6-glucuronide was converted into morphine-[N -methyl- 14C]-6-glucuronide by a three-step procedure. Methyl (3-pivaloylmorphin-6-yl 2,3,4-tri- O -isobutyryl- , -D-glucopyranosid)uronate was N-demethylated by treatment with 1-chloroethyl chloroformate to afford protected normorphine-6-glucuronide as its hydrochloride salt. The normorphine-6-glucuronide derivative was alkylated with iodomethane-[14C] in the presence of potassium carbonate to produce C-14 labelled protected morphine-6-glucuronide. Finally, hydrolysis of the protecting groups using 5% sodium hydroxide solution gave morphine-[N -methyl- 14C]-6- , -D-glucuronide with a specific activity of 41.8 mCi mmol,1 and radiochemical purity of 99.2% (HPLC). Copyright © 2002 John Wiley & Sons, Ltd. [source]

Rosiglitazone maleate (BRL 49653-C); the preparation of [14C] and [3H] isotopomers

JOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 5 2001
Tabassum Kirefu
Abstract The glitazone insulin sensitisers are an important class of pharmaceuticals for the treatment of Type 2 diabetes. Syntheses of [methyl - 14C] and [3H]rosiglitazone maleate (BRL 49653-C), marketed by SmithKline Beecham Pharmaceuticals as Avandia® are described. [Methyl - 14C]BRL 49653-C was prepared in 5 steps in 12.6% overall radiochemical yield from K[14C]CN. Catalytic reduction with tritium gas of a dibromo derivative gave [3H]rosiglitazone with a specific activity of 58Ci/mmol. Copyright © 2001 John Wiley & Sons, Ltd. [source]

The synthesis of oligomers of oxetane-based dipeptide isosteres derived from L -rhamnose or D -xylose

JOURNAL OF PEPTIDE SCIENCE, Issue 6 2005
Stephen W. Johnson
Abstract Routes to oligomers (dimers, tetramers, hexamers) of five oxetane-based dipeptide isosteres have been established. Methyl 2,4-anhydro-5-azido-5-deoxy- L -rhamnonate ,monomer' led, by coupling the corresponding carboxylic acid and amine, to a ,dimer'. Reverse-aldol ring-opening occurred on attempted saponification of the dimer, so all further oligomerization was performed using TBDMS C-3 hydroxyl protection. The silyl protected L -rhamnonate monomer led in turn to the dimer (via the monomer acid and amine), the tetramer (via the dimer acid and amine) and finally the hexamer (via the tetramer acid and dimer amine). In each case the acids were obtained through saponification of the respective methyl esters and the amines were obtained by hydrogenation of the azides; coupling was TBTU-mediated. Essentially the same strategy was employed on equivalent D -lyxonate, 6-deoxy- L -altronate, 6-deoxy- D -gulonate and D -fuconate dipeptide isosteres to give the respective dimers, tetramers and hexamers. Copyright © 2004 European Peptide Society and John Wiley & Sons, Ltd. [source]

Hippocampal N -Methyl- d -Aspartate Receptor Subunit Expression Profiles in a Mouse Model of Prenatal Alcohol Exposure

ALCOHOLISM, Issue 2 2010
Sabrina L. Samudio-Ruiz
Background:, Although several reports have been published showing prenatal ethanol exposure is associated with alterations in N -methyl- d- aspartate (NMDA) receptor subunit levels and, in a few cases, subcellular distribution, results of these studies are conflicting. Methods:, We used semi-quantitative immunoblotting techniques to analyze NMDA receptor NR1, NR2A, and NR2B subunit levels in the adult mouse hippocampal formation isolated from offspring of dams who consumed moderate amounts of ethanol throughout pregnancy. We employed subcellular fractionation and immunoprecipitation techniques to isolate synaptosomal membrane- and postsynaptic density protein-95 (PSD-95)-associated pools of receptor subunits. Results:, We found that, compared to control animals, fetal alcohol-exposed (FAE) adult mice had: (i) increased synaptosomal membrane NR1 levels with no change in association of this subunit with PSD-95 and no difference in total NR1 expression in tissue homogenates; (ii) decreased NR2A subunit levels in hippocampal homogenates, but no alterations in synaptosomal membrane NR2A levels and no change in NR2A-PSD-95 association; and (iii) no change in tissue homogenate or synaptosomal membrane NR2B levels but a reduction in PSD-95-associated NR2B subunits. No alterations were found in mRNA levels of NMDA receptor subunits suggesting that prenatal alcohol-associated differences in subunit protein levels are the result of differences in post-transcriptional regulation of subunit localization. Conclusions:, Our results demonstrate that prenatal alcohol exposure induces selective changes in NMDA receptor subunit levels in specific subcellular locations in the adult mouse hippocampal formation. Of particular interest is the finding of decreased PSD-95-associated NR2B levels, suggesting that synaptic NR2B-containing NMDA receptor concentrations are reduced in FAE animals. This result is consistent with various biochemical, physiological, and behavioral findings that have been linked with prenatal alcohol exposure. [source]

