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Stereoselectivity
Kinds of Stereoselectivity Selected AbstractsMetal-Controlled Stereoselectivity in Complex Formation: Assembly of Tetranuclear Copper(I) Complexes with Four Stereogenic Nitrogen Donor Functions in all-(R) and all-(S) ConfigurationsEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 9 2003Jörg Schneider Abstract The reaction of N,N, -dialkyl-3,7-diazanonane-1,9-dithiolate (NR2S2) ligands (R = Me, Et) with monovalent copper resulted in the formation of the chiral complexes [Cu4(NMe2S2)2] (1) and [Cu4(NEt2S2)2] (2) which were characterised by means of X-ray diffraction and spectroscopic techniques. They contain copper atoms in both linear {S,Cu,S} fragments, which act as linkers between mononuclear [Cu(NR2S2)], subsites, and in {CuS2N2} units within these building blocks, which can be described as incomplete coordination octahedra of unusual design. Due to favourable interplay between the spatial demands of the ligand system and the electronic requirements of the copper atom, the nitrogen donor atoms within the [Cu(NR2S2)], metallo ligands are restricted to identical absolute configurations. The combination of two [Cu(NR2S2)], metallo ligands with two further CuI ions to give the tetranuclear complexes 1 or 2 via S,Cu,S bridges underlies stereochemical control, resulting in optically active systems with (R,R,R,R) and (S,S,S,S) configurations. Consequently, metallo ligands in their enantiomeric forms cannot combine via S,Cu,S bridges to form optically inactive meso complexes with the (R,R,S,S) configuration. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003) [source] Enhanced Activity and Stereoselectivity of Polystyrene-Supported Proline-Based Organic Catalysts for Direct Asymmetric Aldol Reaction in WaterEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 31 2009Michelangelo Gruttadauria Abstract Several polystyrene-supported proline dipeptides and a prolinamide derivative were prepared by thiol,ene coupling. These materials were used as catalysts for the direct asymmetric aldol reaction in water, and results compared with unsupported catalysts in water. Such an approach gave more active or stereoselective catalysts compared to the unsupported compounds, showing that our immobilization procedure may be useful to develop catalytic materials with enhanced performance. Moreover, these catalysts can be recovered and reused for at least nine times without loss of activity or can be easily regenerated when their activity has decreased. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Synthesis of New ,-(Polyfluoroalkyl)-,-hydroxy-,-amino AcidsEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 29 2009Nataliya A. Tolmacheva Abstract New ,-(polyfluoroalkyl)-,-hydroxy-,-amino acids were synthesized from the corresponding starting 3-(benzoylamino)-6-(polyfluoroalkyl)-2H -pyran-2-ones. The key step of the synthesis was the hydrogenation of the pyrone ring. Stereoselectivity and yields depended dramatically on the reaction conditions and the nature of the polyfluoroalkyl group. Various conditions were used for the preparation of both mixtures of diastereomers and pure diastereomers of the target amino acids. The obtained ,-(polyfluoroalkyl)-,-hydroxy-,-amino acids are of interest as analogues of 2-amino-5-hydroxyvaleric acid and glutamic acid.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009) [source] Val-Ala Dipeptide Isosteres by Hydrocyanation of ,,-Amino ,,,-Unsaturated Ketones , Control of Stereoselectivity by the N -Protecting GroupEUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 10 2003Fabio Benedetti Abstract Three diastereoisomeric hydroxyethylene isosters of the Val-Ala dipeptide were synthesized from ,,,-unsaturated ketones 1 derived from N -Boc- and N,N -dibenzyl- L -valine. The enones were hydrocyanated with diethylaluminum cyanide to give the corresponding ,-cyano ketones with the stereoselectivity depending on the protecting group. N -Boc protected enone 1a gave a 1:1 mixture of anti and syn adducts 4a, 5a while the corresponding N,N -dibenzyl compound 1c gave a 6:1 mixture of anti, syn adducts 4c, 5c. Borohydride reduction of the resulting cyano ketones is also controlled by the protecting group, resulting in opposite stereoselectivities for N -Boc and N,N -dibenzyl compounds. The cyano alcohols thus obtained were converted, in several steps, into two series of enantiomerically pure hydroxyethylene isosters of the Val-Ala dipeptide. In the first series the hydroxy group and the N -terminal