Separation of enantiomers: needs, challenges, perspectives.

Chiral drugs, agrochemicals, food additives and fragrances represent classes of compounds with high economic and scientific potential. First the present implications of their chiral nature and necessity of separating enantiomers are summarised in this article. In the following a brief overview of the actual approaches to perform enantioseparations at analytical and preparative scale is given. Challenging aspects of these strategies, such as problems associated with data management, choice of suitable chiral selectors for given enantioseparations and enhanced understanding of the underlying chiral recognition principles, are discussed. Alternatives capable of meeting the requirements of industrial processes, in terms of productivity, cost-effectiveness and environmental issues (e.g., enantioselective membranes) are critically reviewed. The impact of combinatorial methodologies on faster and more effective development and optimisation of novel chiral selectors is outlined. Finally, the merits and limitations of most recent trends in discrimination of enantiomers, including advances in the fields of sensors, microanalysis systems, chiroptical methods and chemical force microscopy are evaluated.

[1]  S. Allenmark,et al.  Proteins and peptides as chiral selectors in liquid chromatography , 1994 .

[2]  R. Rogers CDMA takes root at first meeting , 1999 .

[3]  H. Aboul‐Enein,et al.  The Impact of Stereochemistry on Drug Development and Use , 1997 .

[4]  F. Erni,et al.  Chiral recognition and enantiomeric resolution based on host-guest complexation with crown ethers in capillary zone electrophoresis , 1992 .

[5]  E. Yashima,et al.  Polysaccharide Derivatives for Chromatographic Separation of Enantiomers. , 1998, Angewandte Chemie.

[6]  E. Yashima,et al.  NMR Studies of Chiral Discrimination Relevant to the Liquid Chromatographic Enantioseparation by a Cellulose Phenylcarbamate Derivative , 1996 .

[7]  R. Bhushan,et al.  Direct enantiomeric resolution of some 2-arylpropionic acids using (-)-brucine-impregnated thin-layer chromatography. , 1999, Biomedical chromatography : BMC.

[8]  R. McKendry,et al.  Chiral discrimination by chemical force microscopy , 1998, Nature.

[9]  M. Morbidelli,et al.  Simulated moving bed chromatographic resolution of a chiral antitussive. , 1998, Journal of chromatography. A.

[10]  I. Wainer,et al.  Investigation of the enantioselective separations of α-alkylarylcarboxylic acids on an amylose tris(3,5-dimethylphenylcarbamate) chiral stationary phase using quantitative structure-enantioselective retention relationships Identification of a conformationally driven chiral recognition mechanism , 1996 .

[11]  R. Gotti,et al.  Semisynthetic chondroitins as chiral buffer additives in capillary electrophoresis. , 1999, Journal of chromatography. A.

[12]  G. P. Blanch,et al.  Rapid Recognition of Olive Oil Adulterated with Hazelnut Oil by Direct Analysis of the Enantiomeric Composition of Filbertone , 1998 .

[13]  R. Longhi,et al.  Combinatorial synthesis of highly selective cyclohexapeptides for separation of amino Acid enantiomers by capillary electrophoresis. , 1998, Analytical chemistry.

[14]  A. Dzgoev,et al.  ENANTIOSELECTIVE MOLECULARLY IMPRINTED POLYMER MEMBRANES , 1999 .

[15]  P. Stephens,et al.  Determination of absolute configuration using circular dichroism: Tröger’s Base revisited using vibrational circular dichroism , 1999 .

[16]  A. Messina,et al.  Direct resolution of optically active isomers on chiral packings containing ergoline skeleton. 6. Enantioseparation of profens. , 1999, Chirality.

[17]  W. Lindner,et al.  (S,S)-diphenylethylethanediamine derivatives as chiral selectors. II, Gasparrini-type bound chiral stationary phase with high enantioselectivity for naphthylamides , 1991 .

[18]  C. Minguillón,et al.  Carbamates of cellulose bonded on silica gel: Chiral discrimination ability as HPLC chiral stationary phases , 1998 .

[19]  Paul Richert,et al.  Applications of simulated moving-bed chromatography to the separation of the enantiomers of chiral drugs , 1997 .

[20]  Ryoji Noyori,et al.  Novel packing material for optical resolution: (+)-poly(triphenylmethyl methacrylate) coated on macroporous silica gel , 1981 .

