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Enantiomers
Kinds of Enantiomers Terms modified by Enantiomers Selected AbstractsPharmacokinetics of Levetiracetam and Its Enantiomer (R)-,-ethyl-2-oxo-pyrrolidine acetamide in DogsEPILEPSIA, Issue 7 2001Nina Isoherranen Summary: ,Purpose: The new antiepileptic drug, levetiracetam (LEV, ucb LO59), is a chiral molecule with one asymmetric carbon atom whose anticonvulsant activity is highly enantioselective. The purpose of this study was to evaluate and compare the pharmacokinetics (PK) of LEV [(S)-,-ethyl-2-oxo-pyrrolidine acetamide] and its enantiomer (R)-,-ethyl-2-oxo-pyrrolidine acetamide (REV) after i.v. administration to dogs. This is the first time that the pharmacokinetics of both enantiomers has been evaluated. Methods: Optically pure LEV and REV were synthesized, and 20 mg/kg of individual enantiomers was administered intravenously to six dogs. Plasma and urine samples were collected until 24 h, and the concentrations of LEV and REV were determined by an enantioselective assay. The levels of 2-pyrrolidone- N -butyric acid, an acid metabolite of LEV and REV, were determined by high-performance liquid chromatography (HPLC). The data were used for PK analysis of LEV and REV. Results: LEV and REV had similar mean ± SD values for clearance; 1.5 ± 0.3 ml/min/kg and volume of distribution; 0.5 ± 0.1 L/kg. The half-life (t1/2) and mean residence time (MRT) of REV (t1/2, 4.3 ± 0.8 h, and MRT, 6.0 ± 1.1 h) were, however, significantly longer than those of LEV (t1/2, 3.6 ± 0.8 h, and MRT, 5.0 ± 1.2 h). The renal clearance and fraction excreted unchanged for LEV and REV were significantly different. Conclusions: In addition to the enantioselective pharmacodynamics, ,-ethyl-2-oxo-pyrrolidine acetamide has enantioselective PK. The enantioselectivity was observed in renal clearance. Because REV has more favorable PK in dogs than LEV, the higher antiepileptic potency of LEV is more likely due to intrinsic pharmacodynamic activity rather than to enantioselective PK. [source] Sulfoxide-Directed Stereocontrolled Access to 2H -Chromans: Total Synthesis of the (S,R,R,R)-Enantiomer of the Antihypertensive Drug NebivololEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 12 2008M. Carmen Carreño Abstract A homochiral sulfoxide-directed reductive deoxygenation of 2-(p -tolylsulfinyl)methyl-2-chromanols allows the stereoselective formation of 2H -chromans with up to 95:5 diastereoisomeric ratio. This new methodology was appliedin a short and convergent enantioselective synthesis ofthe (S,R,R,R)-enantiomer of the antihypertensive drugNebivolol.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] A Temporary Stereocentre Approach for the Stereodivergent Synthesis of Either Enantiomer of ,-MethyloctanalEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 33 2007D. Gangani Niyadurupola Abstract The aldol reaction of a chiral N -(acyl)oxazolidin-2-one with 2-methyleneoctanal or (E)-2-methyloct-2-enal affords chiral aldol products whose alkene functionalities were hydrogenated using Brown's or Wilkinson's catalyst to afford syn - or anti -selective products with excellent levels of diastereocontrol. Subsequent retro -aldol cleavage of these syn - or anti -adducts resulted in the formation of either (R)- or (S)-enantiomer of ,-methyloctanal with no racemisation occurring, which could be derivatised in-situ to afford chiral dithiane, alcohol or ,,,-unsaturated ester products in enantiopure form.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Efficient Synthesis of Either Enantiomer of Ethyl 5-Hydroxyhept-6-enoateADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 8-9 2007Thomas Fischer Abstract The application of alcohol dehydrogenases as a key-step for the synthesis of the title compound is reported. 5-Hydroxyhept-6-enoates are versatile intermediates, e.g., for the synthesis of a variety of arachidonic acid metabolites. [source] Exclusive Observation of the (132R)-Enantiomer of Chlorophyll- c from a Diatom Chaetoseros calcitransPHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 2 2010Tadashi Mizoguchi Chiral high-performance liquid-chromatography (HPLC) for quantitative analysis of optically active chlorophyll(Chl)- c molecules, which are seen in many marine photosynthetic organisms, was developed. Chls- c have a single asymmetric carbon at the 132 -position, so their stereoisomers are (132R)- and (132S)-enantiomers. After the separation of each enantiomer, the stereochemistry was unambiguously characterized using its circular dichroism spectrum in comparison with that of the structure-related compound, protochlorophyllide- a. Moreover, Chls- c were carefully extracted from the cells of a diatom Chaetoseros calcitrans without racemization and were subjected to the chiral HPLC. The results clearly demonstrated that naturally occurring Chl- c molecules are enantiomerically pure (132R)-forms, which are