of the isoster are internally protected through the formation of an oxazolidine; in the second series the hydroxy group and the C-terminal are protected as lactone. Two oxazolidines (28, 29), corresponding to syn,syn and syn,anti 4-hydroxy-5-amino acid isosters, and three lactones (23,25), corresponding to syn,syn, syn,anti, and anti,anti isosters were obtained by this approach. (© Wiley-VCH Verlag GmbH & Co KGaA, 69451 Weinheim, Germany, 2003) [source] The allene oxide cyclase family of Arabidopsis thaliana , localization and cyclizationFEBS JOURNAL, Issue 10 2008Florian Schaller Jasmonates are derived from oxygenated fatty acids (oxylipins) via the octadecanoid pathway and are characterized by a pentacyclic ring structure. They have regulatory functions as signaling molecules in plant development and adaptation to environmental stress. Recently, we solved the structure of allene oxide cyclase 2 (AOC2) of Arabidopsis thaliana, which is, together with the other three AOCs, a key enzyme in the biosynthesis of jasmonates, in that it releases the first cyclic and biologically active metabolite , 12-oxo-phytodienoic acid (OPDA). On the basis of models for the bound substrate, 12,13(S)-epoxy-9(Z),11,15(Z)-octadecatrienoic acid, and the product, OPDA, we proposed that a conserved Glu promotes the reaction by anchimeric assistance. According to this hypothesis, the transition state with a pentadienyl carbocation and an oxyanion is stabilized by a strongly bound water molecule and favorable ,,, interactions with aromatic residues in the cavity. Stereoselectivity results from steric restrictions to the necessary substrate isomerizations imposed by the protein environment. Here, site-directed mutagenesis was used to explore and verify the proposed reaction mechanism. In a comparative analysis of the AOC family from A. thaliana involving enzymatic characterization, in vitro import, and transient expression of AOC,enhanced green fluorescent protein fusion proteins for analysis of subcellular targeting, we demonstrate that all four AOC isoenzymes may contribute to jasmonate biosynthesis, as they are all located in chloroplasts and, in concert with the allene oxide synthase, they are all able to convert 13(S)-hydroperoxy-9(Z),11(E),15(Z)-octadecatrienoic acid into enantiomerically pure cis(+)-OPDA. [source] Stereoselectivity in the Rhodium-Catalysed Reductions of Non-Conjugated DienesADVANCED SYNTHESIS & CATALYSIS (PREVIOUSLY: JOURNAL FUER PRAKTISCHE CHEMIE), Issue 9 2009Bao Nguyen Abstract The stereochemical course of rhodium-catalysed addition of hydrogen and catecholborane to bicyclo[2.2.1]heptadiene, and of hydrogen to a range of cyclic dienes has been analysed. For hydroboration, the overall catalytic reaction possesses exo -selectivity, but the initial step is endo -selective. For hydrogenation (deuteration), the first step may occur with either exo- or endo- selectivity, depending on the structure of the diene. This enables a distinction to be made between pathways involving prior dissociation of the diene, and direct addition to the complexed diene without full dissociation. The relative ease of hydrogenation of the first and second double bonds varies markedly with reactant structure, and also depends on the choice of catalyst ligands. For dicyclopentadiene, hydrogenation of the cyclopentene double bond is accompanied by rapid alkene isomerisation, as revealed by deuterium addition. The asymmetric hydrogenation of acyclic skipped meso -dienes is reported, demonstrating control of relative rates of the two sequential steps, with ees of up to 53% after the first reduction. [source] Dendritic Amplification of Stereoselectivity of a Prolinamide-Catalyzed Direct Aldol ReactionISRAEL JOURNAL OF CHEMISTRY, Issue 1 2009Kazuhiko Mitsui Isomeric "compact" and "expanded" dendrimers functionalized with L -prolinamide catalytic units at the periphery were compared as catalysts to monomer controls in the organocatalytic direct aldol condensation. A positive dendritic effect that amplifies the stereoselectivity of the direct aldol condensation was observed for dendrimers 3 and 4, compared with lower molecular weight catalysts L -prolinani-lide 1 and G1 dendron 2. The difference in the compactness between 3 and 4 appears to have less impact on the stereoselectivity than the preorganized multivalency of the dendritic catalysts. [source] Stereoselectivity of Pseudomonas cepacia lipase toward secondary alcohols: A quantitative modelPROTEIN SCIENCE, Issue 6 2000Tanja Schulz Abstract The lipase from Pseudomonas