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Enantioselectivity
Kinds of Enantioselectivity Selected AbstractsEnantioselectivity 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] Enantioselectivity of alcohol-modified polymeric surfactants in micellar electrokinetic chromatographyELECTROPHORESIS, Issue 15 2003Jepkoech Tarus Abstract A novel method of modifying sodium undecanoyl- L -leucinate (SUL) micelles employed in chiral separation of analytes in micellar electrokinetic chromatography (MEKC) to enhance selectivity toward specific analytes is discussed. The current study aimed at modifying the SUL micelles by introducing different alcohols into the mono-SUL micelles. The micellar solutions were then polymerized in the presence of alcohols followed by postpolymerization extraction of the alcohols to yield alcohol-free polymeric surfactants (poly- L -SUL). The effects of hexanol (C6OH) and undecylenyl alcohol (C11OH) on micellar properties of this surfactant were investigated by use of surface tensiometry, fluorescence spectroscopy, pulsed field gradient-nuclear magnetic resonance (PFG-NMR), and MEKC. The surface tension and PFG-NMR studies indicated an increase in the critical micelle concentration (cmc) and micellar size upon increasing the alcohol concentration. Fluorescence measurements suggested that alcohols induce closely packed micellar structures. Coumarinic and benzoin derivatives, as well as (±)-1, 1'-binaphthyl-2,2'-dihydrogen phosphate (BNP) were used as test analytes for MEKC experiments. Examination of MEKC data showed remarkable resolutions and capacity factors of coumarinic derivatives obtained with modified poly- L -SUL as compared to the unmodified poly- L -SUL. Evaluation of fluorescence, PFG-NMR, and MEKC data suggest a strong correlation between the polarity and hydrodynamic radii of alcohol-modified micelles and the resolution of the test analytes. [source] Ruthenium Complexes Containing Chiral N-Donor Ligands as Catalysts in Acetophenone Hydrogen Transfer , New Amino Effect on EnantioselectivityEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 21 2005Montserrat Gómez Abstract New p -cymene ruthenium species containing chiral amino alcohols (1,3), primary (4,7) and secondary (8, 9) amino-oxazolines, were tested as catalysts in the hydrogen transfer of acetophenone, using 2-propanol as the hydrogen source. A remarkable effect on the enantioselectivity, but also on the activity, was observed depending on the amino-type oxazoline, Ru/8 and Ru/9 being low active and nonselective catalytic systems, in contrast to their primary counterpart Ru/5. Complexes containing amino-oxazolines (10,12) were prepared and fully characterized, both in solution and in solid state. The X-ray structure was determined for (SRu,RC)- 10. The diastereomeric ratios observed for complexes 10 and 11 were determined by 1H NMR and confirmed by means of structural modeling (semi-empirical PM3(tm) level). DFT theoretical calculations for the transition states involved in the hydrogen transfer process proved the important differences in their relative populations, which could justify the enantioselectivity divergences observed between primary and secondary amino-oxazoline ruthenium systems. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005) [source] DFT/MM Study on Copper-Catalyzed Cyclopropanation , Enantioselectivity with No Enthalpy BarrierEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 33 2008Galí Drudis-Solé Abstract The enantioselectivity in the reaction of [Cu(adam-box)(CHCO2Me)] {adam-box = 2,2,-isopropylidenebis[(4R)-(1-adamantyl)-2-oxazoline]} with Ph2C=CH2 was analyzed computationally by ONIOM(B3LYP:UFF) calculations. The lack of transition states in the potential-energy surface precludes the use of conventional approaches and requires the definition of reaction paths in an approximate Gibbs free-energy surface. The procedure is time consuming and intrinsically less accurate than the usual approaches based on enthalpic energy surfaces, but it produces results in reasonable agreement with experiment, which furthermore allow identification of the key interactions responsible for chiral discrimination.