[21]  C. Bertucci,et al.  Determination of optical purity by high-performance liquid chromatography upon non-chiral stationary phases with dual circular dichroism/absorption detection , 1994 .

[22]  E. Yashima,et al.  Computational Studies on Chiral Discrimination Mechanism of Phenylcarbamate Derivatives of Cellulose , 1999 .

[23]  W. Lindner,et al.  Enantioselective liquid-solid extraction for screening of structurally related chiral stationary phases , 2000 .

[24]  D P Glavin,et al.  Microfabricated capillary electrophoresis amino acid chirality analyzer for extraterrestrial exploration. , 1999, Analytical chemistry.

[25]  A. Tambuté,et al.  A comparison of LC and SFC for cellulose‐ and amylose‐derived chiral stationary phases , 1995 .

[26]  S. Wise,et al.  Comparison of liquid and supercritical fluid chromatography for the separation of enantiomers on chiral stationary phases. , 1997, Journal of pharmaceutical and biomedical analysis.

[27]  W. Lindner,et al.  Enantioselective anion exchangers based on cinchona alkaloid-derived carbamates: influence of C8/C9 stereochemistry on chiral recognition. , 1999, Chirality.

[28]  S. Terabe,et al.  Separation of neutral and basic enantiomers by cyclodextrin electrokinetic chromatography using anionic cyclodextrin derivatives as chiral pseudo-stationary phases , 1996 .

[29]  D. Armstrong,et al.  A covalently bonded teicoplanin chiral stationary phase for HPLC enantioseparations , 1995 .

[30]  A. Hierlemann,et al.  Chiral discrimination of inhalation anesthetics and methyl propionates by thickness shear mode resonators: new insights into the mechanisms of enantioselectivity by cyclodextrins. , 1997, Analytical chemistry.

[31]  Frances H. Arnold,et al.  Molecularly imprinted ligand-exchange adsorbents for the chiral separation of underivatized amino acids , 1997 .

[32]  S. Marchese,et al.  Enantiomeric separations of halogen-substituted 2-aryloxypropionic acids by high-performance liquid chromatography on a terguride-based chiral stationary phase , 1996 .

[33]  B. Koppenhoefer,et al.  The Determination of Small Amounts of Enantiomeric Impurities in α-Halo Carboxylic Acids , 1987 .

[34]  F. Švec,et al.  Highly selective chiral recognition on polymer supports: preparation of a combinatorial library of dihydropyrimidines and its screening for novel chiral HPLC ligands , 1998 .

[35]  Andreas Seidel-Morgenstern Optimization and comparison of different modes of preparative chromatography , 1998 .

[36]  I. Wainer,et al.  Mechanistic investigation into the enantioselective separation of mexiletine and related compounds, chromatographed on an amylose tris(3,5-dimethylphenylcarbamate) chiral stationary phase , 1996 .

[37]  K. Mori Pheromones: synthesis and bioactivity , 1997 .

[38]  Use of MDL 63 246 (Hepta-Tyr) antibiotic in capillary zone electrophoresis , 1999 .

[39]  K. Mosbach,et al.  Receptor binding mimetics: a novel molecularly imprinted polymer , 1995 .

[40]  P. Julius Zu August Bernthsens 70. Geburtstag , 1925 .

[41]  R. Suedee,et al.  Direct resolution of propranolol and bupranolol by thin‐layer chromatography using cellulose derivatives as stationary phase , 1997 .

[42]  I. Wainer Drug stereochemistry : analytical methods and pharmacology , 1993 .

[43]  Klaus Mosbach,et al.  Molecular imprinting of amino acid derivatives at low temperature (0°C) using photolytic homolysis of azobisnitriles , 1989 .

[44]  S. Fanali Identification of chiral drug isomers by capillary electrophoresis. , 1996, Journal of chromatography. A.

[45]  K. Lipkowitz Theoretical studies of brush-type chiral stationary phases , 1994 .

[46]  W. Lindner,et al.  Quinine and quinidine derivatives as chiral selectors I. Brush type chiral stationary phases for high-performance liquid chromatography based on cinchonan carbamates and their application as chiral anion exchangers , 1996 .

[47]  G. P. Blanch,et al.  Comparison of different methods for the evaluation of the authenticity of olive oil and hazelnut oil , 1998 .

[48]  H. Borén,et al.  Direct liquid chromatographic separation of enantiomers on immobilized protein stationary phases : III. Optical resolution of a series of N-aroyl d,l-amino acids by high-performance liquid chromatography on bovine serum albumin covalently bound to silica , 1983 .