generally found in photosynthetically active chlorophyllous pigments. [source] Stereocontrolled Synthesis of the C21,C38 Fragment of the Unnatural Enantiomer of the Antibiotic Nystatin A1CHEMISTRY - A EUROPEAN JOURNAL, Issue 6 2004Thilo Berkenbusch Dr. Abstract The C21,C38 fragment all- trans - 41 of the unnatural enantiomer 1 of nystatin A1 was prepared starting from the N -propionyl oxazolidinone 9. Aldol adduct ent - 8 (ee > 96,%) derived in two steps was hydroborated with (thexyl)BH2. Oxidative work-up and treatment with acid furnished ,-lactone 4. It contains the complete stereotetrade of the target molecule. The ,,,-unsaturated ester 28 was reached after another four steps. It should be a precursor for the polyene moieties of a variety of polyol,polyene macrolides. Illustrating that, the ,,,-unsaturated aldehyde 29 obtained from 28 and DIBAL was extended by 10 C atoms in four steps yielding the C21,C38 segment 41. The latter set of transformations included the regio- and stereoselective Claisen rearrangement 32,35. [source] Determination of the binding constants of modafinil enantiomers with sulfated ,-cyclodextrin chiral selector by capillary electrophoresis using three different linear plotting methodsELECTROPHORESIS, Issue 17 2010Khaldun M. Al Azzam Abstract Binding constants for the enantiomers of modafinil with the negatively charged chiral selector sulfated-,-CD (S-,-CD) using CE technique is presented. The calculations of the binding constants employing three different linearization plots (double reciprocal, X -reciprocal and Y -reciprocal) were performed from the electrophoretic mobility values of modafinil enantiomers at different concentrations of S-,-CD in the BGE. The highest inclusion affinity of the modafinil enantiomers were observed for the S -enantiomer,S-,-CD complex, in agreement with the computational calculations performed previously. Binding constants for each enantiomer,S-,-CD complex at different temperatures, as well as thermodynamic parameters for binding, were calculated. Host,guest binding constants using the double reciprocal fit showed better linearity (r2>0.99) at all temperatures studied (15,30°C) and compared with the other two fit methods. The linear van't Hoff (15,30°C) plot obtained indicated that the thermodynamic parameters of complexation were temperature dependent for the enantiomers. [source] Heart-cutting 2D-CE with on-line preconcentration for the chiral analysis of native amino acidsELECTROPHORESIS, Issue 6 2010Suzanne Anouti Abstract The use of transient moving chemical reaction boundary (tMCRB) was investigated for the on-line preconcentration of native amino acids in heart-cutting 2D-CE with multiple detection points using contactless conductivity detection. The tMCRB focusing was obtained by using ammonium formate (pH 8.56) as sample matrix and acetic acid (pH 2.3) as a BGE in the first dimension of the heart-cutting 2D-CE. Different experimental parameters such as the injected volume and the concentration in ammonium formate were optimized for improving the sensitivity of detection. A stacked fraction from the first dimension was selected, isolated in the capillary, and then separated in the second dimension in the presence of a chiral selector ((+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid). This on-line tMCRB preconcentration coupled with heart-cutting 2D-CE was applied with success to the chiral separation of D,L -phenylalanine, and D,L -threonine in a mixture of 22 native amino acids. The sample mixture was diluted in 0.8,M of ammonium formate, and injected at a concentration of 2.5,,M for each enantiomer with a volume corresponding to 10% of the total capillary volume. An LOD (S/N=3) of 2,,M was determined for L -threonine. [source] Effect of urea on analyte complexation by 2,6-dimethyl-,-CD in peptide enantioseparations by CEELECTROPHORESIS, Issue 21 2009Manuela Hammitzsch-Wiedemann Abstract The aim of the present study was the investigation of the effect of urea on analyte complexation in CD-mediated separations of peptide enantiomers by CE in the pH range of about 2,5. pH-independent complexation and mobility parameters in the absence and presence of 2,M urea were obtained by three-dimensional, non-linear curve fitting of the effective analyte mobility as a function of pH and heptakis-(2,6-di- O -methyl)-,-CD concentration. Urea led to decreased binding strength of the CD towards the protonated and neutral analyte enantiomers as well as to decreased mobilities of the free analytes. In contrast, mobilities of the fully protonated enantiomer,CD complexes as well as the pKa values of the free and complexed analytes increased. The effect of urea on separation efficiency varied with pH and CD concentration. In the case of Ala-Tyr and Ala-Phe, separations improved in the presence of urea at pH 2.2. In contrast, separations were impaired by urea at pH 3.8 and low concentrations of the