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Target Compounds (target + compound)
Selected AbstractsWastewater treatment plants as a pathway for aquatic contamination by pharmaceuticals in the Ebro river basin (Northeast Spain)ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2007Meritxell Gros Abstract The occurrence of 28 pharmaceuticals of major human consumption in Spain, including analgesics and anti-inflam-matories, lipid regulators, psychiatric drugs, antibiotics, antihistamines, and ,-blockers, was assessed along the Ebro river basin, one of the biggest irrigated lands in that country. Target compounds were simultaneously analyzed by off-line solid-phase extraction, followed by liquid chromatography-tandem mass spectrometry. The loads of detected pharmaceuticals and their removal rates were studied in seven wastewater treatment plants (WWTPs) located in the main cities along the basin. Total loads ranged from 2 to 5 and from 0.5 to 1.5 g/d/1,000 inhabitants in influent and effluent wastewaters, respectively. High removal rates (60,90%) were achieved mainly for analgesics and anti-inflammatories. The other groups showed lower rates, ranging from 20 to 60%, and in most cases, the antiepileptic carbamazepine, macrolide antibiotics, and trimethoprim were not eliminated at all. Finally, the contribution of WWTP effluents to the presence of pharmaceuticals in receiving river waters was surveyed. In receiving surface water, the most ubiquitous compounds were the analgesics and anti-inflammatories ibuprofen, diclofenac, and naproxen; the lipid regulators bezafibrate and gemfibrozil; the antibiotics erythromycin, azithromycin, sulfamethoxazole, trimethoprim, and less frequently, ofloxacin; the antiepileptic carbamazepine; the antihistamine ranitidine; and the ,-blockers atenolol and sotalol. Although levels found in WWTP effluents ranged from low ,g/L to high ng/L, pharmaceuticals in river waters occurred at levels at least one order of magnitude lower (low ng/L range) because of dilution effect. From the results obtained, it was proved that WWTP are hot spots of aquatic contamination concerning pharmaceuticals of human consumption. [source] Synthesis of Peptide-PNA-Peptide Conjugates by Semi-Solid-Phase Chemical Ligation Combined with Deactivation/Capture of Excess ReactantsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 4 2004Martijn C. de Koning Abstract An expeditious route to peptide-PNA-peptide conjugates following a two-step native chemical ligation (NCL) strategy is described. A cys-PNA-thioester is immobilized on PEGA-aldehyde resin by thiazolidine formation, followed by capping of excess resin aldehydes. The first NCL reaction is then performed with the immobilized PNA-thioester, to give, after release from the solid support, the cys-PNA-peptide intermediate with relatively high purity. The latter is then converted into the target compound by the second NCL reaction with a thioester peptide, the excess of which is captured using a cysteine-PEGA resin. The resulting peptide-PNA-peptide can then be readily isolated by a simple purification step. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004) [source] A Synthesis Detour to Planar-Diastereoisomeric Ferrocene Derivatives around an Unexpected Rearrangement of ortho -Lithiated Kagan's Template [S(S)] - (p -Tolylsulfinyl)ferroceneHELVETICA CHIMICA ACTA, Issue 4 2007Immo Weber Abstract Usually, ortho lithiation of Kagan's template 1 and quenching with electrophiles leads highly diastereoselectively to planar-chiral 1,2-disubstituted ferrocenes. Surprisingly, lithiation of 1 with lithium diisopropylamide (LDA) followed by addition of paraformaldehyde afforded regioisomer (+)-{[S(S)] - [4-(2-hydroxyethyl)phenyl]sulfinyl}ferrocene (2), which was converted to (+)-{[S(S)] - {4-{2-[(methylsulfonyl)oxy]ethyl}phenyl}sulfinyl}ferrocene (3) (Scheme,1). The desired diastereoisomer (l)-1-(hydroxymethyl)-2-(p -tolylsulfinyl)ferrocene (5) in turn could also be obtained by ortho lithiation of 1 with LDA but by quenching with DMF to yield aldehyde 4 first, which then was reduced with NaBH4 to 5. Finally, target compound (l)-1-[(dimethylamino)methyl]-2-(p -tolylsulfinyl)ferrocene (6) was obtained by substitution of the OH group of 5 under mild conditions or directly by ortho lithiation of 1 with lithio-2,4,6-triisopropylbenzene (=2,4,6-triisopropylphenyl)lithium; LTP) followed by quenching with N,N -dimethylmethyleneiminium chloride. At low temperatures, reaction of 1 with LDA leads, via the preferred diastereoisomeric transition state ,exo'- 7 and under extrusion of a (diisopropylamine)lithium