Enantiomer Separation (enantiomer + separation)

Distribution by Scientific Domains


Selected Abstracts


Development of a Segmented Model for a Continuous Electrophoretic Moving Bed Enantiomer Separation

BIOTECHNOLOGY PROGRESS, Issue 6 2003
Brian M. Thome
With the recent demonstration of a continuous electrophoretic "moving bed" enantiomer separation at mg/h throughputs, interest has now turned to scaling up the process for use as a benchtop pharmaceutical production tool. To scale the method, a steady-state mathematical model was developed that predicts the process response to changes in input feed rate and counterflow or "moving bed" velocities. The vortex-stabilized apparatus used for the separation was modeled using four regions based on the different hydrodynamic flows in each section. Concentration profiles were then derived on the basis of the properties of the Piperoxan-sulfated ,-cyclodextrin system being studied. The effects of different regional flow rates on the concentration profiles were evaluated and used to predict the maximum processing rate and the hydrodynamic profiles required for a separation. Although the model was able to qualitatively predict the shapes of the concentration profiles and show where the theoretical limits of operation existed, it was not able to quantitatively match the data from actual enantiomer separations to better than 50% accuracy. This is believed to be due to the simplifying assumptions involved, namely, the neglect of electric field variations and the lack of a competitive binding isotherm in the analysis. Although the model cannot accurately predict concentrations from a separation, it provides a good theoretical framework for analyzing how the process responds to changes in counterflow rate, feed rate, and the properties of the molecules being separated. [source]


Enantiomer Separation: Fundamentals and Practical Methods

CHIRALITY, Issue 9 2006
Hassan Y. Aboul-EneinArticle first published online: 5 JUL 200
No abstract is available for this article. [source]


The stereodynamics of 1,2-dipropyldiaziridines

CHIRALITY, Issue 2 2010
Oliver Trapp
Abstract N-alkylated trans -diaziridines are an intriguing class of compounds with two stereogenic nitrogen atoms which easily interconvert. In the course of our investigations of the nature of the interconversion process via nitrogen inversion or electrocyclic ring opening ring closure, we synthesized and characterized the three constitutionally isomeric diaziridines 1,2-di- n -propyldiaziridine 1, 1-isopropyl-2- n -propyldiaziridine 2, and 1,2-diisopropyldiaziridine 3 to study the influence of the substituents on the interconversion barriers. Enantiomer separation was achieved by enantioselective gas chromatography on the chiral stationary phase Chirasil-,-Dex with high separation factors , (1-isopropyl-2- n -propyldiaziridine: 1.18; 1, 2-diisopropyldiaziridine: 1.24; 100°C 50 kPa He) for the isopropyl substituted diaziridines. These compounds showed pronounced plateau formation between 100 and 150°C, and peak coalescence at elevated temperatures. The enantiomerization barriers ,G, and activation parameters ,H, and ,S, were determined by enantioselective dynamic gas chromatography (DGC) and direct evaluation of the elution profiles using the unified equation implemented in the software DCXplorer. Interestingly, 1-isopropyl-2- n -propyldiaziridine and 1,2-diisopropyldiaziridine exhibit similar high interconversion barriers ,G, (100°C) of 128.3 ± 0.4 kJ mol,1 and 129.8 ± 0.4 kJ mol,1, respectively, which indicates that two sterically demanding substituents do not substantially increase the barrier as expected for a distinct nitrogen inversion process. Chirality, 2010. © 2009 Wiley-Liss, Inc. [source]


Chromatographic evaluation and comparison of three ,-cyclodextrin-based stationary phases by capillary liquid chromatography and pressure-assisted capillary electrochromatography

ELECTROPHORESIS, Issue 19 2008
Bo Lin
Abstract Enantiomer separations were performed on three ,-cyclodextrin-based chiral stationary phases (CSP) containing the pernaphthylcarbamoylated ,-cyclodextrin (CSP 1), peracetylated ,-cyclodextrin (CSP 2) and permethylated ,-cyclodextrin (CSP 3) as chiral selectors by capillary liquid chromatography and pressure-assisted capillary electrochromatography in this study. Triethylammonium acetate/MeOH or phosphate buffer/MeOH was used as the mobile phase. The experimental factors affecting chiral separations have been examined for each CSP, including pH of the buffers, methanol content and applied voltage. Under optimal separation conditions, a number of racemic compounds were resolved into their enantiomers on three cyclodextrin-based CSP. A comparative study on the performance of three CSP revealed the presence of carbonyl functional groups as well as aromatic rings in the cyclodextrin derivatives, enhanced the interaction between the analytes and CSP, and thus improved enantioselectivity of the CSP. [source]


Coordination behaviour and two-dimensional-network formation in poly[[,-aqua-diaqua(,5 -propane-1,3-diyldinitrilotetraacetato)dilithium(I)cobalt(II)] dihydrate]: the first example of an MII,1,3-pdta complex with a monovalent metal counter-ion