CD. Decreased separation efficiency was noted for Asp-PheOMe and Glu-PheNH2 at low CD concentrations when urea was added but separations improved at higher CD concentrations over the entire pH range studied. The effect of urea on analyte complexation appeared to be primarily non-stereoselective. Furthermore, the pH-dependent reversal of the enantiomer migration order observed for Ala-Tyr and Ala-Phe can be rationalized by the complexation and mobility parameters. [source] Enantioselective determination of thyroxine enantiomers by ligand-exchange CE with UV absorbance and ICP-MS detectionELECTROPHORESIS, Issue 10 2009Jianzhen Kang Abstract A simple CE method has been developed for the separation and determination of thyroxine (T4) enantiomers in pharmaceutical formulations. The method was based on ligand-exchange mechanism using a Cu(II)/L -proline complex as chiral selector. The effects of different parameters affecting separation such as chiral selector concentration, organic additive, buffer pH and temperature were investigated. A baseline separation of the two enantiomers was obtained at a Cu(II)/L -proline ratio of 1:8 in a borate buffer (15,mmol/L, pH 9.6) containing 10%,v/v acetonitrile. Under the optimized conditions, precision linearity range and detection limits of the developed enantioselective CE method were evaluated and compared using two different detection systems: conventional UV detection at 226,nm and iodine (127I)specific detection ("chiral speciation") with ICP-MS. Both methodologies show adequate analytical performance characteristics with detection limits around 0.30,,g/mL for each enantiomer of T4. Finally, a levothroid pharmaceutical formulation sample was successfully analyzed using both developed methods CE-UV and CE-ICP-MS. [source] Chiral separation of the plant lignan matairesinol by capillary electrophoresis,ELECTROPHORESIS, Issue 17 2008Ulrike Müller Abstract Lignans are dimeric phenylpropanoid compounds in plants that enjoy increasing medicinal interest because of their phytoestrogen activity. Lignans are chiral compounds and for most natural occurring lignans, chirality is not known. Separation of racemic matairesinol by CE in a non-coated silica capillary with carboxymethyl-,-cyclodextrin as chiral selector in phosphate buffer was successful. Electrolyte and selector concentrations and pH were systematically optimized in order to obtain baseline separation and short analysis times. Matairesinol from safflower fruit was determined as (,)-enantiomer. Quantitation results for matairesinol with the optimized method after calibration with authentic lignan were very similar to those by HPLC. The limit of detection is 2,,g/mL sample by DAD detection. [source] Enantioselectivity of basic analytes in CZE enantioseparation under reversed-polarity mode using sulfated ,-cyclodextrins as chiral selectors: An unusual temperature effectELECTROPHORESIS, Issue 21 2006Chen-Hsing Lin Abstract Temperature effects on the enantioselectivity of basic analytes in CZE enantioseparation were studied under reversed-polarity mode using randomly sulfate-substituted ,-CDs (MI-S-,-CD) as chiral seletors. Two catecholamines (epinephrine and isoproterenol) and two structurally related compounds (octopamine and norephedrine) were selected as test compounds in an electrophoretic system at low pH. The mobility differences between the (+)-enantiomers and the (,)-enantiomers of the two catecholamines and dopamine at 40°C are greater than those at 25°C with MI-S-,-CD, even at a concentration as low as 0.3%,w/v. Thus the enantioselectivity of these three basic analytes increases with increasing temperature. This phenomenon results from the inequality of the temperature effect on the mobility of the two enantiomers. In contrast, norephedrine behaves differently. The (+)-enantiomers of these basic analytes were found to migrate faster than the (,)-enantiomers. Consequently, the unusual temperature effect on the enantioselectivity can be observed when the mobility difference of the (+)-enantiomer between 40 and 25°C is greater than that of the (,)-enantiomer using MI-S-,-CD at a concentration greater than about 0.7%,w/v for enantioseparation of isoproterenol, 0.4%,w/v for epinephrine, and 0.3%,w/v for octopamine. This unusual temperature effect offers the advantages to enhance enantioselectivity, to improve enantioseparation, and to reduce migration times. [source] (S)-Ibuprofen-imprinted polymers incorporating ,-methacryloxypropyl-trimethoxysilane for CEC separation of ibuprofen enantiomersELECTROPHORESIS, Issue 21 2006Qi-Liang Deng Abstract In this report, a novel preparation method of molecularly imprinted polymers (MIPs) for CEC was developed. Molecularly imprinted monolithic columns for (S)-ibuprofen were prepared and evaluated, in which charged entities responsible for establishing EOF have been derived from ,-methacryloxypropyltrimethoxysilane (,-MAPS), which