complex of type 8, in a highly selective manner, to diastereoisomeric ortho -lithiated chelate (l)- 9 (Scheme,2). The reaction of 1 to 2 is explained by a rearrangement of (l)- 9 to {[S(S)],[4-(lithiomethyl)phenyl]sulfinyl}ferrocene 10, which is acid-catalyzed by coordinated diisopropylamine in complexes of type 8. This rearrangement is not observed if LTP is used as base or, in case LDA is applied, if the electrophile is sufficiently reactive at low temperatures. [source] Synthesis of a Potential 10E4 Tetrasaccharide Antigen Involved in Scrapie PathogenesisHELVETICA CHIMICA ACTA, Issue 11 2006Pascal Bindschädler Abstract To test the hypothesis that tetrasaccharide 3 is involved in scrapie pathogenesis, tetrasaccharide derivative 32 functionalized with an amine linker at the reducing end was synthesized. A (2,+,2) glycosylation approach was chosen to furnish the target compound in fully protected form. To investigate its biological role, tetrasaccharide 32 was further functionalized to the corresponding thiol 33 using Traut's reagent. During the course of the synthesis, the N,N -diacetyl protecting group proved surprisingly labile to radical and acidic conditions. [source] Integration of Solventless Reaction in a Multi-Step Process: Application to an Efficient Synthesis of PA-824ADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 13 2007Akihiro Orita Abstract In order to improve redundant synthetic processes, the integration of a solventless reaction has proved to be useful for gaining high reaction mass efficiency (RME) as well as reducing the amount of solvents. This concept was applied to synthesis of PA-824, a potential antituberculosis drug. Thus, the solventless ring-opening reaction of glycidyl silyl ether with dinitroimidazole was connected to succeeding solution reactions. The ring-opening of glycidol followed by selective silylation of the primary hydroxy group under solventless conditions was also feasible. As a consequence, the overall yield of the target compound was nearly tripled, and thus the RME values were increased more than 2.5 times while the amount of necessary solvents was decreased to less than 1/3. [source] Chemoenzymatic Route to Both Enantiomers of a 1-Isopropyl-3a-methyloctahydroinden-4-one Derivative: A Synthetic Intermediate for Sesqui- and DiterpenoidsADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 7-8 2005Shigeo Fujieda Abstract On the way to a chemoenzymatic synthesis of a key intermediate for sesquiterpenoids and diterpenoids, 2-methyl-2-(4-methyl-3-oxopentyl)-1,3-cyclohexanedione was reduced with the whole cells of yeast biocatalysts. Torulaspora delbrueckii NBRC10921 reduced a cyclic ketone of three carbonyl groups in an enantiofacially selective manner (re -face attack), but there was poor enantiotopic group selectivity between two carbonyl groups on the cyclohexane ring to yield a mixture of diastereomeric products. Candida floricola IAM13115 reduced mainly the pro -(R) carbonyl group. In contrast, the reduction proceeded in an enantiofacially poorly selective manner to give another set of diastereomeric products. In both cases, another carbonyl group on the side chain worked as a ,trapping arm' of the resulting secondary alcohol. The diastereomeric products were effectively separated as the ,syn' or ,cis' isomer exclusively exist in the intramolecular hemiacetal structure, while ,anti' or ,trans' isomer being an equilibrated mixture of cyclic hemiacetal and open-chain hydroxyketone (ca. 0.7,:,1). Starting separately from the enantiomerically enriched products as above, both enantiomers of the target compound, a key intermediate for terpenoids, were efficiently prepared via stereoselective ring closure under pinacol coupling reaction conditions. Furthermore, a daucane sesquiterpene intermediate, a hydroazulene derivative, was provided after one-carbon homologation of the six-membered ring. [source] Recovery of Aroma Compounds from Dilute Model Blueberry Solution by PervaporationJOURNAL OF FOOD SCIENCE, Issue 9 2003M. PENG ABSTRACT Pervaporation (PV) is a membrane-separation process showing unique capability of separating target compound(s) from dilute systems. Experiments were performed on a bench-scale flat sheet PV unit with a model solution to evaluate separation factor of 6 constituent aroma compounds (1-hexanol, 1-heptanol, trans-2-hexenal, ethyl acetate, linalool, and d-limonene), representing some of typical flavoring ingredients from blueberry juice. The results showed that separation factor was in the range of 70 to 430, depending on molecule size and polarity property of the compounds. Except