ACTA CRYSTALLOGRAPHICA SECTION C, Issue 6 2008
Urszula Rychlewska
The title compound, {[CoLi2(C11H14N2O8)(H2O)3]·2H2O}n, constitutes the first example of a salt of the [MII(1,3-pdta)]2, complex (1,3-pdta is propane-1,3-diyldinitrilotetraacetate) with a monopositive cation as counter-ion. Insertion of the Li+ cation could only be achieved through application of the ion-exchange column technique which, however, appeared unsuccessful with other alkali metals and the ammonium cation. The structure contains two tetrahedrally coordinated Li+ cations, an octahedral [Co(1,3-pdta)]2, anion and five water molecules, two of which are uncoordinated, and is built of two-dimensional layers extending parallel to the (010) lattice plane, the constituents of which are connected by the coordinate bonds. O,Hwater...O hydrogen bonds operate both within and between these layers. The crystal investigated belongs to the enantiomeric space group P21 with only one (,) of two possible optical isomers of the [Co(1,3-pdta)]2, complex. A possible cause of enantiomer separation during crystallization might be the rigidification and polarization of the [M(1,3-pdta)]2, core, resulting from direct coordination of Li+ cations to three out of four carboxylate groups constituting the 1,3-pdta ligand. The structure of (I) differs considerably from those of the other [MII(1,3-pdta)]2, complexes, in which the charge compensation is realized by means of divalent hexaaqua complex cations. This finding demonstrates a significant structure-determining role of the counter-ions. [source]


Development of a Segmented Model for a Continuous Electrophoretic Moving Bed Enantiomer Separation

BIOTECHNOLOGY PROGRESS, Issue 6 2003
Brian M. Thome
With the recent demonstration of a continuous electrophoretic "moving bed" enantiomer separation at mg/h throughputs, interest has now turned to scaling up the process for use as a benchtop pharmaceutical production tool. To scale the method, a steady-state mathematical model was developed that predicts the process response to changes in input feed rate and counterflow or "moving bed" velocities. The vortex-stabilized apparatus used for the separation was modeled using four regions based on the different hydrodynamic flows in each section. Concentration profiles were then derived on the basis of the properties of the Piperoxan-sulfated ,-cyclodextrin system being studied. The effects of different regional flow rates on the concentration profiles were evaluated and used to predict the maximum processing rate and the hydrodynamic profiles required for a separation. Although the model was able to qualitatively predict the shapes of the concentration profiles and show where the theoretical limits of operation existed, it was not able to quantitatively match the data from actual enantiomer separations to better than 50% accuracy. This is believed to be due to the simplifying assumptions involved, namely, the neglect of electric field variations and the lack of a competitive binding isotherm in the analysis. Although the model cannot accurately predict concentrations from a separation, it provides a good theoretical framework for analyzing how the process responds to changes in counterflow rate, feed rate, and the properties of the molecules being separated. [source]


Application of mixtures of tartaric acid derivatives in resolution via supercritical fluid extraction

CHIRALITY, Issue 6 2007
Ildikó Kmecz
Abstract Racemic N -methylamphetamine (rac -MA) was resolved with 2R,3R -tartaric acid (TA) and its derivatives (O,O,-dibenzoyl-(2R,3R)-tartaric acid monohydrate (DBTA) and O,O,-di- p -toluoyl-(2R,3R)-tartaric acid (DPTTA)), individually and using them in different combinations. After partial diastereomeric salt formation, the free enantiomers were extracted by supercritical fluid extraction using carbon dioxide as solvent. DBTA and DPTTA are efficient resolving agents for rac -MA, the best chiral separation being obtained at a molar ratio of 0.25 resolving agent to racemic compound for both resolving agents (eeE = 82.5% and eeE = 57.9%, respectively). Compared with the two other acids, TA is practically unsuitable for enantiomer separation (eeE < 5%). Applying a mixture of one individually active and one ineffective acid in half the equivalent molar ratio, when the acids are in 1:1 ratio in the mixture, the resolution efficiency values obtained exceeded those obtained by using the components individually. Decreasing the molar ratio of resolving agent mixture to 0.25, at which the individual resolving agents give the best chiral separation, the obtained resolution efficiency values did not differ significantly from those expected. The outcome of the resolution process depended only on the amount of the individually active resolving agents in the mixture. Chirality, 2007. © 2007 Wiley-Liss, Inc. [source]