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] DFT Study of Brønsted Acid Catalyzed Nitroso Aldol Reaction Between Achiral Enamines and Nitrosobenzene: The Reason for Regio- and EnantioselectivityEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 25 2008Matsujiro Akakura Abstract The regio- and enantioselectivity of the nitroso aldol reaction between achiral enamines and nitrosobenzene catalyzed by chiral Brønsted acid catalysts (TADDOL or 1-naphthylglycolic acid) were investigated in experimental and theoretical studies. The use of a model involving a simple organic acid (MeOH or AcOH) revealed that the reaction was catalyzed by two or more molecules of the organic acid and that the transition-state structure encompassed several hydrogen bonds. The role of hydrogen bonding in the regioselectivity was also examined carefully. The enantioselectivity in the reaction catalyzed by chiral organic acids (S,S)-TADDOL and (S)-1-naphthylglycolic acid was also confirmed through computational study.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008) [source] Palladium-Catalyzed Formation of Cyclic Ethers , Regio-, Stereo- and Enantioselectivity of the ReactionEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 14 2007Anna Zawisza Abstract An efficient and stereoselective synthesis of 3-alkyl-3-hydroxymethyl-5-vinyltetrahydrofurans is described by the Pd0 -catalyzed cyclization of the methyl carbonates of ,,,-bis(hydroxymethyl)-,,,-unsaturated alcohols. The use of chiral ligands gave the corresponding THF derivatives in low to moderate enantiomeric ratios. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source] Chemo- and Enzyme-Catalyzed Reactions Revealing a Common Temperature-Dependent Dynamic Solvent Effect on EnantioselectivityHELVETICA CHIMICA ACTA, Issue 11 2003Gianfranco Cainelli The enantiomeric ratio E of enzyme-catalyzed (Candida antarctica lipase and lipase PS) and chemo-catalyzed (L -proline-based diamines) acylation reactions of 1-(naphthalen-2-yl)ethanol, 2-phenylpropanol, and 2-benzylpropane-1,3-diol is dependent on solvent and temperature. Plots of ln,E vs. 1/T showed the presence of inversion temperatures (Tinv). The Tinv values for the bio-catalyzed and the chemo-catalyzed reactions are fairly in agreement, and correspond as well to the TNMR values obtained by variable-temperature 13C-NMR experiments on the substrates in the same solvent of the resolution. This result demonstrates that clustering effects in the substrate solvation manage the chemical and the enzymatic enantioselectivity, and, moreover, that the solutesolvent cluster is always the real reacting species in solution for chemical as well as for enzymatic reactions. [source] On the Enantioselectivity of Transition Metal-Catalyzed 1,3-Cycloadditions of 2-Diazocyclohexane-1,3-dionesHELVETICA CHIMICA ACTA, Issue 9 2003Paul Müller The formal 1,3-cycloaddition of 2-diazocyclohexane-1,3-diones 1a,1d to acyclic and cyclic enol ethers in the presence of RhII -catalysts to afford dihydrofurans has been investigated. Reaction with a cis/trans mixture of 1-ethoxyprop-1-ene (13a) yielded the dihydrofuran 14a with a cis/trans ratio of 85,:,15, while that with (Z)-1-ethoxy-3,3,3-trifluoroprop-1-ene (13b) gave the cis -product 14b exclusively. The stereochemical outcome of the reaction is consistent with a concerted rather than stepwise mechanism for cycloaddition. The asymmetric cycloaddition of 2-diazocyclohexane-1,3-dione (1a) or 2-diazodimedone (=2-diazo-5,5-dimethylcyclohexane-1,3-dione; 1b) to furan and dihydrofuran was investigated with a representative selection of chiral, nonracemic RhII catalysts, but no significant enantioselectivity was observed, and the reported enantioselective cycloadditions of these diazo compounds could not be reproduced. The absence of enantioselectivity in the cycloadditions of 2-diazocyclohexane-1,3-diones is tentatively explained in terms of the Hammond postulate. The transition state for the cycloaddition occurs early on the reaction coordinate owing to the high reactivity of the intermediate metallocarbene. An early transition state is associated with low selectivity. In contrast, the transition state for transfer of stabilized metallocarbenes occurs later, and the reactions exhibit higher selectivity. [source] The Origin of the High Enantioselectivity in Asymmetric Cyclopropanation of Unfunctionalized OlefinsADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 11-12 2010Yiying Zheng Abstract The mechanism of the asymmetric Simmons,Smith cyclopropanation for unfunctionalized olefins was investigated using density functional theory (DFT) methods. The calculated results of model reactions showed that the coordinated Lewis acidic zinc