for 1-heptanol, all compounds showed no significant coupling effect in the mixture system. The effect of temperature was also examined for a given feed-flow rate. Keywords: pervaporation, membrane, aroma compounds, blueberry, multicomponent diffusion [source] N1'-(p -[18F]Fluorobenzyl)naltrindole (p -[18F]BNTI) as a potential PET imaging agent for DOP receptorsJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 10 2006Eyup Akgün Abstract The N1'-(p -fluorobenzyl)naltrindole 5 has been synthesized by reaction of 3- O -benzyl NTI 3 with p -fluorobenzylbromide under phase transfer catalysis. The subsequent 3- O -benzyldeprotection of 4 in HBr/CH3COOH gave the target compound 5 in three steps from naltrindole 2. p -FBNTI 5 is a novel delta opioid receptor antagonist (Ki=0.00312 nM) and antagonizes the delta opioid (DOP) agonist, DPDPE, with a Ke=1.55 nM in the mouse vas deferens preparation. Using the same synthetic strategy the synthesis of p -[18F]BNTI 10 was undertaken. The final yield was 4% and the specific activity varied in a range of 250,400 mCi/µmol. Copyright © 2006 John Wiley & Sons, Ltd. [source] Utility of 1,3,4,6-tetra- O -acetyl-2-deoxy-2-[18F]fluoro-glucopyranoside for no-carrier-added 18F-glycosylation of amino acidsJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 10 2005Simone Maschauer Abstract A radiochemical method for the 18F-glycosylation of amino acid side chains was developed starting from peracetylated 2-deoxy-2-[18F]fluoroglucopyranoside (TA-[18F]FDG). O -(2-deoxy-2-[18F]fluoro- D -glucopyranosyl)- L -serine and the corresponding threonyl compound were obtained in a radiochemical yield of 25% and 12% (related to [18F]fluoride), respectively, after Zemplén deprotection within a total reaction time of 90 min. The anomeric configuration of the corresponding 19F-substituted compounds revealed preferential , -stereoselectivity. The 18F-glycosylation method using TA-[18F]FDG is compatible with the short half-life of fluorine-18 and combines glycosylation and 18F-labelling of a target compound within a single reaction step. TA-[18F]FDG is a promising 18F-labelled prosthetic group and could be adapted to 18F-labelling of bioactive peptides to study their pharmacokinetics using positron emission tomography (PET). Copyright © 2005 John Wiley & Sons, Ltd. [source] Determination of polycyclic aromatic hydrocarbons in olive oil by a completely automated headspace technique coupled to gas chromatography-mass spectrometryJOURNAL OF MASS SPECTROMETRY (INCORP BIOLOGICAL MASS SPECTROMETRY), Issue 6 2006Francisco J. Arrebola Abstract A new and completely automated method for the determination of ten relevant polycyclic aromatic hydrocarbons (PAHs) in olive oil is proposed using an extraction by the headspace (HS) technique. Quantification and confirmation steps are carried out by gas chromatography-mass spectrometry (GC-MS) combining simultaneously selected-ion monitoring (SIM) and tandem mass spectrometry (MS/MS). This combination offers on one hand an increased sensitivity and on the other hand, selective and reliable qualitative information. Sample pretreatment or clean-up are not necessary because the olive oil sample is put directly into an HS vial, automatically processed by HS and introduced into the GC-MS instrument for analysis. Because of its high selectivity and sensitivity, a triple-quadrupole (QqQ) detector coupled with the gas chromatograph allows us to limit handling. Each sample is completely processed in approximately 63 min (45 min for HS isolation and 18 min for GC-MS determination), a reduced time compared with previously published methods. The chemical and instrumental variables were preliminarily optimized using uncontaminated olive oil samples spiked with 25 µg kg,1 of each target compound. The final method was validated to ensure the quality of the results. The precision was satisfactory, with relative standard deviation (RSD) values in the range 3,9%. Recovery rates ranged from 96 to 99%. Limits of detection (LOD) were calculated as 0.02,0.06 µg kg,1 and the limits of quantification (LOQ) were obtained as 0.07,0.26 µg kg,1. It must be mentioned that the LOD and LOQ are much lower than the maximum levels established by the European Union (EU) in oils and fats intended for direct human consumption or for use as an ingredient in foods, which are set at 2 µg kg,1. All the figures of merit are completely in accordance with the latest EU legislation. This fact makes it possible to consider the proposed method as a useful tool for the control of PAHs in olive oils. Copyright © 2006 John Wiley & Sons, Ltd. [source] Preparation