cepacia represents a widely applied catalyst for highly enantioselective resolution of chiral secondary alcohols. While its stereopreference is determined predominantly by the substrate structure, stereoselectivity depends on atomic details of interactions between substrate and lipase. Thirty secondary alcohols with published E values using P. cepacia lipase in hydrolysis or esterification reactions were selected, and models of their octanoic acid esters were docked to the open conformation of P. cepacia lipase. The two enantiomers of 27 substrates bound preferentially in either of two binding modes: the fast-reacting enantiomer in a productive mode and the slow-reacting enantiomer in a nonproductive mode. Nonproductive mode of fast-reacting enantiomers was prohibited by repulsive interactions. For the slow-reacting enantiomers in the productive binding mode, the substrate pushes the active site histidine away from its proper orientation, and the distance d(HN, , Oalc) between the histidine side chain and the alcohol oxygen increases. d(HN, , Oalc) was correlated to experimentally observed enantioselectivity: in substrates for which P. cepacia lipase has high enantioselectivity (E > 100), d(HN, , Oalc) is>2.2 Å for slow-reacting enantiomers, thus preventing efficient catalysis of this enantiomer. In substrates of low enantioselectivity (E < 20), the distance d(HN, , Oalc) is less than 2.0 Å, and slow- and fast-reacting enantiomers are catalyzed at similar rates. For substrates of medium enantioselectivity (20 < E< 100), d(HN, , Oalc) is around 2.1 Å. This simple model can be applied to predict enantioselectivity of P. cepacia lipase toward a broad range of secondary alcohols. [source] Enamine versus Oxazolidinone: What Controls Stereoselectivity in Proline-Catalyzed Asymmetric Aldol Reactions?,ANGEWANDTE CHEMIE, Issue 36 2010Akhilesh Auf dem rechten Wege: Ein Vergleich der Oxazolidinon- und Enamin-Pfade enantioselektiver Aldolreaktionen mithilfe von Dichtefunktional- und Übergangszustandsrechnungen offenbart, dass der Oxazolidinon-Pfad nicht das richtige stereochemische Ergebnis liefert (siehe Bild), der Enamin-Pfad hingegen schon. [source] Building Stereoselectivity into a Chemoselective Ring-Opening Metathesis Polymerization Catalyst for Alternating Copolymerization,ANGEWANDTE CHEMIE, Issue 22 2010Sebastian Torker Immer abwechselnd: Rutheniumkomplexe mit asymmetrischen zweizähnigen Phosphanliganden, die zwei unterschiedlich große Substituenten enthalten (grüne Kugeln), setzen Norbornen und Cycloocten in der Ringöffnungsmetathese-Polymerisation (ROMP) zu einem vollständig alternierenden Copolymer um. Das E/Z -Verhältnis lässt sich durch Variation des Raumbedarfs des Arensulfonatliganden (blaues Rechteck) systematisch verändern. [source] Microseparation techniques for the study of the enantioselectivity of drug,plasma protein bindingBIOMEDICAL CHROMATOGRAPHY, Issue 3 2009Laura Escuder-Gilabert Abstract Stereoselectivity in protein binding can have a significant effect on the pharmacokinetic and pharmacodynamic properties of chiral drugs. The investigation of enantioselectivity of drugs in their binding with human plasma proteins and the identification of the molecular mechanisms involved in the stereodiscrimination by the proteins represent a great challenge for clinical pharmacology. In this review, the separation techniques used for enantioselective protein binding experiments are described and compared. An overview of studies on enantiomer,protein interactions, enantiomer,enantiomer interactions as well as chiral drug,drug interactions, including allosteric effects, is presented. The contribution of individual plasma proteins to the overall enantioselective binding and the animal species variability in drug,plasma protein binding stereoselectivity are reviewed. Copyright © 2008 John Wiley & Sons, Ltd. [source] Stereoselective halofantrine and desbutylhalofantrine disposition in the rat: cardiac and plasma concentrations and plasma protein bindingBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 1 2002Dion R. Brocks Abstract Halofantrine (HF) is a chiral antimalarial drug known to cause cardiac arrhythmias in susceptible patients. In this study, the cardiac uptake and plasma protein binding of HF and desbutylhalofantrine (DHF) enantiomers were examined in the rat. Rats were given 2 mg/kg of either HF HCl or DHF HCl intravenously, then sacrificed at various times after dosing. Specimens were assayed using stereospecific methods. Uptake of HF and DHF enantiomers into heart was