was hydrolyzed following copolymerization with 4-vinylpyridine (4-VPY) and ethylene glycol dimethacrylate,(EDMA). The EOF and molecular recognition of the stationary phase were investigated in aqueous and nonaqueous media, respectively. The experimental results indicated that the material showed a reasonably stable EOF and the prepared separation materials were capable of separating racemic ibuprofen, a task that could not be accomplished by MIPs prepared in parallel, using methacrylic acid (MAA) as a functional monomer. The efficiency at pH,3.2 for the first-eluted enantiomer and the last-eluted enantiomer (the imprinted analyte) were 128,700 and 2100,plates/m, respectively. [source] Chiral separation of N -imidazole derivatives, aromatase inhibitors, by cyclodextrin-capillary zone electrophoresis.ELECTROPHORESIS, Issue 16 2004Mechanism of enantioselective recognition Abstract Baseline separation of ten new, substituted [1-(imidazo-1-yl)-1-phenylmethyl)] benzothiazolinone and benzoxazolinone derivatives with one chiral center was achieved using cyclodextrin-capillary zone electrophoresis (CD-CZE). A method for the enantiomeric resolution of these compounds was developed using neutral CDs (native ,-, ,-, ,-CDs or ,-, ,-, ,-hydroxypropyl (HP)-CDs) as chiral selectors. Operational parameters including the nature and concentration of the chiral selectors, pH, ionic strength, organic modifiers, temperature, and applied voltage were investigated. The use of neutral CDs provides enantiomeric resolution by inclusion of compounds in the CD cavity. The HP-,-CD and HP-,-CD were found to be the most effective complexing agents and allowed efficient enantiomeric resolutions. Optimal separation of N -imidazole derivatives was obtained using 50 mM phosphate buffer at pH 2.5 containing either HP-,-CD or HP-,-CD (7.5,12.5 mM) at 25°C, with an applied field of 0.50 kV·cm,1 giving resolution factors Rs superior to 1.70 with migration times of the second enantiomer less than 13 min. The same enantiomer migration order observed for all molecules can be related to a close interaction mechanism with CDs. The influence of structural features of the solutes on Rs and tm was studied. The lipophilic character (log kw) of the solutes and the apparent and averaged association constants of inclusion complexes for four compounds with the six different CDs led us to rationalize the enantioseparation mechanisms. The conclusions were corroborated with reversed-phase high-performance liquid chromatography (HPLC) on chiral stationary phases (CSPs) based on CDs. [source] Determination of enantiomeric purity of a novel COX-2 anti-inflammatory drug by capillary electrophoresis using single and dual cyclodextrin systemsELECTROPHORESIS, Issue 9 2003Carlos Pérez-Maseda Abstract E-6087 is the most advanced compound among the cyclooxygenase-2 (COX-2) inhibitor drugs developed in our company. Its activity is mainly associated with the S(,)-enantiomer (E-6232), whereas the R(,)-enantiomer (E-6231) becomes an impurity whose content should be determined. Five main impurities and degradation products of E-6232 have been found (E-6144, E-6024, E-6072, E-6397 and E-6132), and some of them co-elute with the distomer when using a chiral high-performance liquid chromatography (HPLC) method. Consequently, we have optimized the separation of all the impurities from the two enantiomers of E-6087 by capillary electrophoresis (CE), in order to use the method for the enantiomeric purity determination of E-6232. The effect of the methanol (MeOH) content in the background electrolyte (BGE), the sulfobutyl ether-,-cyclodextrin (SBE-,-CD) and heptakis-(2,6-di- O -methyl)-,-cyclodextrin (DM-,-CD) concentration, and the capillary temperature have been studied. Separation of all compounds could be achieved in different systems, either in a single CD-system (with SBE-,-CD) or in a dual CD-system (with DM-,-CD as a neutral CD). By using the dual CD system a limit of detection (LOD) and a limit of quantitation (LOQ) of 0.03% and 0.1% of distomer, respectively, were achieved*. [source] Electroenzymatic Synthesis of Chiral SulfoxidesENGINEERING IN LIFE SCIENCES (ELECTRONIC), Issue 2 2006C. Kohlmann Abstract Chloroperoxidase (CPO) from Caldariomyces fumago (E.C.,1.11.1.10) is able to enantioselectively oxidize various sulfides to the corresponding (R)-enantiomer of the sulfoxides. For these oxidations the enzyme requires an oxidant. Most commonly, tert -butyl hydroperoxide (TBHP) and hydrogen peroxide are used. As it is known that these oxidants inactivate the enzyme, the enzymatic reaction was combined with the electrochemical in situ generation of hydrogen peroxide. As substrates for this combination of an enzymatic and an electrochemical reaction methyl p-tolyl sulfide, 1-methoxy-4-(methylthio)benzene and N-MOC- L -methionine methyl ester were used to carry out batch experiments. [source] Dual enantioselective effect