[49]  J. Sandström CHIROPTICAL METHODS IN CONFORMATIONAL ANALYSIS , 1995 .

[50]  A. Krstulović Chiral separations by HPLC , 1989 .

[51]  A. Collet Resolution of Racemates: Did You Say "Classical"? , 1998, Angewandte Chemie.

[52]  W. Lindner,et al.  Diphenylethanediamine derivatives as chiral selectors. III: Comparison of four new diastereomeric chiral stationary phases prepared by addition of mono-3,5-dinitrobenzoyldiphenylethanediamine derivatives to optically pure epoxy silica , 1994 .

[53]  V. Remcho,et al.  Peer Reviewed: MIPs as Chromatographic Stationary Phases for Molecular Recognition. , 1999, Analytical chemistry.

[54]  G. Guiochon,et al.  Thermodynamic Study of an Unusual Chiral Separation. Propranolol Enantiomers on an Immobilized Cellulase , 1997 .

[55]  E. Francotte Enantioselective Chromatography: an Essential and Versatile Tool for the Analytical and Preparative Separation of Enantiomers , 1997, CHIMIA.

[56]  C. Orihuela,et al.  Chromatographic resolution of the enantiomers of a pharmaceutical intermediate from the milligram to the kilogram scale. , 1999, Journal of chromatography. A.

[57]  D. Seebach,et al.  Chromatographic resolution of synthetically useful chiral glycine derivatives by high-performance liquid chromatography , 1998 .

[58]  C. Minguillón,et al.  BENZOATES OF CELLULOSE BONDED ON SILICA GEL : CHIRAL DISCRIMINATION ABILITY AS HIGH-PERFORMANCE LIQUID CHROMATOGRAPHIC CHIRAL STATIONARY PHASES , 1997 .

[59]  M. Friedman,et al.  Chemistry, nutrition, and microbiology of D-amino acids. , 1999, Journal of agricultural and food chemistry.

[60]  M. Schmid,et al.  Chiral separation principles in capillary electrophoresis , 1997 .

[61]  W. Bowen,et al.  Preparative separation of enantiomers using hollow-fiber membrane technology , 1994 .

[62]  Kenny B. Lipkowitz,et al.  Protocol for determining enantioselective binding of chiral analytes on chiral chromatographic surfaces , 1988 .

[63]  M. Wilchek,et al.  ANTIBODIES CAN RECOGNIZE THE CHIRAL CENTER OF FREE ALPHA -AMINO ACIDS , 1998 .

[64]  V. R. Meyer Accuracy in the chromatographic determination of extreme enantiomeric ratios: A critical reflection , 1995 .

[65]  K. Tsukagoshi,et al.  Compact detection cell using optical fiber for sensitization and simplification of capillary electrophoresis–chemiluminescence detection , 1999 .

[66]  W. Lindner,et al.  Novel cinchona alkaloid carbamate C9-dimers as chiral anion-exchange type selectors for high-performance liquid chromatography. , 2000, Journal of chromatography. A.

[67]  C. Roussel,et al.  An approach to discriminating 25 commercial chiral stationary phases from structural data sets extracted from a molecular database. , 1997, Biomedical chromatography : BMC.

[68]  P. Möller,et al.  A new class of network‐polymeric chiral stationary phases , 1995 .

[69]  H. Waldmann,et al.  Cross‐Linked Enzyme Crystals (CLECs): Efficient and Stable Biocatalysts for Preparative Organic Chemistry , 1997 .

[70]  Volker Schurig,et al.  Chiral discrimination using an immunosensor , 1999, Nature Biotechnology.

[71]  V. Davankov Chiral selectors with chelating properties in liquid chromatography : fundamental reflections and selective review of recent developments , 1994 .

[72]  J. Caldwell,et al.  Regulatory aspects of the development of chiral drugs in Japan : a status report , 1991 .

[73]  G. Blaschke,et al.  Capillary electrophoresis and 1H NMR studies on chiral recognition of atropisomeric binaphthyl derivatives by cyclodextrin hosts , 1996 .

[74]  Roman Kaliszan,et al.  Quantitative structure-enationselective retention relationships for the chromatography of 1,4-benzodiazepines on a human serum albumin based HPLC chiral stationary phase: An approach to the computational prediction of retention and enantioselectivity , 1992 .