of a super-long two column chromatography system and its application in separating glycosylated puerarinBIOMEDICAL CHROMATOGRAPHY, Issue 12 2009Shouchuang Zhu Abstract Separation of Puerarin-7- O -glucoside from its precursor, puerarin, using a common chromatography column packed with AB-8 macroporous resin was unsuccessful. Therefore, in this study a 8,m super-long flexible reinforced PVC column was externally added to the common column in order to improve the chromatography efficiency by increasing the number of theoretical plates. Both the PVC and common columns were separately packed with AB-8 macroporous resin slurry. The packed PVC column was coiled after washing and stored until use. The microbial transformation mixture with puerarin-7- O -glucoside and puerarin (250,mL) was loaded onto the common column, followed by washing with 2000,mL H2O. After attaching the coiled external PVC column to the common column, a linear gradient of 10,30% ethanol was applied to elute the target compound. Two peaks appeared: peak I contained puerarin-7- O -glucoside at 97.9% purity and 88.1% recovery rate, and peak II was puerarin at 98.7% purity and 87.0% recovery rate. The use of the coiled external flexible reinforced PVC column avoided spatial restriction for long columns, which made it much more convenient for column packing and chromatography operations. Furthermore, this method eliminated the resin blockage problem caused by stationary water pressure in a rigid vertical long column. Using an external super-long column, the PVC tube was connected with the common column only during elution, which avoided delay in time period during sample loading and column washes associated with the use of long external columns. Copyright © 2009 John Wiley & Sons, Ltd. [source] Modeling with a view to target identification in metabolic engineering: A critical evaluation of the available toolsBIOTECHNOLOGY PROGRESS, Issue 2 2010Jo Maertens Abstract The state of the art tools for modeling metabolism, typically used in the domain of metabolic engineering, were reviewed. The tools considered are stoichiometric network analysis (elementary modes and extreme pathways), stoichiometric modeling (metabolic flux analysis, flux balance analysis, and carbon modeling), mechanistic and approximative modeling, cybernetic modeling, and multivariate statistics. In the context of metabolic engineering, one should be aware that the usefulness of these tools to optimize microbial metabolism for overproducing a target compound depends predominantly on the characteristic properties of that compound. Because of their shortcomings not all tools are suitable for every kind of optimization; issues like the dependence of the target compound's synthesis on severe (redox) constraints, the characteristics of its formation pathway, and the achievable/desired flux towards the target compound should play a role when choosing the optimization strategy. © 2010 American Institute of Chemical Engineers Biotechnol. Prog., 2010 [source] A Method for the Rapid Discovery of Naturally Occurring Products by Proteins Immobilized on Magnetic Beads and Reverse Affinity ChromatographyCHEMISTRY - AN ASIAN JOURNAL, Issue 12 2009Midori Abstract A highly efficient screening method for naturally occurring products that bind to a specific target protein was demonstrated by using hVDR magnetic beads. The native ligand 1,,25(OH)2 VD3 (1) was selectively bound by hVDR magnetic beads when present in a mixture of natural compounds. Furthermore, this method was shown to be applicable to the identification of natural products that interact with a specific protein immobilized on the beads from an extract of a natural resource. Two new natural compounds were isolated by this method. This approach will be helpful for the discovery of novel, naturally occurring products that bind to specific target proteins. This method has the further advantages that it can identify the HPLC peak corresponding to the target compound for isolation, as well as provide important UV, CD, or MS profile information. [source] Synthesis and HPLC enantioseparation of the cyclopropane analogue of valine (c3Val)CHIRALITY, Issue 1 2005Ana I. Jiménez Abstract A new and efficient method is presented for the preparation of the N -Boc-protected cyclopropane analogue of valine, 1-(N-tert -butoxycarbonyl)amino-2,2-dimethylcyclopropanecarboxylic acid, both in racemic and enantiomerically pure forms. Cyclopropanation of the exocyclic double bond of 2-phenyl-4-isopropylidene-5(4H)-oxazolone with diazomethane followed by elaboration of the heterocyclic moiety