halide ZnX2 (X=Cl, I) and/or halomethylzinc halide XZnCH2X in the catalyst play an important role in the enantioselectivity. The catalyst not only forms the ring with the substance in the reaction centre, but also establishes two steric repulsions that can lead to an explanation for the high enantioselectivity. Hence, these results highlight some important insights for the prerequisites of an effective catalyst and a proper substrate towards high enantioselectivity for this kind of reaction. [source] Effects of Methyl Substituents on the Activity and Enantioselectivity of Homobenzotetramisole-Based Catalysts in the Kinetic Resolution of AlcoholsADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 14-15 2009Yuhua Zhang Abstract Substitution of the tetrahydropyrimidine ring in the enantioselective acyl transfer catalyst homobenzotetramisole (HBTM) 6 with methyl groups exerts a dramatic influence on its performance in the kinetic resolution of secondary alcohols. The syn- 3-methyl analogue of HBTM (9a) has proved to be superior to the parent compound in terms of catalytic activity, enantioselectivity, and synthetic accessibility. [source] A Three-Dimensional Quanititative Structure-Activity Relationship (3D-QSAR) Model for Predicting the Enantioselectivity of Candida antarctica Lipase BADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 9 2009Paolo Braiuca Abstract Computational techniques involving molecular modeling coupled with multivariate statistical analysis were used to evaluate and predict quantitatively the enantioselectivity of lipase B from Candida antarctica (CALB). In order to allow the mathematical and statistical processing of the experimental data largely available in the literature (namely enantiomeric ratio E), a novel class of GRID-based molecular descriptors was developed (differential molecular interaction fields or DMIFs). These descriptors proved to be efficient in providing the structural information needed for computing the regression model. Multivariate statistical methods based on PLS (partial least square , projection to latent structures), were used for the analysis of data available from the literature and for the construction of the first three-dimensional quanititative structure-activity relationship (3D-QSAR) model able to predict the enantioselectivity of CALB. Our results indicate that the model is statistically robust and predictive. [source] Origin of Enantioselectivity in the Organocatalytic Reductive Amination of ,-Branched AldehydesADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 4 2009Tommaso Marcelli Abstract The reason for enantioselectivity in the reductive amination of ,-branched aldehydes was investigated. The relative energies of all the diastereomeric transition states for hydride transfer of a suitable computational model were calculated at the B3LYP/6-311+G(2d,2p) level of theory. Our calculations successfully reproduce and rationalize the experimentally observed stereochemical outcome of the reaction. [source] A Novel Cost-Effective Thiourea Bifunctional Organocatalyst for Highly Enantioselective Alcoholysis of meso -Cyclic Anhydrides: Enhanced Enantioselectivity by Configuration InversionADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 4 2009Su-Xi Wang Abstract A novel inexpensive thiourea bifunctional organocatalyst which can promote the highly enantioselective (up to 95% ee) alcoholysis of meso -cyclic anhydrides has been developed. Computational studies on the catalytic process as well as a synthetic application of this new catalyst are also presented. [source] Titanium(IV)/Tridentate BINOL Derivative as Catalyst for meso -Aziridine Ring-Opening Reactions: High Enantioselectivity, Strong Positive Non-Linear Effect and Structural CharacterizationADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 1-2 2009Rongmin Yu Abstract A titanium-based chiral Lewis acid was found to be effective for the ring-opening reactions of meso -aziridines with aniline nucleophiles. The products were generally isolated in high yields and with high to excellent enantioselectivity. The catalytic system was studied by X-ray single crystal analysis. In experiments on non-linear effects a strong non-linear effect of the catalyst system was observed. [source] A Protection Strategy Substantially Enhances Rate and Enantioselectivity in ,-Transaminase-Catalyzed Kinetic ResolutionsADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 6 2008Matthias Höhne Abstract The kinetic resolution of 3-aminopyrrolidine (3AP) and 3-aminopiperidine (3APi) with ,-transaminases was facilitated by the application of a protecting group concept. 