of the insecticide bifenthrin on locomotor behavior and development in embryonic,larval zebrafishENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2010Meiqing Jin Abstract Bifenthrin (BF) is a synthetic pyrethroid that targets the nervous system of insects and may have adverse effects on the behavior and development of nontarget organisms. However, no reports have been issued on the effects of different enantiomers on locomotor behavior for synthetic pyrethroids (SPs) in zebrafish, and whether locomotor activity is associated with the developmental toxicities remains unclear. In this study, enantioselectivity of BF (1S and 1R) on the acute locomotor activity and developmental toxicities of embryonic,larval zebrafish were first evaluated. The results indicated that 1R -BF was more toxic, causing morphological impairments, with a 96-h median effective concentration (EC50) of 226,µg/L for pericardial edema and 145,µg/L for curved body axis. Administration of 20,µg/L of one enantiomer of BF had differential effects on the locomotor activity of zebrafish larvae at 4 d postfertilization (dpf) under alternating light and dark conditions. Larvae treated with 1R -BF were not sensitive to the alteration of light to dark, and the locomotor activities were reduced to a level similar to that observed in light, which otherwise increased rapidly and markedly. However, 1S -BF did not alter the general pattern of zebrafish response to the light or dark compared with the control. The results demonstrated that the differential effects on development might have contributed to the enantioselectivity in the locomotor activity. The consistency of enantioselectivity with insecticidal activity may also indicate a common mode of action. Furthermore, 1R -BF accelerated the spontaneous movement and hatching process, whereas 1S -BF seemed to be inhibitory. The results suggest the need to link behavioral changes to developmental toxicities in order to achieve more comprehensive health risk assessments of chiral pesticides. Environ. Toxicol. Chem. 2010;29:1561,1567. © 2010 SETAC [source] Separation and aquatic toxicity of enantiomers of the pyrethroid insecticide lambda-cyhalothrin,ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 1 2008Chao Xu Abstract Chiral pollutants are receiving growing environmental concern due to differential biological activities of their enantio-mers. In the present study, enantiomeric separation of the pyrethroid insecticide lambda-cyhalothrin (LCT) was investigated by high-performance liquid chromatography (HPLC) using the columns of Chiralpak AD (amylase tris[3,5-dimethyl-phenylcarbamate]), Chiralpak AS (amylase tris[(S)-1-phenyl carbamate]), Chiralcel OD (cellulose tris[3,5-dimethylphenyl carbamate]), and Chiralcel OJ (cellulose tris[4-methyl benzoate]) with different chiral stationary phases. The differential toxicities of the enantiomers in aquatic systems were evaluated using the acute zebrafish (Danio rerio) toxicity test and the zebrafish embryo test. The enantiomers of LCT were separated completely on all the columns tested and detected by circular dichroism at 236 nm. Better separations were achieved at lower temperatures (e.g., 20°C) and lower levels of polar modifiers (,5%) in mobile phase. Ethanol was found to be a good modifier of the mobile phase for all the columns, although isopropanol acted better for the Chiralcel OD column. The (,)-enantiomer was >162 times more toxic than its antipode to zebrafish in the acute test. The embryo test indicated that the exposure to LCT enantioselectively induced crooked body, yolk sac edema, and pericardial edema and that the (,)-enantiomer was 7.2 times stronger than the (+)-enantiomer in 96-h mortality. The malformations were induced by the racemate and its (,)-enantiomer at lower concentrations tested (e.g., 50 ,g L,1), whereas the (+)-enantiomer induced malformations at relatively higher concentrations (,100 ,g L,1). These results suggest that the toxicological effects of chiral pesticides must be evaluated using their individual enantiomers. [source] Emission of legacy chlorinated pesticides from agricultural and orchard soils in British Columbia, CanadaENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 6 2006Terry F. Bidleman Abstract Air samples were collected above agricultural fields in the Fraser Valley and orchards in the Okanagan Valley, British Columbia, Canada, to investigate volatilization of organochlorine pesticides used in the past. Concentrations of pesticides in air were elevated over soils that contained higher residues. Soil/air fugacity ratios at sites with the higher soil residues were calculated relative to air sampled at 40 cm height and background air. The fugacity ratios in the first case indicated net volatilization or soil-air equilibrium for most compounds and occasional net deposition for p,p, -dichlorodiphenyldichloroethene (p,p, -DDE), whereas those in the