[75]  Michael Mccoy,et al.  DuPont, UNC R&D effort yields results , 1999 .

[76]  Chemiluminescence Detection in Microchip Capillary Electrophoresis , 1999 .

[77]  Davis,et al.  Carbohydrate Recognition through Noncovalent Interactions: A Challenge for Biomimetic and Supramolecular Chemistry. , 1999, Angewandte Chemie.

[78]  S. Selness,et al.  Chiral Recognition Studies: Intra- and Intermolecular 1H{1H}-Nuclear Overhauser Effects as Effective Tools in the Study of Bimolecular Complexes , 1995 .

[79]  Georges Guiochon,et al.  Preparative liquid chromatography. , 2002, Journal of chromatography. A.

[80]  C. Rosini,et al.  A spectroscopic study of the interaction of (D)- and (L)-N-(3,5-dinitrobenzoyl)valine methyl ester with n-butylamide of (S)-2-[(phenylcarbamoyl)oxy]propionic acid: direct evidence for a chromatographic chiral recognition rationale , 1990 .

[81]  Ann Thayer PHARMACEUTICALS : REDESIGNING R&D , 1998 .

[82]  D. Armstrong,et al.  Evaluation of the macrocyclic antibiotic avoparcin as a new chiral selector for HPLC. , 1998, Chirality.

[83]  E. Yashima,et al.  Enantioseparation of atropisomeric 1,1'-binaphthyl-2,2'-diyl hydrogen phosphate in capillary electrophoresis by using di- and oligosaccharides as chiral selectors: di- and oligosaccharide chiral selectors in capillary electrophoresis. , 1998, Chirality.

[84]  T. Sugo,et al.  Chiral separation of DL-tryptophan using porous membranes containing multilayered bovine serum albumin crosslinked with glutaraldehyde. , 1998, Journal of chromatography. A.

[85]  A. Mandl,et al.  Evaluation of silica gel-based brush type chiral cation exchangers with (S)-N-(3,5-dinitrobenzoyl)tyrosine as chiral selector: attempt to interpret the discouraging results , 1995 .

[86]  A. Hierlemann,et al.  Chiral discrimination using piezoelectric and optical gas sensors , 1997, Nature.

[87]  S. Ahuja Chiral separations by liquid chromatography , 1991 .

[88]  Börje Sellergren,et al.  Origin of peak asymmetry and the effect of temperature on solute retention in enantiomer separations on imprinted chiral stationary phases , 1995 .

[89]  C. Welch Evolution of chiral stationary phase design in the Pirkle laboratories , 1994 .

[90]  K. Lipkowitz,et al.  Enantioselective binding of tryptophan by .alpha.-cyclodextrin , 1992 .

[91]  Dieter Stoll,et al.  Cyclopeptide Libraries as New Chiral Selectors in Capillary Electrophoresis , 1996 .

[92]  D. J. Harrison,et al.  Micromachining a Miniaturized Capillary Electrophoresis-Based Chemical Analysis System on a Chip , 1993, Science.

[93]  F. Antia,et al.  Enantioseparation of a chiral epoxide by simulated moving bed chromatography using Chiralcel-OD , 1995 .

[94]  P. Werkhoff,et al.  Chirospecific analysis in flavor and essential oil chemistry Part A. Filbertone — the character impact compound of hazel-nuts , 1991 .

[95]  G. Blaschke,et al.  Comparative capillary electrophoretic and nuclear magnetic resonance studies of the chiral recognition of racemic metomidate with cyclodextrin hosts , 1996 .

[96]  S. Pizzarello,et al.  Enantiomeric Excesses in Meteoritic Amino Acids , 1997, Science.

[97]  Ian A. Nicholls,et al.  Receptor and transport properties of imprinted polymer membranes – a review , 1999 .

[98]  C. Rosini,et al.  Cinchona alkaloids for preparing new, easily accessible chiral stationary phases.I. 11-(10,11-Dihydro-6′-methoxy-cinchonan-9-OL)-tiopropylsilanized silica. , 1985 .

[99]  J. Caldwell Importance of stereospecific bioanalytical monitoring in drug development. , 1996, Journal of chromatography. A.

[100]  A. Foucault,et al.  Resolution of gram quantities of racemates by high-speed counter-current chromatography. , 1995, Journal of chromatography. A.