rapid. Substantial concentrations of both HF and DHF enantiomers were observed in rat heart, with stereoselectivity being noted for both in plasma and heart. Stereoselectivity was more pronounced for HF (AUC (+):(,) ratio= 1.58) than DHF (AUC (+):(,) ratio =1.16) in heart tissue. Heart:plasma AUC ratios of 6.8,8.0, and 9.3,21, were observed for HF and DHF enantiomers, respectively, indicating that DHF has greater cardiac uptake than HF itself. Plasma protein binding was extensive for both HF and DHF (>99.95%), and was stereoselective for DHF, with a 38% higher unbound fraction for (,)-DHF than antipode. In contrast, binding of HF enantiomers was nonstereoselective. The lower degree of stereoselectivity for DHF in heart tissues was attributable to its greater stereoselectivity in plasma protein binding. Copyright © 2002 John Wiley & Sons, Ltd. [source] ChemInform Abstract: Sequential Synthesis of (E)-,,,-Unsaturated Primary Amides with Complete Stereoselectivity.CHEMINFORM, Issue 38 2010Jose M. Concellon No abstract is available for this article. [source] Chemo- and Stereoselectivity of the Reaction of Aromatic Aldehydes with Triphenylphosphine and Trichloroacetic Acid Derivatives.CHEMINFORM, Issue 40 2006E. D. Matveeva 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] Stereoselectivity of Asymmetric Strecker Synthesis in a Cyclohexane System: Synthesis of Optically Active cis- and trans-1-Amino-2-hydroxycyclohexane-1-carboxylic Acids.CHEMINFORM, Issue 38 2006Tetsuro Shinada 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] Chemo- and Stereoselectivity in Titanium-Mediated Regioselective Ring-Opening Reaction of Epoxides at the More Substituted Carbon.CHEMINFORM, Issue 44 2005Tetsuaki Tanaka Abstract For Abstract see ChemInform Abstract in Full Text. [source] One-Pot Synthesis of Helical Aromatics: Stereoselectivity, Stability Against Racemization, and Assignment of Absolute Configuration Assisted by Experimental and Theoretical Circular Dichroism.CHEMINFORM, Issue 12 2005Masashi Watanabe Abstract For Abstract see ChemInform Abstract in Full Text. [source] Ring Closing Enyne Metathesis: Control over Mode Selectivity and Stereoselectivity.CHEMINFORM, Issue 8 2005Eric C. Hansen Abstract For Abstract see ChemInform Abstract in Full Text. [source] Diastereoselectivity in [2, + 2,] Photocycloaddition of Cholesteryl Cinnamate to Methyl 9-Phenanthrenecarboxylate: Control of the Stereoselectivity in Liquid Crystalline Phase.CHEMINFORM, Issue 52 2004Hajime Maeda Abstract For Abstract see ChemInform Abstract in Full Text. [source] A Study on the Regio- and Stereoselectivity in Palladium-Catalyzed Cyclizations of Alkenes and Alkynes Bearing Bromoaryl and Nucleophilic Groups.CHEMINFORM, Issue 34 2004Didier Bruyere Abstract For Abstract see ChemInform Abstract in Full Text. [source] Probing the Stereoselectivity of the Heck Arylation of Endocyclic Enecarbamates with Diazonium Salts.CHEMINFORM, Issue 24 20035R)-Phenylproline Methyl Ester, Concise Syntheses of (2S, Schramm, s C-Azanucleoside. Abstract For Abstract see ChemInform Abstract in Full Text. [source] Partial Reduction of 3-Heteroatom Substituted 2-Furoic Acids: The Role of an ortho Group in Viability and Stereoselectivity.CHEMINFORM, Issue 2 2003Timothy J. Donohoe Abstract For Abstract see ChemInform Abstract in Full Text. [source] ChemInform Abstract: On the Stereoselectivity of the Synthesis of 1-Hydroxymethyl-4-phenylsulfonylbuta-1,3-dienes from ,,y-Unsaturated Sulfones.CHEMINFORM, Issue 39 2001David Diez Martin Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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] ChemInform Abstract: New Insights into the endo-exo Stereoselectivity of the Intramolecular Diels,Alder Reaction of 1,3,8-Nonatrienes.CHEMINFORM, Issue 10 2001Michael J. Lilly Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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] The Effect of Counterion/Ligand Interplay on the Activity and Stereoselectivity of Palladium(II),Diimine Catalysts for CO/p -Methylstyrene CopolymerizationCHEMISTRY - A EUROPEAN JOURNAL, Issue 5 2007Barbara Binotti Dr. Abstract The catalytic activity and stereoselectivity of complexes [Pd(,1,,2 -C8H12OMe)(ArNC(R,)C(R,)NAr)]X in the copolymerization of CO and p -methylstyrene have been correlated with their interionic structure in solution and in the solid state, as determined by 19F,1H-HOESY NMR spectroscopy and X-ray diffraction studies, respectively. The highest productivity is obtained with unhindered diimine ligands bearing electron-donating