1- N -Cbz-protected 3-aminopyrrolidine could be resolved with >99% ee at 50% conversion, the resolution of 1- N -Boc-3-aminopiperidine yielded 96% ee at 55% conversion. The reaction rate was up to 50-fold higher by using protected substrates. Most importantly, enantioselectivity increased remarkably after carbamate protection compared to the unprotected substrates (86 vs. 99% ee). Surprisingly, benzyl protection of 3AP had no influence on enantioselectivity. A possible explanation for this observation could be the different flexibility of the benzyl- or carbamate-protected 3AP as confirmed by NMR spectroscopy. [source] Titration and Assignment of Residues that Regulate the Enantioselectivity of Phenylacetone MonooxygenaseADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 8-9 2007Francesca Zambianchi Abstract Phenylacetone monooxygense (PAMO) from Thermobifida fusca was employed for the asymmetric oxidation of thioanisole (sulfooxidation) and of racemic 2-phenylpropionaldehyde (Baeyer,Villiger oxidation). A pH dependence of enantioselectivity was observed in both cases. Two different residues, with pKa values of 7.8±0.2 and 9.2±0.2, appeared to be responsible for the pH effects on PAMO enantioselectivity. The protonation of Arg337 and the FAD:C4a-hydroperoxide/FAD:C4a-peroxide equilibrium were identified as the major factors responsible for the fine-tuning of PAMO enantioselectivity in Baeyer,Villiger oxidation and sulfooxidation, respectively. [source] Non-Linear Effect of Modifier Composition on Enantioselectivity in Asymmetric Hydrogenation over Platinum MetalsADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 1-2 2003Wolf-Rüdiger Huck Abstract Prominent non-linear behavior was observed when mixtures of cinchona alkaloids were applied as chiral modifiers in enantioselective hydrogenations over Pt/Al2O3 and Pd/TiO2. The phenomenon is traced to differences in the strength and geometry of alkaloid adsorption on the metal surface. In ethyl pyruvate hydrogenation under close to ambient conditions the weaker adsorbing quinidine (QD) outperformed the generally preferred modifier cinchonidine (CD) and afforded the highest ee (96,98%) at 1,5,bar. In the partial hydrogenation of 4-methoxy-6-methyl-2-pyrone to the dihydro derivative 4 CD gave 73% ee to (S)- 4 and QD provided 72% ee to (R)- 4, and still the alkaloid mixture containing less than 5,mol,% CD afforded 15% ee to (S)- 4. This non-linear behavior may be advantageous in asymmetric synthesis as low purity chiral compounds can be applied as efficient modifiers for Pt or Pd. [source] Enantioselectivity of thalidomide serum and tissue concentrations in a rat glioma model and effects of combination treatment with cisplatin and BCNUJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 1 2007Susan Murphy Thalidomide is currently under evaluation as an anti-angiogenic agent in cancer treatment, alone and in combination with cytotoxic agents. Thalidomide is a racemate with known pharmacologic and pharmacokinetic enantioselectivity. In a previous study with thalidomide combination chemotherapy, we found evidence of anti-tumour synergy. In this study, we examined whether the synergy involved altered pharmacokinetics of thalidomide enantiomers. Adult female F344 rats were implanted with 9L gliosarcoma tumours intracranially, subcutaneously (flank), or both. Effectiveness of oral thalidomide alone, and with intraperitoneal BCNU or cisplatin combination chemotherapy, was assessed after several weeks treatment. Presumed pseudo steady-state serum, tumour and other tissues, collected after treatment, were assayed for R - and S -thalidomide by chiral HPLC. Both serum and tissue concentrations of R -thalidomide were 40,50% greater than those of S -thalidomide. Co-administration of BCNU or cisplatin with thalidomide did not alter the concentration enantioselectivity. Poor correlation of concentration with subcutaneous anti-tumour effect was found for individual treatments, and with all treatments for intracranial tumours. The consistency of the enantiomer concentration ratios across treatments strongly suggests that the favourable anti-tumour outcomes from interactions between thalidomide and the cytotoxic agents BCNU and cisplatin did not have altered enantioselectivity