second case showed a strong potential for net volatilization of all compounds. The enantiomer fraction (EF) of chiral compounds ,-hexachlorocyclohexane (,-HCH), trans -chlordane, cis -chlordane, and o,p, -DDT were determined in overlying air samples and soils. Enantiomer fractions in air corresponded to those in soils at fields in which soil concentrations were high but were decoupled from soil signatures at fields with low soil residues. Mean EFs in air sampled over soils were significantly (p < 0.001) nonracemic for ,-HCH and the chlordanes and agreed with published EFs in regional ambient air. The mean EF of o,p, -DDT for all air samples did not show a significant deviation from racemic EFs (p > 0.2), but EFs of individual samples reflected the ambivalent nature of o,p, -DDT degradation, sometimes preferring the (+) enantiomer and other times the (,) enantiomer. The study indicates that soils are continuing to emit "legacy" pesticides into the regional atmosphere. [source] Isomer selectivity in aquatic toxicity and biodegradation of bifenthrin and permethrinENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 8 2005Weiping Liu Abstract Synthetic pyrethroids are widely used insecticides, and contamination of surface aquatic ecosystems by pyrethroid residues from runoff is of particular concern because of potential aquatic toxicity. Pyrethroids also are chiral compounds consisting of multiple stereoisomers. In the present study, we evaluated the diastereomer and enantiomer selectivity of cis -bifenthrin (cis -BF) and permethrin (PM) in their aquatic toxicity and biodegradation. The 1R-cis enantiomer was the only enantiomer in cis -BF showing toxicity against Ceriodaphnia dubia. Incubation with pesticide-degrading bacteria showed that the trans diastereomer of PM was selectively degraded over the cis diastereomer, whereas the 1S-cis enantiomer in cis -BF or cis -PM was preferentially degraded over the corresponding 1R-cis enantiomer. The enantioselectivity was significantly greater for cis -PM than for cis -BF and also varied among different strains of bacteria. Isomer selectivity may be a common phenomenon in both aquatic toxicity and biodegradation of pyrethroids, and this should be considered when assessing ecotoxicological risks of these compounds in sensitive ecosystems. [source] Variations in ,-Hexachlorocyclohexane enantiomer ratios in relation to microbial activity in a temperate estuaryENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 7 2003Tiruponithura V. Padma Abstract Changes in the enantiomer ratios (ERs) of chiral pollutants in the environment are often considered evidence of biological alteration despite the lack of data on causal or mechanistic relationships between microbial parameters and ER values. Enantiomer ratios that deviate from 1:1 in the environment provide evidence for the preferential microbial degradation of one enantiomer, whereas ER values equal to 1 provide no evidence for microbial degradation and may mistakenly be interpreted as evidence that biodegradation is not important. In an attempt to link biological and geochemical information related to enantioselective processes, we measured the ERs of the chiral pesticide ,-hexachlorocyclohexane (,-HCH) and bacterial activity (normalized to abundance) in surface waters of the York River (VA, USA) bimonthly throughout one year. Despite lower overall ,-HCH concentrations, ,-HCH ER values were unexpectedly close to 1:1 in the freshwater region of the estuary with the highest bacterial activity. In contrast, ER values were nonracemic (ER , 1) and ,-HCH concentrations were significantly higher in the higher salinity region of the estuary, where bacterial activity was lower. Examination of these data may indicate that racemic environmental ER values are not necessarily reflective of a lack of biodegradation or recent input into the environment, and that nonenantioselective biodegradation may be important in certain areas. [source] Pharmacokinetics of Levetiracetam and Its Enantiomer (R)-,-ethyl-2-oxo-pyrrolidine acetamide in DogsEPILEPSIA, Issue 7 2001Nina Isoherranen Summary: ,Purpose: The new antiepileptic drug, levetiracetam (LEV, ucb LO59), is a chiral molecule with one asymmetric carbon atom whose anticonvulsant activity is highly enantioselective. The purpose of this study was to evaluate and compare the pharmacokinetics (PK) of LEV [(S)-,-ethyl-2-oxo-pyrrolidine acetamide] and its enantiomer (R)-,-ethyl-2-oxo-pyrrolidine acetamide (REV) after i.v. administration to dogs. This is the first time that the pharmacokinetics of both enantiomers has been evaluated. Methods: Optically pure LEV and REV were synthesized, and 20 mg/kg of individual enantiomers was administered intravenously to six dogs. Plasma and urine samples were collected until 24 h, and the concentrations of LEV and REV were determined by an enantioselective assay. The levels of 2-pyrrolidone- N -butyric