substituents and with the least coordinating counterion. Copolymers with a microstructure ranging from atactic to predominantly isotactic are obtained. The degree of isotacticity increases as the steric hindrance in the apical positions and the coordinating ability of the counterion increase. The counterion is located close to the diimine in both solution and the solid state but it moves toward the palladium as the steric hindrance in the apical positions decreases. When the latter is small the counterion competes with the substrate for apical coordination, and consequently it affects the productivity. In the case of ortho -dimethyl-substituted ligands the counterion is confined in the back, above the NC(R,)C(R,)N moiety, and does not affect the productivity. However, it contributes to increasing the stereoregularity of the copolymer by making the aryl moieties more rigid. With R,=Me and Ar=o -Me2C6H3 an ll of 81,% and 72,% was obtained with X,=CF3SO3, or BArF,, respectively. The isotacticity of the copolymers produced by ortho -monosubstituted catalysts depends greatly on the counterion and ranges from 30,% to 59,% with X,=BArF, and X,=CF3SO3,, respectively, with Ar=o -EtC6H4 and R,=Me. Based on the interionic structural results, this effect can be explained by a greater reduction of the copolymerization rate of Cs -symmetric isomers with respect to their C2 -symmetric counterparts. [source] Aldol Additions of Dihydroxyacetone Phosphate to N -Cbz-Amino Aldehydes Catalyzed by L -Fuculose-1-Phosphate Aldolase in Emulsion Systems: Inversion of Stereoselectivity as a Function of the Acceptor AldehydeCHEMISTRY - A EUROPEAN JOURNAL, Issue 5 2005Laia Espelt Dr. Abstract The potential of L -fuculose-1-phosphate aldolase (FucA) as a catalyst for the asymmetric aldol addition of dihydroxyacetone phosphate (DHAP) to N -protected amino aldehydes has been investigated. First, the reaction was studied in both emulsion systems and conventional dimethylformamide (DMF)/H2O (1:4 v/v) mixtures. At 100,mM DHAP, compared with the reactions in the DMF/H2O (1:4) mixture, the use of emulsion systems led to two- to three-fold improvements in the conversions of the FucA-catalyzed reactions. The N -protected aminopolyols thus obtained were converted to iminocyclitols by reductive amination with Pd/C. This reaction was highly diastereoselective with the exception of the reaction of the aldol adduct formed from (S)- N -Cbz-alaninal, which gave a 55:45 mixture of both epimers. From the stereochemical analysis of the resulting iminocyclitols, it was concluded that the stereoselectivity of the FucA-catalyzed reaction depended upon the structure of the N -Cbz-amino aldehyde acceptor. Whereas the enzymatic aldol reaction with both enantiomers of N -Cbz-alaninal exclusively gave the expected 3R,4R configuration, the stereochemistry at the C-4 position of the major aldol adducts produced in the reactions with N -Cbz-glycinal and N -Cbz-3-aminopropanal was inverted to the 3R,4S configuration. The study of the FucA-catalyzed addition of DHAP to phenylacetaldehyde and benzyloxyacetaldehyde revealed that the 4R product was kinetically favored, but rapidly disappeared in favor of the 4S diastereoisomer. Computational models were generated for the situations before and after CC bond formation in the active site of FucA. Moreover, the lowest-energy conformations of each pair of the resulting epimeric adducts were determined. The data show that the products with a 3R,4S configuration were thermodynamically more stable and, therefore, the major products formed, in agreement with the experimental results. [source] Origin of the ,-Facial Stereoselectivity in the Addition of Nucleophilic Reagents to Chiral Aliphatic Ketones as Evidenced by High-Level Ab,Initio Molecular-Orbital CalculationsCHEMISTRY - AN ASIAN JOURNAL, Issue 6 2006Osamu Takahashi Dr. Abstract Ab,initio molecular-orbital (MO) calculations were carried out, at the MP2/6-311++G(d,p)//MP2/6-31G(d) level, to investigate the conformational Gibbs energy of alkyl 1-cyclohexylethyl ketones, cyclo- C6H11CHCH3COR (R=Me, Et, iPr, and tBu). In each case, one of the equatorial conformations was shown to be the most stable. Conformers with the axial CHCH3COR group were also shown to be present in an appreciable concentration. Short CH,,,CO and CH,,,OC distances were found in each stable conformation. The result was interpreted on the grounds of CH,,,,(CO) and CH,,,O hydrogen bonds, which stabilize the geometry of the molecule. The ratio of the diastereomeric secondary alcohols produced