of thalidomide pharmacokinetics as their basis. [source] Enantioselectivity of Haloalkane Dehalogenases and its Modulation by Surface Loop Engineering,ANGEWANDTE CHEMIE, Issue 35 2010Zbynek Prokop Dr. Gezielte Mutationen der Oberflächenschleife von Halogenalkan-Dehalogenasen haben Auswirkungen auf die Enantiodiskriminierung. Die Temperaturabhängigkeit der Enantioselektivität (siehe lnE -1/T -Kurve) von ,-Bromalkanen kehrt sich bei einer Deletion der Oberflächenschleife um (rote Datenpunkte), was bei Einführung einer zusätzlichen Einzelpunktmutation wieder rückgängig gemacht wird; bei ,-Bromestern findet keine Änderung statt. [source] High-Throughput Method for Determining the Enantioselectivity of Enzyme-Catalyzed Hydroxylations Based on Mass Spectrometry,ANGEWANDTE CHEMIE, Issue 31 2010Yongzheng Chen Dr. Richtig schnell: Eine genaue, empfindliche und einfache Hochdurchsatzmethode zur Bestimmung des Produkt- ee -Werts enzymkatalysierter Hydroxylierungen (siehe Schema) beruht auf dem Einsatz enantiomerenreiner oder -angereichter deuterierter Substrate und dem massenspektrometrischen Nachweis. [source] Reversal of Enantioselectivity by Tuning the Conformational Flexibility of Phase-Transfer Catalysts,ANGEWANDTE CHEMIE, Issue 15 2010Ming-Qing Hua Eine Umkehrung der Enantioselektivität wurde bei der konjugierten Addition von Nitroalkanen an Chalkone beobachtet, wenn spirocyclische quartäre Ammoniumsalze auf Binol-Basis als Phasentransferkatalysatoren eingesetzt wurden. Neuartige chirale Katalysatoren wurden entworfen und synthetisiert (siehe Struktur). [source] Quantification of a CH,, Interaction Responsible for Chiral Discrimination and Evaluation of Its Contribution to Enantioselectivity,ANGEWANDTE CHEMIE, Issue 42 2009Romen Carrillo Dr. Schwach, aber nicht unerheblich: Die starke Chiralitätserkennung durch einen neuen Rezeptor für die Ammoniumsalze aromatischer ,-Aminosäuremethylester beruht vor allem auf der CH-,-Wechselwirkung, einer der schwächsten nichtkovalenten Wechselwirkungen (siehe Bild). Die Wechselwirkung wurde quantifiziert, und ihr Beitrag zur Chiralitätserkennung wurde ermittelt. [source] Reversal of Enantioselectivity between the Copper(I)- and Silver(I)-Catalyzed 1,3-Dipolar Cycloaddition Reactions Using a Brucine-Derived Amino Alcohol Ligand,ANGEWANDTE CHEMIE, Issue 40 2009Young Kim Dr. Unterschiedliche Enantioselektivitäten werden in Reaktionen mit dem Aminoalkohol 1 als einziger Chiralitätsquelle erhalten, weil dieser Ligand auf unterschiedliche Weise an CuI und AgI bindet. Azomethin-Ylide gehen mit substituierten tert -Butylacrylaten hoch enantio- und diastereoselektive 1,3-dipolare Cycloadditionen ein, die beide Enantiomere der Pyrrolidin-Produkte ergeben (siehe Schema). [source] Species differences in enantioselective 2-oxidations of RS-8359, a selective and reversible MAO-A inhibitor, and cinchona alkaloids by aldehyde oxidaseBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 3 2006Kunio Itoh Abstract The 2-oxidation activity on the pyrimidine ring of RS-8359, a MAO-A inhibitor, is the major metabolic pathway catalysed by aldehyde oxidase. This study investigated the species differences in the 2-oxidation activity by using liver cytosolic fractions from rats, mice, guinea-pigs, rabbits, dogs, monkeys and humans. The Vmax/Km value for the (S)-enantiomer of RS-8359 was extremely high in monkeys and humans, moderate in guinea-pigs, and low in rats and mice. Dogs were deficient in 2-oxidation activity. The (R)-enantiomer was only oxidized at a very low rate in guinea-pigs, monkeys and humans, and not oxidized in rats, mice and rabbits. Thus, marked species differences and enantioselectivity were obvious for the 2-oxidation of the (S)-enantiomer of RS-8359. The in vitro results were in good accordance with previously reported in vivo excretion data of the 2-keto metabolite and the non-detectable plasma concentrations of the (S)-enantiomer in monkeys and humans after administration of racemic RS-8359. Enantioselectivity was also observed for the oxidation of cinchona alkaloids catalysed by aldehyde oxidase. Among the four cinchona alkaloids studied, the oxidation activity of cinchonidine, which has no substituents at the 6-hydroxy group but bears (8S,9R)-configurations, was highest. As opposed to the (S)-enantiomer, an extremely high catalytic activity of cinchonidine was confirmed in rabbits, but not in monkeys or humans. Rabbit liver aldehyde oxidase was suggested