[101]  F. Gasparrini,et al.  Direct chromatographic resolution of carnitine and O-acylcarnitine enantiomers on a teicoplanin-bonded chiral stationary phase. , 1999, Journal of chromatography. A.

[102]  C. Welch,et al.  Selection of an optimized adsorbent for preparative chromatographic enantioseparation by microscale screening of a second-generation chiral stationary phase library. , 1999, Journal of combinatorial chemistry.

[103]  I. Wainer,et al.  Prediction of chiral chromatographic separations using combined multivariate regression and neural networks. , 1997, Analytical chemistry.

[104]  Edmund J Lee,et al.  Chirality Clinical Pharmacokinetic and Pharmacodynamic Considerations , 1990, Clinical pharmacokinetics.

[105]  C. R. Martin,et al.  Enantioseparation using apoenzymes immobilized in a porous polymeric membrane , 1997, Nature.

[106]  S. Fanali,et al.  Use of a Hepta‐tyr glycopeptide antibiotic as chiral selector in capillary electrophoresis , 1998, Electrophoresis.

[107]  K. Tsukagoshi,et al.  Microchip capillary electrophoresis using on-line chemiluminescence detection. , 2000, Journal of chromatography. A.

[108]  A. Rodrigues,et al.  Separation of enantiomers of a chiral epoxide by simulated moving bed chromatography , 1998 .

[109]  Toshifumi Takeuchi,et al.  Combinatorial Molecular Imprinting: An Approach to Synthetic Polymer Receptors , 1999 .

[110]  K Mosbach,et al.  Separation of amino acids, peptides and proteins on molecularly imprinted stationary phases. , 1995, Journal of chromatography. A.

[111]  Mairin Brennan From the ACS meeting , 1999 .

[112]  H. Strathmann,et al.  Stability of supported liquid membranes: State of the art , 1996 .

[113]  G. Vigh,et al.  Capillary electrophoretic separations of enantiomers using cyclodextrin‐containing background electrolytes , 1997, Electrophoresis.

[114]  Keiji Hirose,et al.  Chiral azophenolic acerands: color indicators to judge the absolute configuration of chiral amines , 1989 .

[115]  D. Armstrong,et al.  Macrocyclic Antibiotics as a New Class of Chiral Selectors for Liquid Chromatography , 1994 .

[116]  M. Jung,et al.  Analysis of the chiral aroma compound filbertone by inclusion gas chromatography , 1990 .

[117]  Y. Kubo BINAPHTHYL-APPENDED CHROMOGENIC RECEPTORS : SYNTHESIS AND APPLICATION TO THEIR COLORIMETRIC RECOGNITION OF AMINES , 1999 .

[118]  K. Mikami,et al.  Super High Throughput Screening (SHTS) of Chiral Ligands and Activators: Asymmetric Activation of Chiral Diol-Zinc Catalysts by Chiral Nitrogen Activators for the Enantioselective Addition of Diethylzinc to Aldehydes. , 1999, Angewandte Chemie.

[119]  F. Gasparrini,et al.  Chromatographic resolution of 1,2-amino alcohols on a chiral stationary phase containing N,N′-(3,5-dinitrobenzoyl)-trans-1,2-diaminocyclohexane : Theoretical and practical aspects , 1991 .

[120]  S. Han,et al.  Direct enantiomeric separations by high performance liquid chromatography using cyclodextrins. , 1997, Biomedical chromatography : BMC.

[121]  E. Yashima,et al.  Polysaccharide-Based Chiral LC Columns , 1998 .

[122]  Stephen Stinson,et al.  CUSTOM CHEMICALS: Relationships between companies that produce chemicals to special order and their clients become closer, as some 'virtual' firms contract out most activities , 1997 .

[123]  Y. Fujii,et al.  TEMPLATE SYNTHESIS OF POLYMER SCHIFF BASE COBALT(III) COMPLEX AND FORMATION OF SPECIFIC CAVITY FOR CHIRAL AMINO ACID , 1984 .

[124]  G. Blaschke,et al.  Comparative capillary electrophoresis and NMR studies of enantioseparation of dimethindene with cyclodextrins , 1998 .

[125]  E. Ariëns Stereochemistry: A source of problems in medicinal chemistry , 1986, Medicinal research reviews.

[126]  G. Guiochon,et al.  DEPENDENCE ON THE MOBILE-PHASE PH OF THE ADSORPTION BEHAVIOR OF PROPRANOLOL ENANTIOMERS ON A CELLULASE PROTEIN USED AS THE CHIRAL SELECTOR , 1999 .