provided multigram quantities of the racemic target compound. Subsequent HPLC resolution of a racemic precursor on a noncommercial chiral stationary phase has given access to enantiomerically pure products. Almost 1.5 g of the first-eluted enantiomer and 1.0 g of the second-eluted enantiomer have been isolated in optically pure form using a 150 × 20 mm ID column containing mixed 10-undecenoate/3,5-dimethylphenylcarbamate of cellulose covalently bonded to allylsilica gel with a mixture of hexanes/tert -butyl methyl ether/ethyl acetate as the mobile phase. Chirality 17:22,29, 2005. ©2004 Wiley-Liss, Inc. [source] Screening for the calstabin-ryanodine receptor complex stabilizers JTV-519 and S-107 in doping control analysisDRUG TESTING AND ANALYSIS, Issue 1 2009Mario Thevis Abstract Recent studies outlined the influence of exercise on the stability of the skeletal muscle calstabin1-ryanodine receptor1-complex, which represents a major Ca2+ release channel. The progressive modification of the type-1 skeletal muscle ryanodine receptor (RyR1) combined with reduced levels of calstabin1 and phosphodiesterase PDE4D3 resulted in a Ca2+ leak that has been a suggested cause of muscle damage and impaired exercise capacity. The use of 1,4-benzothiazepine derivatives such as the drug candidates JTV-519 and S-107 enhanced rebinding of calstabin1 to RyR1 and resulted in significantly improved skeletal muscle function and exercise performance in rodents. Due to the fact that the mechanism of RyR1 remodelling under exercise conditions were proven to be similar in mice and humans, a comparable effect of JTV-519 and S-107 on trained athletes is expected, making the compounds relevant for doping controls. After synthesis of JTV-519, S-107, and a putative desmethylated metabolite of S-107, target compounds were characterized using nuclear magnetic resonance spectroscopy and electrospray ionization (ESI),high-resolution/high-accuracy Orbitrap mass spectrometry. Collision-induced dissociation pathways were suggested based on the determination of elemental compositions of product ions and H/D-exchange experiments. The most diagnostic product ion of JTV-519 was found at m/z 188 (representing the 4-benzyl-1-methyl piperidine residue), and S-107 as well as its desmethylated analog yielded characteristic fragments at m/z 153 and 138 (accounting for 1-methoxy-4-methylsulfanyl-benzene and 4-methoxy-benzenethiol residues, respectively). The analytes were implemented in existing doping control screening procedures based on liquid chromatography, multiple reaction monitoring and simultaneous precursor ion scanning modes using a triple quadrupole mass spectrometer. Validation items such as specificity, recovery (68,92%), lower limit of detection (0.1,0.2 ng/mL), intraday (5.2,18.5%) and interday (8.7,18.8%) precision as well as ion suppression/enhancement effects were determined. Copyright © 2009 John Wiley & Sons, Ltd. [source] A Straightforward Protocol for the Solution-Phase Parallel Synthesis of Ceramide AnaloguesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 1 2008Santiago Grijalvo Abstract A simple solution-phase protocol for the synthesis of ceramide analogues from easily accessible enantiopure scaffolds is disclosed. The method relies on the use of nucleophilic thiolates or phenoxides and appropriate supported reagents or scavengers to give the target compounds in good overall yields. The method is easily adaptable to combinatorial protocols and also amenable to automated processes for the generation of small-to-medium-sized libraries for further screening.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Synthesis of Tyrosine-Derived Tetrahydroisoquinolines by Lewis Acid Catalyzed Cyclization of N -(Phenylsulfonyl)alkyloxazolidinones,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 33 2007Stefan Tussetschläger Abstract N -Boc-protected tyrosine esters 5a,b were converted into tetrahydroisoquinolines 13 and 14 in four steps by reduction and ring closure to oxazolidinones 9 and 10, addition of benzenesulfinic acid and aldehydes to sulfones 11 and 12 and subsequent Lewis acid catalyzed cyclization. In the case of m -tyrosine derivative 5a, selective protection with bromine prevented the formation of undesired regioisomers. Debromination of target compounds 13 was readily achieved under radical reduction conditions by using Bu3SnH/AIBN. Tetrahydroisoquinolines 13 and 14 were isolated as single diastereomers whose trans configuration was confirmed by X-ray crystal structure analysis. Partial epimerization of trans - 13i and trans - 21 to the corresponding cis diastereomers