to have characteristic properties around the active site. Copyright © 2006 John Wiley & Sons, Ltd. [source] A Novel Genetic Selection System for Improved Enantioselectivity of Bacillus subtilis Lipase ACHEMBIOCHEM, Issue 7 2008Ykelien L. Boersma Dr. Abstract In directed evolution experiments, success often depends on the efficacy of screening or selection methods. Genetic selections have proven to be extremely valuable for evolving enzymes with improved catalytic activity, improved stability, or with altered substrate specificity. In contrast, enantioselectivity is a difficult parameter to select for. In this study, we present a successful strategy that not only selects for catalytic activity, but for the first time also for enantioselectivity, as demonstrated by the selection of Bacillus subtilis lipase A variants with inverted and improved enantioselectivity. A lipase mutant library in an aspartate auxotroph Escherichia coli was plated on minimal medium that was supplemented with the aspartate ester of the desired enantiomer (S)-(+)-1,2- O -isopropylidene- sn -glycerol. To inhibit growth of less enantioselective variants, a covalently binding phosphonate ester of the opposite (R)-(,)-1,2- O -isopropylidene- sn -glycerol enantiomer was added as well. After three selection rounds in which the selection pressure was increased by raising the phosphonate ester concentration, a mutant was selected with an improved enantioselectivity increased from an ee of ,29.6,% (conversion 23.4,%) to an ee of +73.1,% (conversion 28.9,%) towards the (S)-(+)-enantiomer. Interestingly, its amino acid sequence showed that the acid of the catalytic triad had migrated to a position further along the loop that connects ,7 and ,E; this shows that the position of the catalytic acid is not necessarily conserved in this lipase. [source] Water Exclusion and Enantioselectivity in Catalysis,CHEMBIOCHEM, Issue 10 2006Ronald Breslow Prof. Dr. High and dry. Enzymes perform catalyses in the interior of the protein, which is not aqueous in character. Polyethylenimine enzyme mimics with a hydrophobic core also achieve high rates by excluding water. Two different approaches to the synthesis of such artificial enzymes with chirally attached side chains are described, as well as the use of these enzymes in performing biomimetic transaminations with chiral selectivity [source] Learning from Directed Evolution: Theoretical Investigations into Cooperative Mutations in Lipase EnantioselectivityCHEMBIOCHEM, Issue 2 2004Marco Bocola Dr. Abstract Molecular modeling with classical force-fields has been used to study the reactant complex and the tetrahedral intermediate in lipase-catalyzed ester hydrolysis in 20 enzyme/substrate combinations. The R and S enantiomers of,-methyldecanoic acid ester served as substrates for the wild-type lipase from Pseudomonas aeruginosa and nine selected mutants. After suitable preparation of initial structures from an available wild-type crystal structure, each system was subjected to 1 ns CHARMM force-field molecular dynamics simulations. The resulting geometric and energetic changes allow interpretation of some experimentally observed effects of mutations, particularly with regard to the "hot spots" at residues 155 and 162. The replacement S155F enhances S enantiopreference through a steric relay involving Leu162. The double mutation S53P + L162G improves S enantioselectivity by creating a new binding pocket for the S enantiomer with an additional stabilizing hydrogen bond to His83. The simulations provide insight into remote and cooperative effects of mutations. [source] ChemInform Abstract: Effect of Borane Source on the Enantioselectivity in the Enantiopure Oxazaborolidine-Catalyzed Asymmetric Borane Reduction of Ketones.CHEMINFORM, Issue 9 2008Xiao Wang Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a "Full Text" option. The original article is trackable via the "References" option. [source] Increased Enantioselectivity and Remarkable Acceleration of Lipase-Catalyzed Transesterification by Using an Imidazolium PEG,Alkyl Sulfate Ionic Liquid.CHEMINFORM, Issue 14 2007Toshiyuki Itoh Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] Enantioselective Aza-Diels,Alder Reaction Catalyzed by a Chiral Broensted Acid: Effect of the Additive on the Enantioselectivity.CHEMINFORM, Issue 21 2006Takahiko Akiyama Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF. [source] | |||||||||||||||||||||||||||||||