[127]  K. Lipkowitz Theoretical studies of type II–V chiral stationary phases , 1995 .

[128]  Sumio Tokita,et al.  Colorimetric chiral recognition by a molecular sensor , 1996, Nature.

[129]  G. Subramanian A practical approach to chiral separations by liquid chromatography , 1994 .

[130]  N. Ogata,et al.  Enantioselective permeation of α-amino acid isomers through poly(amino acid)-derived membranes , 1990 .

[131]  Stephen Stinson,et al.  CHIRAL DRUG INTERACTIONS , 1999 .

[132]  D. Burns,et al.  Countercurrent chromatography: Apparatus, theory, and applications , 1990 .

[133]  A. Foucault,et al.  Counter-current chromatography: instrumentation, solvent selection and some recent applications to natural product purification , 1998 .

[134]  A. Margolin Novel crystalline catalysts , 1996 .

[135]  J. Haginaka,et al.  Separation and sensing based on molecular recognition using molecularly imprinted polymers. , 1999, Journal of chromatography. B, Biomedical sciences and applications.

[136]  Ton Vries,et al.  The Family Approach to the Resolution of Racemates . , 1998, Angewandte Chemie.

[137]  J. Caldwell,et al.  Stereochemical determinants of the nature and consequences of drug metabolism. , 1995, Journal of chromatography. A.

[138]  L. Sander,et al.  Chiral selectors from fruit: application of citrus pectins to enantiomer separations in capillary electrophoresis. , 1999, Journal of chromatography. A.

[139]  R. M. Izatt,et al.  ENANTIOMERIC RECOGNITION OF ARALKYL AMMONIUM SALTS BY CHIRAL PYRIDINO-18-CROWN-6 LIGANDS : USE OF CIRCULAR DICHROISM SPECTROSCOPY , 1997 .

[140]  Jean Jacques,et al.  Enantiomers, Racemates, and Resolutions , 1981 .

[141]  W. Lindner,et al.  Enantioseparation of N-protected α-amino acid derivatives by liquid-liquid extraction technique employing stereoselective ion-pair formation with a carbamoylated quinine derivative , 1997 .

[142]  G. Blaschke,et al.  Reversal of enantiomer elution order in capillary electrophoresis using charged and neutral cyclodextrins , 1996 .

[143]  J. Foley,et al.  Liquid chromatography: theory and methodology. , 1990 .

[144]  J. Vessman,et al.  Immobilized vancomycin as chiral stationary phase in packed capillary liquid chromatography , 1998 .

[145]  E. Yashima,et al.  Chiral Discrimination on Polysaccharides Derivatives , 1995 .

[146]  Lehmann,et al.  Enantiomer separation of 7-des-methyl-ormeloxifene using sulfated beta-cyclodextrin in countercurrent chromatography , 1999, Chirality.

[147]  L. Cvak,et al.  Direct resolution of optically active isomers on chiral packings containing ergoline skeletons: II. Enantioseparation of carboxylic acids , 1994 .

[148]  Klaus Mosbach,et al.  Molecular imprinting used for chiral separations , 1995 .

[149]  P. Sedmera,et al.  Direct resolution of optically active isomers on chiral packings containing ergoline skeletons. 5. Enantioseparation of amino Acid derivatives. , 1996, Analytical chemistry.

[150]  C. Minguillón,et al.  Chiral Chromatographic Discrimination Ability of a Cellulose 3,5-Dimethylphenylcarbamate/10-Undecenoate Mixed Derivative Fixed on Several Chromatographic Matrices , 1995 .

[151]  D. J. Harrison,et al.  Capillary electrophoresis and sample injection systems integrated on a planar glass chip , 1992 .

[152]  E. Francotte Achiral derivatization as a means of improving the chromatographic resolution of racemic alcohols on benzoylcellulose CSPs , 1998 .

[153]  K. Altria,et al.  A review of the current status of capillary electrochromatography technology and applications , 1997 .

[154]  W. Lindner,et al.  Chiral Anion Exchange-Type Stationary Phases Based on Cinchonan Alkaloids. An Effective Tool for the Separation of the Enantiomers of Chiral Acids , 1998 .

[155]  William H. Pirkle,et al.  Chiral molecular recognition in small bimolecular systems: a spectroscopic investigation into the nature of diastereomeric complexes , 1987 .