was achieved under basic conditions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Design of Cyclopentaisoxazoline Amino Acids as Conformationally Constrained Agonists at Glutamate ReceptorsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 22 2003Paola Conti Abstract We have prepared four isomeric 3-hydroxycyclopentaisoxazoline amino acids 12,15, which represent analogues of glutamic acid having restricted conformations, through a strategy based on the 1,3-dipolar cycloaddition of bromonitrile oxide to a suitably protected 1-aminocyclopent-2-enecarboxylic acid. These target compounds proved to be inactive when assayed at ionotropic and metabotropic glutamate receptors, except for 12 which is an agonist primarily at mGluR5 (EC50 = 79 ,M), but is less active at mGluR2 and only marginally active at mGluR1. The biological data are accounted for through comparison of the conformational profiles of the test compounds with that of reference agonists, i.e., N -methyl- D -aspartate (NMDA, 2), and 1-aminocyclopentane-1,3-dicarboxylic acids [trans -ACPD, 10; cis -ACPD, 11]. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Quantitation of suspected allergens in fragrances (Part I): evaluation of comprehensive two-dimensional gas chromatography for quality controlFLAVOUR AND FRAGRANCE JOURNAL, Issue 2 2004Robert Shellie Abstract An evaluation of comprehensive two-dimensional (2D) gas chromatography (GC×GC) was performed to assess its suitability for the analysis of volatile fragrance components, recognized by the European Commission's Scienti,c Committee on Cosmetics and other Non-food Products (SCCNFP) as possible skin sensitizers. The 24 volatile components listed by the SCCNFP were baseline-resolved or better within one 30 min analysis. High-quality calibration data for standard mixtures were obtained, with R2 > 0.998 over the concentration range 2,1000 mg/l. However, the analysis of small spiked amounts of target compounds in truly complex fragrances was problematic, due to uncertainty in component assignment. The bene,ts and limitations of GC×GC are reported, and a discussion of the proposed directions for the solution of this analysis is provided. Copyright © 2004 John Wiley & Sons, Ltd. [source] Facile Synthesis of Diastereoisomerically and Optically Pure 2-Substituted Hexahydro-1H -pyrrolizin-3-onesHELVETICA CHIMICA ACTA, Issue 8 2005Romain Siegrist We report a short synthetic route that provides optically active 2-substituted hexahydro-1H -pyrrolizin-3-ones in four steps from commercially available Boc (tert -but(oxy)carbonyl))-protected proline. Diastereoisomers (,)- 11 and (,)- 12 were assembled from the proline-derived aldehyde (,)- 8 and ylide 9via a Wittig reaction and subsequent catalytic hydrogenation (Scheme,3). Cleavage of the Boc protecting group under acidic conditions, followed by intramolecular cyclization, afforded the desired hexahydro-1H -pyrrolizinones (,)- 1 and (+)- 13. Applying the same protocol to ylide 19 afforded hexahydro-1H -pyrrolizinones (,)- 25 and (,)- 26 (Scheme,5). The absolute configuration of the target compounds was determined by a combination of NMR studies (Figs.,1 and 2) and X-ray crystallographic analysis (Fig.,3). [source] Synthesis of N-Heteroaryl(trifluoromethyl)hydroxyalkanoic Acid Esters by Highly Efficient Solid Acid-Catalyzed Hydroxyalkylation of Indoles and Pyrroles with Activated Trifluoromethyl KetonesADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 14 2005Mohammed Abid Abstract The synthesis of N-heteroaryl(trifluoromethyl)hydroxyalkanoic acid esters by solid acid-catalyzed Friedel,Crafts hydroxyalkylation of indoles and pyrroles with ethyl 3,3,3-trifluoropyruvate and ethyl 4,4,4-trifluoroacetoacetate is described. The inexpensive and readily available K-10 montmorillonite is found to be an efficient catalyst for the synthesis of a wide variety of trifluoromethylated indol-3-yl- and pyrrol-2-yl-hydroxypropionic and -butanoic acid esters. Using a series of substituted indoles and pyrroles the corresponding products were isolated in excellent yield (up to 98%) and 100% selectivity under mild experimental conditions, during very short reaction times. Beyond these, the ease of product isolation, catalyst stability and handling make this process an attractive, environmentally benign alternative for the synthesis of the target compounds. [source] Development of a Quantitative LC-MS/MS Method for the Analysis of Common Propellant Powder Stabilizers in Gunshot Residue,JOURNAL OF FORENSIC SCIENCES, Issue 4 2007Désiré Laza Ph.D. Abstract:, In traditional scanning electron microscopy/energy