Intramolecular charge delocalization and nonlinear optical properties of Methyl 3-(4-methoxy phenyl) prop-2-enoate from vibrational spectra

LASER PHYSICS LETTERS, Issue 7 2005
D. Sajan
Abstract The density functional computations of MMP are performed at B3LYP/6-31G (d,p) level to derive equilibrium geometry, vibrational wavenumbers and intensities, and first hyperpolarizability. Large NLO efficiency predicted for the first time in this new class of compounds has been confirmed by powder efficiency experiments. DFT calculation reveals that endocyclic angle at the junction of the propenoate group and the phenyl ring is decreased from 120° by 2.5°, whereas two neighbouring angles around the ring are increased by 2.1° and 1.2° respectively, associated with intramolecular charge transfer interaction. The vibrational spectra confirm the charge transfer interaction between ,COOCH3 group and phenyl ring through the ethylenic bridge with simultaneous infrared and Raman activation of C7=C18 stretching and ring modes 8 and 19. The large intensity differences observed between 8a and 8b modes in both IR and Raman spectrum due to the algebraic difference of the electronic effects of the substitutents have been discussed. The charge transfer interaction between ,COOCH3 group and phenyl ring through the ethylenic bridge resulting in , -electron cloud movement from donor to acceptor can make the molecule highly polarized and must be responsible for the NLO activity of MMP. (© 2005 by Astro, Ltd. Published exclusively by WILEY-VCH Verlag GmbH & Co. KGaA) [source]

Biofumigation: environmental impacts on the biological activity of diverse pure and plant-derived isothiocyanates

PEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 11 2005
John N Matthiessen
Abstract Four pure isothiocyanates (methyl, 2-propenyl, benzyl and 2-phenylethyl isothiocyanate), hydrolysing tissue of two brassicas rich in either 2-propenyl or 2-phenylethyl isothiocyanate, and the methyl isothiocyanate-generating pesticide metam-sodium were tested in vapour exposure tests for biological activity against a model soil insect both in vitro and in the presence of three contrasting soils and under four temperatures from 5 to 20 °C. The purpose was to develop an understanding of the factors controlling isothiocyanate release and maintenance in soil in order to identify advantageous attributes to seek in utilising brassicas for isothiocyanate-based biofumigation. Methyl isothiocyanate, structurally the simplest and the most volatile, was the most biologically active isothiocyanate under all conditions. It was less affected by the presence of soil and by lower temperature than the longer-chain aliphatic 2-propenyl isothiocyanate. The activity of the less volatile aromatic isothiocyanates was reduced much more by soil, with a decline up to many thousand-fold in the presence of soil with high organic matter content at lower temperature. Metam-sodium closely reflected the methyl isothiocyanate results. The results indicate that brassicas rich in aliphatic isothiocyanates are more likely to have the potential to exert stronger isothiocyanate-based biofumigation effects than those similarly rich in aromatic isothiocyanates. Copyright © 2005 Society of Chemical Industry [source]

Photodynamic therapy for the treatment of a giant superficial basal cell carcinoma

PHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 1 2009
Donato Calista
Summary A 74-year-old man was referred to our department for the treatment of a 15 × 15 cm superficial basal cell carcinoma (BCC) on his lumbar region. As surgical excision was considered too destructive, photodynamic therapy (PDT) was proposed. Methyl 5-aminolevulinate (MAL) cream was applied under occlusion for 3 h before illumination with a light-emitting diode lamp with an emission peak of 632 nm, a fluence rate of 83.3 mW/cm, and a light dose of 37 J/cm. A second MAL-PDT session was repeated 1 week later. The neoplastic area healed in 30 days. No recurrence has occurred after a 40-month follow-up period, but clinical observation continues. Although surgery still remains the treatment of choice for giant BCC, for which the local invasiveness and metastatic potential are well known, we offered our patient the option of PDT because we believed that classical surgery could hardly provide the same satisfactory outcome. As far as we know, this is the first case of giant BCC treated with PDT. [source]

Evaluating Pochonia chlamydosporia in a double-cropping system of lettuce and tomato in plastic houses infested with Meloidogyne javanica

PLANT PATHOLOGY, Issue 4 2003
S. Verdejo-Lucas
The effect of Pochonia chlamydosporia, a facultative fungal parasite of nematode eggs, alone or in combination with oxamyl was evaluated in a double-cropping system of lettuce and tomato in unheated plastic houses infested with Meloidogyne javanica at two sites for two consecutive growing seasons. An additional treatment of methyl bromide fumigation was included to compare crop yield in nematode-free vs. nematode-infested soil. Final population densities, reproductive rate, root gall rating, and egg production were determined after each crop. Pochonia chlamydosporia was isolated from nematode eggs up to nine months after application to soil. The fungus survived in the rhizosphere for the entire growing season at one site, but only at low densities. Final population densities of M. javanica decreased after cultivation of lettuce and increased after tomato, and this pattern of population fluctuation was unaffected by treatment, experiment or site. The reproductive rate on lettuce was equal to or below 1, and it was similar among treatments in both experiments at both sites. Eggs were not found on lettuce roots. On tomato, the reproductive rate in the fungus + oxamyl treatment was significantly lower (P < 0·05) than other treatments in experiment 1 at both sites. Fungus + oxamyl consistently reduced root gall ratings on tomato in all cases, but numbers of eggs per g root varied depending on treatment. Methyl bromide-treated plots remained free of M. javanica at the end of the 2-year study. [source]

NMDA potentiation by visible light in the presence of a fluorescent neurosteroid analogue

THE JOURNAL OF PHYSIOLOGY, Issue 12 2009
Lawrence N. Eisenman
N -Methyl- d -aspartate (NMDA) receptors are widely studied because of their importance in synaptic plasticity and excitotoxic cell death. Here we report a novel method of potentiating NMDA receptors with fluorescence excited by blue (480 nm) light. In the presence of 300 nm of a (7-nitro-2,1,3-benzoxadiazol-4-yl) amino (NBD)-tagged neuroactive steroid carrier C2-NBD-(3,,5,)-3-hydroxypregnan-20-one (C2-NBD 3,5,P), responses of cultured hippocampal neurons to 10 ,m NMDA were potentiated to 219.2 ± 9.2% of the baseline response (100%) by a 30 s exposure to 480 nm light. The potentiation decayed back to baseline with a time constant of 80.6 s. Responses to 1 ,m and 100 ,m NMDA were potentiated to 147.9 ± 9.6% and 174.1 ± 15.6% of baseline, respectively, suggesting that visible-light potentiation is relatively insensitive to NMDA concentration. Peak autaptic NMDA responses were potentiated to 178.9 ± 22.4% of baseline. Similar potentiation was seen with 10 ,m NBD-lysine, suggesting that visible-light potentiation is not a steroid effect. Potentiation was also seen with a steroid analogue in which the NBD was replaced with fluorescein, suggesting that NBD is not the only fluorophore capable of supporting visible-light potentiation. UV light and redox potentiation of NMDA receptors largely occluded subsequent blue light potentiation (127.7 ± 7.4% and 120.2 ± 6.2% of baseline, respectively). The NR1a(C744A,C798A) mutant that is insensitive to redox and UV potentiation was also largely unaffected by visible-light potentiation (135.0 ± 10.0% of baseline). Finally, we found that the singlet oxygen scavenger furfuryl alcohol decreased visible-light potentiation. Collectively, these data suggest that visible-light potentiation of NMDA receptors by fluorescence excitation shares mechanisms with UV and redox potentiation and may involve singlet oxygen production. [source]