[156]  D. Armstrong,et al.  Derivatized vancomycin stationary phases for LC chiral separations. , 1996, Talanta.

[157]  A. Tambuté,et al.  Chiral stationary phases derived from tyrosine , 1991 .

[158]  S. Behr,et al.  Use of immobilized amyloglucosidase as chiral selector in chromatography. Immobilization and performance in liquid chromatography , 1999 .

[159]  L. Ye,et al.  Chiral recognition by molecularly imprinted polymers in aqueous media , 1998 .

[160]  Satinder Ahuja,et al.  Chiral separations : applications and technology , 1997 .

[161]  L. Sander,et al.  Enantiomer separations on chiral stationary phases in supercritical fluid chromatography , 1997 .

[162]  F. Švec,et al.  Combinatorial ‘library on bead’ approach to polymeric materials with vastly enhanced chiral recognition , 1998 .

[163]  W. Baeyens,et al.  APPLICATION OF CHIRALCEL OJ IN SUPERCRITICAL FLUID CHROMATOGRAPHY FOR THE RESOLUTION OF DIFFERENT GROUPS OF FREQUENTLY USED DRUG RACEMATES , 1997 .

[164]  H. Aboul‐Enein,et al.  Enantioselective Sensors and Biosensors in the Analysis of Chiral Drugs , 1998 .

[165]  D. Cram,et al.  Host-guest complexation. 12. Total optical resolution of amine and amino ester salts by chromatography , 1978 .

[166]  V. R. Meyer Amino Acid Racemization: A Tool for Dating? , 1991 .

[167]  William H. Pirkle,et al.  Considerations of chiral recognition relevant to the liquid chromatography separation of enantiomers , 1989 .

[168]  S. Behr,et al.  Use of immobilized amyloglucosidase as chiral selector in chromatography. Control of enantioselective retention and resolution in liquid chromatography , 1999 .

[169]  F. Erni,et al.  Chiral separations by host-guest complexation with cyclodextrin and crown ether in capillary zone electrophoresis , 1992 .

[170]  B. Sellergren,et al.  Method for synthesis and screening of large groups of molecularly imprinted polymers. , 1999, Analytical chemistry.

[171]  Thomas Pröll,et al.  Optimization strategy for simulated moving bed systems , 1998 .

[172]  L. Crane,et al.  Chromatographic chiral separations , 1988 .

[173]  C. Rosini,et al.  Cinchona alkaloids for preparing new, easily accessible chiral stationary phases , 1985 .

[174]  Alain Foucault,et al.  Donor-Acceptor Chiral Centrifugal Partition Chromatography: Complete Resolution of Two Pairs of Amino-Acid Derivatives with a Chiral II Donor Selector , 1994 .

[175]  H. Nishi Enantioselectivity in chiral capillary electrophoresis with polysaccharides. , 1997, Journal of chromatography. A.

[176]  H. Nishi Enantiomer separation of drugs by electrokinetic chromatography. , 1996, Journal of chromatography. A.

[177]  J. Blehaut,et al.  Recent aspects in simulated moving bed , 1998 .

[178]  Kenny B. Lipkowitz,et al.  Applications of Computational Chemistry to the Study of Cyclodextrins. , 1998, Chemical reviews.

[179]  V. Schurig,et al.  Direct binding of low molecular weight haptens to ELISA plates. , 1997, Journal of immunological methods.

[180]  E. Cavoy,et al.  Laboratory-developed simulated moving bed for chiral drug separations: Design of the system and separation of Tramadol enantiomers , 1997 .

[181]  J. Berridge,et al.  Screening of cyclodextrins by nuclear magnetic resonance for the design of chiral capillary electrophoresis separations , 1998 .

[182]  D. Armstrong,et al.  Highly enantioselective HPLC separations using the covalently bonded macrocyclic antibiotic, ristocetin A, chiral stationary phase. , 1998, Chirality.

[183]  V. Schurig Enantiomer analysis by complexation gas chromatography : Scope, merits and limitations , 1988 .

[184]  J. Keurentjes,et al.  Liquid membrane technology for the separation of racemic mixtures , 1996 .

[185]  S. Shinkai,et al.  Chiral discrimination of monosaccharides using a fluorescent molecular sensor , 1995, Nature.