in the nucleophilic addition to cyclo- C6H11CHCH3COR was estimated on the basis of the conformer distribution. The calculated result was consistent with the experimental data previously reported: the gradual increase in the product ratio (major/minor) along the series was followed by a drop at R=tBu. The energy of the diastereomeric transition states in the addition of LiH to cyclo- C6H11CHCH3COR was also calculated for R=Me and tBu. The product ratio did not differ significantly in going from R=Me to tBu in the case of the aliphatic ketones. This is compatible with the above result calculated on the basis of the conformer distribution. Thus, the mechanism of the ,-facial selection can be explained in terms of the simple premise that the geometry of the transition state resembles the ground-state conformation of the substrates and that the nucleophilic reagent approaches from the less-hindered side of the carbonyl , face. [source] Stereoselective binding of human serum albuminCHIRALITY, Issue 3 2006Victor Tuan Giam Chuang Abstract Stereoselectivity in binding can have a significant effect on the drug disposition such as first-pass metabolism, metabolic clearance, renal clearance, and protein and tissue binding. Human serum albumin (HSA) is able to stereoselectively bind a great number of various endogenous and exogenous compounds. Various experimental data suggested that the two major drug-binding cavities, namely, site I and site II, do not seem to be the stereoselective binding sites of HSA. Stereoselective binding of HSA under disease conditions such as renal and hepatic diseases was found to be enhanced. In addition, site-to-site displacement of a site II-specific drug by another site II-specific drug was found to be stereoselective, too. Endogenous compounds such as long-chain fatty acids and uremic toxins are likely to cause combined direct and cascade effects that contribute to the preferential binding of a particular drug enantiomer. Taking together the findings of other studies, it is highly possible that the stereoselective binding site exists at the interface of the subdomains. © 2006 Wiley-Liss, Inc. Chirality [source] Stereoselectivity in formation of oxacephams from 1,3-alkylidene-threitols,CHIRALITY, Issue 7 2004Katarzyna Borsuk Abstract The [2+2]cycloaddition of CSI to the (Z)-propenyl ethers derived from respective 1,3-methylidene- and 1,3-ethylidene-threitols, contrary to the corresponding erythritol derivatives, is characterized by a low stereoselectivity and a lack of stereospecificity. On the other hand, the alternative method of the oxacepham formation, based on the 4-vinyloxy-azetidinone, proceeds with an excellent stereoselectivity. The CD-spectroscopy offers an attractive tool for determination of the absolute configuration of the bridgehead carbon atom at the 5-oxacepham skeleton. Chirality 16:414,421, 2004. © 2004 Wiley-Liss, Inc. [source] Stereospecificity and stereoselectivity of flobufen metabolic profile in male rats in vitro and in vivo: Phase I of biotransformationCHIRALITY, Issue 10 2001Vladimír Wsól Abstract Flobufen (F) is the original nonsteroidal antiinflammatory drug (NSAID) containing two enantiomers. The aim of this investigation was to elucidate the biotransformation pathway of F at chiral level in phase I of biotransformation. Stereoselectivity and stereospecificity of the respective enzymes were studied in male rats in vitro (microsomal and cytosolic fractions, hepatocytes suspension) and in vivo. The rac -F, (+)-R-F and (,)-S-F were used as substrates. Amounts of F enantiomers, 4-dihydroflobufen diastereoisomers (DHF) and other metabolites (M-17203, UM) were determined with a chiral HPLC method in two chromatographic runs on R,R-ULMO and allyl-terguride bonded columns. Stereoselective biotransformation of the two enantiomers of F was observed at all tested levels and significant bidirectional chiral inversion of enantiomers of F was observed in hepatocytes. Mean enantiomeric ratios of F concentrations (S-/R-), after rac -F incubations, ranging from 1.09 in cytosolic fraction to 18.23 in hepatocytes. Stereospecificity of the respective F reductases was also observed. (2R;4S)-DHF and (2S;4S)-DHF are the principal metabolites of F in microsomes and hepatocytes. Neither DHF diastereoisomers nor M-17203 were found in cytosolic fraction. Only the nonchiral metabolite, M-17203, was found in all urine and feces samples after oral administration of F. Chirality 13:754,759, 2001. © 2001 Wiley-Liss, Inc. 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