acid, an acid metabolite of LEV and REV, were determined by high-performance liquid chromatography (HPLC). The data were used for PK analysis of LEV and REV. Results: LEV and REV had similar mean ± SD values for clearance; 1.5 ± 0.3 ml/min/kg and volume of distribution; 0.5 ± 0.1 L/kg. The half-life (t1/2) and mean residence time (MRT) of REV (t1/2, 4.3 ± 0.8 h, and MRT, 6.0 ± 1.1 h) were, however, significantly longer than those of LEV (t1/2, 3.6 ± 0.8 h, and MRT, 5.0 ± 1.2 h). The renal clearance and fraction excreted unchanged for LEV and REV were significantly different. Conclusions: In addition to the enantioselective pharmacodynamics, ,-ethyl-2-oxo-pyrrolidine acetamide has enantioselective PK. The enantioselectivity was observed in renal clearance. Because REV has more favorable PK in dogs than LEV, the higher antiepileptic potency of LEV is more likely due to intrinsic pharmacodynamic activity rather than to enantioselective PK. [source] quart -Feproline: Synthesis of a Very Rigid [3]Ferrocenophane-Derived Artificial Amino AcidEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 17 2008Ludger Tebben Abstract Starting from the ,-(dimethylamino)[3]ferrocenophane derivative 1, a short reaction sequence was developed to form a doubly anellated dihydropyrrole derivative 6 containing the ferrocenophane framework. Intermediate 6 was used for the synthesis of the (R,S,pS)-enantiomer of the rigid artificial amino acid "quart -Feproline". (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Preparation of Optically Active ,-Amino[3]ferrocenophanes , Building Blocks for Chelate Ligands in Asymmetric CatalysisEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 23 2003Patrick Liptau Treatment of 1,1,-diacetylferrocene (4) with dimethylamine and TiCl4 yielded the unsaturated dimethylamino-substituted [3]ferrocenophane product 5. Its catalytic hydrogenation gave the corresponding saturated [3]ferrocenophane system 6 (trans/cis , 7:1). The rac -[3]ferrocenophane amine 6 was partially resolved (to ca. 80% ee) by means of L - or D - O,O, -dibenzoyltartrate salt formation. Treatment of 4 with the pure (R)- or (S)-methyl(1-phenylethyl)amine (8)/TiCl4 gave the corresponding optically active unsaturated [3]ferrocenophane amines (R)-(+)- 9 and (S)-(,)- 9, respectively. Their catalytic hydrogenation again proceeded trans -selectively, giving the corresponding saturated diastereomeric [3]ferrocenophane amines (1R,3R,5R)- 10a and (1S,3S,5R)- 10b [starting from (R)- 9], their enantiomers ent - 10a and ent - 10b were obtained from (S)- 9, but with a poor asymmetric induction (10a/10b < 2:1). Quaternization of 6 (CH3I) followed by amine exchange using (R)- or (S)-methyl(1-phenylethyl)amine (8), respectively, proceeded with overall retention. Subsequent chromatographic separation gave the pure diastereoisomers (1R,3R,5R)- 10a and (1S,3S,5R)- 10b [from (R)- 8, ent - 10a and ent - 10b from (S)- 8] in > 60% yield. Subsequently, the benzylic (1-phenylethyl) auxiliary was removed from the nitrogen atom by catalytic hydrogenolysis to yield the enantiomerically pure (> 98%) ([3]ferrocenophanyl)methylamines (1R,3R)- 11 and (1S,3S)- 11, respectively, which were converted into the corresponding dimethylamino-substituted [3]ferrocenophanes (1R,3R)- 6 and (1S,3S)- 6. Each enantiomer from the following enantiomeric pairs was isolated in its pure form and characterized by X-ray diffraction: (R)- 9/(S)- 9; (1R,3R,5R)- 10a/(1S,3S,5S)- 10a; (1R,3R,5S)- 10b/(1S,3S,5R)- 10b; (1R,3R)- 11/(1S,3S)- 11. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Tetra- tert -butyltrioxabicyclo[3.3.1]nonadienedicarboxylic Acid: Optical Resolution, Absolute Configuration and Application in Chiral DiscriminationEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 19 2008Jennifer Kremsner Abstract The enantiopure bridged bis-dioxine 4, a dissymmetric dicarboxylic acid exhibiting axial chirality, can easily be synthesized and serve as host for separating and/or transporting chiral guest molecules. Racemic 4 gives with (R)- and (S)-1-phenylethylamine the corresponding pure diastereomeric salts 7 and 8. The absolut configuration of the diacid 4 in the diastereomeric salt 7 containing (R)-1-phenylethylamine was confirmed to be R by X-ray crystal structure analysis, which also confirmed its concave nature. Release of the acid-sensitive pure enantiomers (R)- 4 as well as (S)- 4 was achieved conveniently by use of dry flash-chromatography on silica. The CD spectrum shows a positive Cotton effect of the (S)-enantiomer at 206 nm. The enantiomeric purity was proved by 1H NMR discrimination of the diastereomeric salts with (R,R)-1,2-bis(4-methoxyphenyl)ethane-1,2-diamine as the base. The dicarboxylic acid (R)- 4 can be used as chiral auxiliary as demonstrated by the difficult resolution of racemicN,N,-di- tert -butyl-1,2-bis(4-methoxyphenyl)ethane-1,2-diamine 9.