[186]  W. Lindner,et al.  (S,S)-diphenyl-ethanediamine (DPEDA) derivatives as chiral selectors Part I. Undecenoyl bound dinitrobenzoyl-DPEDA as a broadly applicable chiral stationary phase , 1990 .

[187]  Shinji Nagamatsu,et al.  Chiral separation of a pharmaceutical intermediate by a simulated moving bed process 1 Presented at the 1998 International Symposium on Preparative Chromatography, Ion Exchange and Adsorption/Desorption Processes and Related Techniques, Washington, DC, 31 May–3 June 1998. 1 , 1999 .

[188]  C. Minguillón,et al.  Bonded cellulose-derived high-performance liquid chromatography chiral stationary phases. I. Influence of the degree of fixation on selectivity. , 1996, Journal of chromatography. A.

[189]  W. Lindner,et al.  Fourier transform infrared spectroscopic characterization of complexes of carbamoylated quinidine chiral selector and N-derivatized leucine enantiomers in solution: Evidence for stereoselective intermolecular interactions , 1999 .

[190]  David W. Guest,et al.  Evaluation of simulated moving bed chromatography for pharmaceutical process development , 1997 .

[191]  Bruce W. Pynnonen Simulated moving bed processing: escape from the high-cost box , 1998 .

[192]  E. Tesařová,et al.  Comparison of enantioselective separation of N-tert.-butyloxycarbonyl amino acids and their non-blocked analogues on teicoplanin-based chiral stationary phase , 1999 .

[193]  W. C. Still,et al.  ENANTIOSELECTIVE RESOLVING RESINS FROM A COMBINATORIAL LIBRARY. KINETIC RESOLUTION OF CYCLIC AMINO ACID DERIVATIVES , 1998 .

[194]  C. Minguillón,et al.  Chitosan derivatives as chiral selectors bonded on allyl silica gel: preparation, characterisation and study of the resulting high-performance liquid chromatography chiral stationary phases , 1999 .

[195]  Stephen Stinson,et al.  COUNTING ON CHIRAL DRUGS , 1998 .

[196]  Ronald Rogers AT 150, PFIZER SEES A HEALTHY FUTURE , 1999 .

[197]  D. Armstrong,et al.  Facile liquid chromatographic enantioresolution of native amino acids and peptides using a teicoplanin chiral stationary phase. , 1996, Journal of chromatography. A.

[198]  Jochen Strube,et al.  Design, optimization, and operation of SMB chromatography in the production of enantiomerically pure pharmaceuticals , 1999 .

[199]  H. Nishi,et al.  Enantiomeric purity determination of acetyl-L-carnitine by reversed-phase high-performance liquid chromatography using chiral derivatization. , 1999, Journal of chromatography. A.

[200]  Scott R. Wilson,et al.  X-ray Crystallographic Evidence in Support of a Proposed Chiral Recognition Mechanism. , 1996, The Journal of organic chemistry.

[201]  F. Charton,et al.  Comparison of the specific productivity of different chiral stationary phases used for simulated moving-bed chromatography , 1997 .

[202]  Christian Roussel,et al.  CHIRBASE: Database Current Status and Derived Research Applications Using Molecular Similarity, Decision Tree and 3D “Enantiophore” Search , 2001 .

[203]  W. H. Pirkle,et al.  X-Ray crystallographic support of a chiral recognition model , 1989 .

[204]  J. Kinkel,et al.  Preparative chromatographic resolution of racemates on chiral stationary phases on laboratory and production scales by closed-loop recycling chromatography , 1994 .

[205]  R. Helgeson,et al.  Host-guest complexation. 20. Chiral recognition in transport as a molecular basis for a catalytic resolving machine , 1979 .

[206]  Yang Li,et al.  Continuous beds: high-resolving, cost-effective chromatographic matrices , 1992, Nature.

[207]  G. Wulff Molecular Imprinting in Cross‐Linked Materials with the Aid of Molecular Templates— A Way towards Artificial Antibodies , 1995 .

[208]  B. Chankvetadze Capillary Electrophoresis in Chiral Analysis , 1997 .

[209]  P. Carrupt,et al.  Enantiomeric resolution of sulfoxides on a DACH-DNB chiral stationary phase: A quantitative structure-enantioselective retention relationship (QSERR) study , 1993 .

[210]  V. Davankov,et al.  Ligand exchange chromatography , 1988 .

[211]  F. Pasutto Chiral Separations by HPLC: Applications to Pharmaceutical Compounds. , 1990 .