Methyl ,- d -galactopyranosyl-(1,4)-,- d -allopyranoside tetrahydrate

ACTA CRYSTALLOGRAPHICA SECTION C, Issue 9 2010
Wenhui Zhang
The title compound, C13H24O11·4H2O, (I), crystallized from water, has an internal glycosidic linkage conformation having ,, (O5Gal,C1Gal,O1Gal,C4All) = ,96.40,(12)° and ,, (C1Gal,O1Gal,C4All,C5All) = ,160.93,(10)°, where ring-atom numbering conforms to the convention in which C1 denotes the anomeric C atom, C5 the ring atom bearing the exocyclic hydroxymethyl group, and C6 the exocyclic hydroxymethyl (CH2OH) C atom in the ,Galp and ,Allp residues. Internal linkage conformations in the crystal structures of the structurally related disaccharides methyl ,-lactoside [methyl ,- d -galactopyranosyl-(1,4)-,- d -glucopyranoside] methanol solvate [Stenutz, Shang & Serianni (1999). Acta Cryst. C55, 1719,1721], (II), and methyl ,-cellobioside [methyl ,- d -glucopyranosyl-(1,4)-,- d -glucopyranoside] methanol solvate [Ham & Williams (1970). Acta Cryst. B26, 1373,1383], (III), are characterized by ,, = ,88.4,(2)° and ,, = ,161.3,(2)°, and ,, = ,91.1° and ,, = ,160.7°, respectively. Inter-residue hydrogen bonding is observed between O3Glc and O5Gal/Glc in the crystal structures of (II) and (III), suggesting a role in determining their preferred linkage conformations. An analogous inter-residue hydrogen bond does not exist in (I) due to the axial orientation of O3All, yet its internal linkage conformation is very similar to those of (II) and (III). [source]

Methyl ,- d -fructopyranoside

ACTA CRYSTALLOGRAPHICA SECTION C, Issue 7 2010
Thorsten Allscher
In methyl ,- d -fructopyranoside, C7H14O6, the thermodynamically most stable methyl glycoside of the ketose d -fructose, the pyranose ring is close to being an ideal 2C5 chair. The compound forms bilayers involving a complex hydrogen-bonding pattern of five independent hydrogen bonds. Graph-set analysis was applied to distinguish the hydrogen-bond patterns at unary and higher level graph sets. [source]

6,-Methyl- B -norandrostenedione

ACTA CRYSTALLOGRAPHICA SECTION C, Issue 4 2010
L. C. R. Andrade
The title compound, C19H26O2, a B -norandrogen with a 6,-methyl group, is a recently identified and experimentally tested potent new aromatase inhibitor. It shares structural and physicochemical similarities both with the natural substrate of the enzyme, androstenedione, and with exemestane, another potent aromatase inhibitor having a 6-methylidene group. X-ray diffraction results indicate that the B -nor molecule and exemestane have nearly the same oxygen,oxygen and methyl,methyl separations, though they have distinct configurations of the hydrophobic groups at the 6-position. These structural comparisons allow correlations to be inferred between the active site geometry of the molecules and the aromatase inhibition power of the studied compound. [source]

Enantioselective, Thiourea-Catalyzed Intermolecular Addition of Indoles to Cyclic N -Acyl Iminium Ions,

ANGEWANDTE CHEMIE, Issue 34 2009
Emily
Freiwild für Indole sind N -Acyliminium-Ionen als Reaktionszwischenstufen, die unter der katalytischen Wirkung einer chiralen Thioharnstoff-Schiff-Base einer intermolekularen Addition dieser Nucleophile unterliegen. Die Methode wurde genutzt, um aus einfachen Vorstufen eine Vielfalt von funktionalisierten Indolgerüsten mit hoher Enantioselektivität aufzubauen (siehe Schema; TMS=Trimethylsilyl; R=H, Me, Vinyl, OMe, F, Cl, Br; R1=Benzyl, Methyl; n=1,2). [source]

Methyl

Selected Abstracts

MODULATORY EFFECT OF NARINGENIN ON N -METHYL- N, -NITRO- N -NITROSOGUANIDINE- AND SATURATED SODIUM CHLORIDE-INDUCED GASTRIC CARCINOGENESIS IN MALE WISTAR RATS