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Sulfoxide-Directed Stereocontrolled Access to 2H -Chromans: Total Synthesis of the (S,R,R,R)-Enantiomer of the Antihypertensive Drug NebivololEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 12 2008M. Carmen Carreño Abstract A homochiral sulfoxide-directed reductive deoxygenation of 2-(p -tolylsulfinyl)methyl-2-chromanols allows the stereoselective formation of 2H -chromans with up to 95:5 diastereoisomeric ratio. This new methodology was appliedin a short and convergent enantioselective synthesis ofthe (S,R,R,R)-enantiomer of the antihypertensive drugNebivolol.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Resolution of Racemic N -Benzyl ,-Amino Acids by Liquid-Liquid Extraction: A Practical Method Using a Lipophilic Chiral Cobalt(III) Salen Complex and Mechanistic StudiesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 7 2008Pawel Dzygiel Abstract The efficient resolution of racemic N -benzyl ,-amino acids (N -Bn-AA) has been achieved by a liquid-liquid extraction process using the lipophilic chiral salen,cobalt(III) complex [CoIII(3)(OAc)]. As a result of the resolution by extraction, one enantiomer (S) of the N -benzyl ,-amino acid predominated in the aqueous phase, while the other enantiomer (R) was driven into the organic phase by complexation to cobalt. The complexed amino acid (R) was then quantitatively released by a reductive (CoIII,,,CoII) counter-extraction with aqueous sodium dithionite or L -ascorbic acid in methanol. Thereductive cleavage allowed to recover the [CoII(3)] complex in good yield, which could be easily re-oxidized to[CoIII(3)(OAc)] with air/AcOH and reused with essentially no loss of reactivity and selectivity. Investigation on the nitrogen substitution indicates that the presence of a single benzyl group on the amino acid nitrogen is important to obtain high enantioselectivity in the extraction process. The kinetic vs. thermodynamic nature of the resolution process was also investigated with an enantiomeric exchange experiment, which shows that the liquid-liquid extraction with [CoIII(3)(OAc)] is an equilibrium process operating under thermodynamic control. In the absence of a suitable crystal structure of the [CoIII(3)(N -Bn-AA)] complexes, computational and spectroscopic studies were used to investigate how the N -benzyl ,-amino acids are accommodated in the "binding pocket" of the chiral cobalt complex. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] A Temporary Stereocentre Approach for the Stereodivergent Synthesis of Either Enantiomer of ,-MethyloctanalEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 33 2007D. Gangani Niyadurupola Abstract The aldol reaction of a chiral N -(acyl)oxazolidin-2-one with 2-methyleneoctanal or (E)-2-methyloct-2-enal affords chiral aldol products whose alkene functionalities were hydrogenated using Brown's or Wilkinson's catalyst to afford syn - or anti -selective products with excellent levels of diastereocontrol. Subsequent retro -aldol cleavage of these syn - or anti -adducts resulted in the formation of either (R)- or (S)-enantiomer of ,-methyloctanal with no racemisation occurring, which could be derivatised in-situ to afford chiral dithiane, alcohol or ,,,-unsaturated ester products in enantiopure form.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Synthesis of an Enantiomerically Pure Building Block for the Synthesis of Hydroporphyrins,EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 2 2007Genevieve Etornam Adukpo Abstract The enantiomerically pure pyrrolidine diester 4 is a useful building block for the synthesis of chiral hydroporphyrin compounds. Treatment of optically active aromatic amines with bislactone 5 gave pairs of N -alkylated lactam-lactone diastereomers 6 and 8. These diastereomers were separated by MPL chromatography and in the case of 8 they could be debenzylated to yield the enantiomerically pure lactam-lactone 7 and its enantiomer. The (,)-lactam-lactone enantiomer 7 was further transformed into building block 4.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Enantioselective Mukaiyama-Aldol Reaction of Pyruvates and 1-Phenyl- 1-trimethylsilyloxyethene Catalyzed by Lanthanide/Pybox ComplexesEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 23 2006Giovanni Desimoni Abstract The enantioselective Mukaiyama-aldol reaction between 1-phenyl-1-trimethylsilyloxyethene (1) and three pyruvates (2a,c) is catalyzed by the lanthanide triflate complexes of(4S,5S)-2,6-bis[5-phenyl-4-(triisopropylsilyloxy)methyl-1,3-oxazolin-2-yl]pyridine (3). The best catalysts are the LuIII - and ScIII -based complexes that give high yields of (S)- 4a,c and enantiomeric excesses up to 99.5,%. The LaIII -based complex favors the formation of the opposite enantiomer [77,% ee of (R)- 4c]. The rationale of the stereochemical outcome is proposed. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006) [source] | |||||||||||||||||||||||||||||||||||||