dispersive X-ray analysis of gunshot residue (GSR), one has to cope more and more frequently with limitations of this technique due to the use of lead-free ammunition or ammunition lacking heavy metals. New methods for the analysis of the organic components of common propellant powder stabilizers were developed based on liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). A multiple reactions monitoring scanning method was created for the screening of akardite II, ethylcentralite, diphenylamine, methylcentralite, N-nitrosodiphenylamine, 2-nitrodiphenylamine, and 4-nitrodiphenylamine, present in standards mixtures. Five out of seven of these target compounds can be selectively identified and distinguished from the two others with a high accuracy. Samples from the hands of a shooter were collected by swabbing and underwent solid phase extraction prior to analysis. Detection limits ranging from 5 to 115 ,g injected were achieved. Results from several firing trials show that the LC-MS/MS method is suitable for the detection of stabilizers in samples collected following the firing of 9 mm Para ammunitions. [source] Stereoselective synthesis and biological activities of diethyl (E)-{[4-cyano-5-[[(disubstitutedamino)methylene]amino]-3-(methylthio)- 1H -pyrazol-1-yl]substituited phenylmethyl}phosphonatesJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 3 2009Lin-Xia Xiao Diethyl {[5-amino-4-cyano-3-(methylthio)-1H -pyrazol-1-yl]substitutedphenylmethyl}phosphonates 3 were efficiently synthesized via the condensation of [(1-hydrazino)substitutedphenylmethyl]phosphonates 1 with 2-[bis(methylthio)methylene]malononitrile 2. 3 reacted with triethyl orthoformate to afford diethyl (E)-{[4-cyano-5-[(ethoxymethylene)amino]-3-(methylthio)-1H -pyrazol-1-yl]substitutedphenylmethyl}phosphonates 4, which reacted with various secondary amines at room temperature to provide the target compounds 5 in good yields. Their structures were confirmed by ir, 1H and 31P NMR, mass spectroscopy, and elemental analyses. The results of preliminary bioassay indicated that compounds 5 possess potent herbicidal activity against the roots of dicotyledonous (oil rape) plants at the dosage of 100 mg/L, and compounds 5c and 5g exhibit 80.8% and 76.7% inhibitory activity against Colletotrichum gossypi at the concentration of 50 mg/L, respectively. Abstract end data: J. Heterocyclic Chem., 46, 555 (2009). [source] Synthesis and biological activity of 3-[(6-chloropyridin-3-yl)methyl]-6-substituted-6,7-dihydro-3H -1,2,3-triazolo[4,5- d]-pyrimidin-7-iminesJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 5 2008Xiao-Bao Chen A series of 3-[(6-chloropyridin-3-yl)methyl]-6-substituted-6,7-dihydro-3H -1,2,3-triazolo[4,5- d]pyrimidin-7-imines were designed and synthesized via a multi-step sequence using 2-chloro-5-(chloromethyl)-pyridine as the starting material. Various primary aliphatic amines, hydrazine and hydrazide reacted with 3 to obtain the cyclization products 4. Their structures were confirmed by 1H NMR and elemental analyses, some of them were also confirmed by IR, 13C NMR, MS and single crystal X-ray diffraction. The preliminary bioassay indicated that some of the target compounds 4 displayed moderate to weak fungicidal activity and insecticidal activity. [source] Synthesis and biological activities of novel 1,3-bis[substituted-pyridyl (thiazolyl)methyl]-2-substitutedmethylideneimidazolidinesJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 4 2008Man Yan A series of novel 1,3-dissubstitutedpyridyl(thiazolyl)methyl-2-substituted-methylideneimidazolidine derivatives 2 and 4 were designed and synthesized via the N -alkylation of the disubstituted heterocyclic ketene aminal derivative 1. When 1 (R = CN, R' = COOC2H5) was used as the starting materials, mono N -alkylated reaction can take place in good yields owing to the presence of the intramolecular hydrogen bond. However, as for 1 (R = R' = CN), it is difficult to obtain pure mono N -alkylated product. The structures of the target compounds were confirmed by IR, 1H NMR, EI-MS and elemental analyses, and, in the case of 2c, by single crystal X-ray diffraction. The preliminary bioassay indicated that some of the title compounds possess moderate fungicidal and insecticidal activity. [source] Alkylation of azoles: Synthesis of new heterocyclic-based AT1 -non-peptide angiotensin (II) receptor antagonistsJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 3 2007Amal Al-Azmi Several novel analogues of Losartan 2 were synthesized as potential non-peptide angiotensin (II) receptor antagonists. In these non-peptide analogues, the tetrazole and the substituted imidazole rings of Losartan 2 were replaced, respectively, by a carboxylic acid function or its methyl ester and substituted triazole, imidazole or benzimidazole moieties. The biphenyl bromide precursor 3 (BPE) used to introduce the linker between the acid/ester function and the heterocyclic moiety was synthesized using Suzuki biphenyl coupling and then incorporated into the target molecule by simple nucleophilic substitution. The fixed N-aryl isomeric forms of several azole and benzimidazole tautomers were successfully separated by HPLC using 50% aqueous acetonitrile as eluent. Intermediate reaction products and final target compounds were fully characterized spectroscopically. [source] Synthesis of trisubstituted thiophenes designed as progesterone receptor modulatorJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 5 2006Weiqin Jiang When a known 2-[4-morpholino]-3-aryl-5-substituted thiophene, which showed moderate activity as a progesterone antagonist, was superimposed with a potent steroidal progesterone antagonist Org-33628, it showed a fair alignment in most parts of the molecules. According to the molecular modelling, displacement of the morpholine oxygen atom in the thiophene derivative with a carbonyl group would provide a better alignment with the C-3 carbonyl in Org-33628. Thus, a series of novel trisubstituted thiophenes bearing a cyclic ketone moiety was synthesized. Although these compounds only showed weak activities as progesterone receptor antagonists, all target compounds are novel and are fully characterized. [source] Heterocyclic compounds from 4h -3,1-benzoxazin-4-one derivatives as anticancer agentJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 7 2005Taha M Abdel-Rahman Behaviour of 2-(4-oxo-4H -benzo[d][l,3]oxazin-2-yl)-benzoic acid (1) towards nitrogen nucleophiles namely, hydrazine hydrate, in different solvents, ammonium acetate, and o -phenylenediamine has been investigated to give aminoquinazolin-4-one, benzotriazepinone, spiro-type compound, and nitrogen bridgehead compounds 3-5, respectively. Also, reactivity of the aminoquinazolin-4-one 2 towards carbon elec-trophiles such as ethyl acetoacetate, ethyl phenylacetate, ethyl chloroacetate, and aromatic aldehydes has been discussed. Reaction of Schiff s base 8 with sulfur nucleophiles namely o -aminothiophenol and/or thio-glycolic acid afforded Michael type adducts. Structural assignments, of products 1-24 have been confirmed by elemental analysis and spectral data (1H- and 13C -NMR and MS fragmentation). The bioassay indicates that some of the target compounds obtained have good selective anticancer activity. [source] Synthesis of thiophene/phenylene co-oligomers.JOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 5 2003We report the synthesis of various thiophene/phenylene co-oligomers with a total number of thiophene and benzene (phenylene) rings of 6 to 8. These compounds include a phenyl-capped sexithiophene, a thienyl-capped quaterphenylene, as well as block and alternating co-oligomers. The synthesis is based on either the Suzuki coupling reaction or the direct dimerization coupling. The latter method produces symmetric molecules with an even total ring number. These reaction schemes enabled us to obtain the target compounds in high quality. Although the resulting materials are difficult to dissolve in organic solvents and therefore difficult to identify by usual 1H nmr spectroscopy, they have successfully been identified through Fourier-transform ir spectroscopy. The specific group frequencies of ring-stretching and out-of-plane deformation modes are characteristic of the substitution pattern of the individual thiophene and benzene rings. [source] Synthesis of thiophene/phenylene co-oligomers.JOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 1 2000We report the synthesis of phenyl-capped oligothiophenes via improved synthetic schemes. These schemes are based on the Grignard coupling reaction and enable us to obtain the target compounds at high yields. The resulting materials have been fully characterized through nmr and ir spectroscopies. The ir analysis is particularly useful in characterizing the materials of higher molecular weight, since those materials are difficult to dissolve in organic solvent. We also show an improvement on preparation of halogenated (oligo)thiophenes that are used as intermediates for synthesizing the target compounds. An alternative synthetic route to the phenyl-capped oligothiophenes that utilizes the Suzuki coupling reaction is presented as well. [source] | ||||||||||||||||||||||||||||||||||