New developments in the production and use of stereoselective antibodies

CHIRALITY, Issue S1 2005
Heike Hofstetter
Abstract This article describes the production of stereoselective antibodies using both classical immunological and modern molecular biological techniques. Stereoselective antibodies against ,-hydroxy acids were raised in rabbits and mice and compared with previously produced anti-,-amino acid antibodies. It was found that both types of antibodies combine stereoselectivity with class-specificity. Sequence analyses revealed that antibodies with opposing stereoselectivities can be formed during the affinity maturation process from a common progenitor or independently using nonhomologous binding sites. For the first time, phage display was employed to obtain stereoselective antibody fragments. The versatility of stereoselective antibodies as chiral selectors was demonstrated by applying them in several immunosensors and in chiral chromatography. A simple, membrane-based optical sensor allowed detection of enantiomeric impurities at the 1/2,000 level (99.9% ee). Silica-based antibody chiral stationary phases could be used for enantiomer separation of aliphatic amino acids in standard-sized columns, while miniaturized columns allowed interfacing with an MS-detector. Chirality 17:S9,S18, 2005. © 2004 Wiley-Liss, Inc. [source]


Chiral stationary phase covalently bound with a chiral pseudo-18-crown-6 ether for enantiomer separation of amino compounds using a normal mobile phase

CHIRALITY, Issue 3 2005
Keiji Hirose
Abstract In order to apply the excellent chiral recognition ability of chiral pseudo-18-crown-6 ethers that we developed to chiral separation, we prepared a chiral stationary phase (CSP) by immobilizing a chiral pseudo-18-crown-6-type host on 3-aminopropyl silica gel. A chiral column was prepared by the slurry-packing method in a stainless steel HPLC column. A liquid chromatography system using this CSP combined with the detection by mass spectrometry was used for enantiomer separation of amino compounds. A normal mobile phase can be used on this CSP as opposed to conventional dynamic coating-type CSPs. Enantiomers of 18 common natural amino acids were efficiently separated. The chiral separation observed for amino acid methyl esters, amino alcohols, and lipophilic amines was fair using this HPLC system. In view of the correlation between the enantiomer selectivity observed in chromatography and the complexion in solution, the chiral recognition in host,guest interactions might contribute to this enantiomer separation. Chirality 17:142,148, 2005. © 2005 Wiley-Liss, Inc. [source]


Novel cinchona carbamate selectors with complementary enantioseparation characteristics for N-acylated amino acids

CHIRALITY, Issue S1 2003
Karl Heinz Krawinkler
Abstract The synthesis and chromatographic evaluation of the enantiomer separation capabilities of covalently immobilized calix[4]arene-cinchona carbamate hybrid type receptors derived from quinine (QN) and its corresponding C9-epimer (eQN) in different solvents are reported. The receptors display complementary enantiomer separation profiles in terms of elution order, chiral substrate specificity, and mobile phase characteristics, indicating the existence of two distinct chiral recognition mechanisms. The QN-derived receptor binds the (S)-enantiomers of N-acylated amino acids more strongly, shows preferential recognition of open-chained amino acids, and superior enantioselectivity in polar media such as methanol/acetic acid. In contrast, the eQN congener preferentially recognizes the corresponding (R)-enantiomers, displays good enantioselectivity (, up to 1.74) for cyclic amino acids, and enhanced stereodiscriminating properties in apolar mobile phases, e.g., chloroform/acetic acid. A comparison of the enantiomer separation profiles with those of the corresponding QN and eQN tert -butyl carbamate congeners indicates no significant level of cooperativity between the calix[4]arene module and the cinchona units in terms of overall chiral recognition, most probably as a consequence of residual conformational flexibility of the calixarene module and the carbamate linkage. Chirality 15:S17,S29, 2003. © 2003 Wiley-Liss, Inc. [source]


Separation of propranolol enantiomers by CE using sulfated ,-CD derivatives in aqueous and non-aqueous electrolytes: Comparative CE and NMR study,

ELECTROPHORESIS, Issue 9 2010
Anne-Catherine Servais
Abstract Separations using CE employing non-aqueous BGE are already as well established as separations in aqueous buffers. The separation mechanisms in achiral CE with non-aqueous BGEs are most likely similar to those in aqueous buffers. However, for the separation of enantiomers involving their interaction with chiral buffer additives, the interaction mechanisms might be very different in aqueous and non-aqueous BGEs. While the hypothesis regarding distinct mechanisms of enantiomer separations in aqueous and non-aqueous BGEs has been mentioned in several papers, no direct proof of this hypothesis has been reported to date. In the present study, the enantiomers of propranolol were resolved using CE in aqueous and non-aqueous methanolic BGEs with two single isomer sulfated derivatives of ,-CD, namely heptakis (2,3-diacetyl-6-sulfo)-,-CD and heptakis (2,3-dimethyl-6-sulfo)-,-CD. The enantiomer migration order of propranolol was inverted when an aqueous BGE was replaced with non-aqueous BGE in the case of heptakis (2,3-dimethyl-6-sulfo)-,-CD but remained the same in the case of heptakis (2,3-diacetyl-6-sulfo)-,-CD. The possible molecular mechanisms leading to this reversal of enantiomer migration order were studied by using nuclear overhauser effect spectroscopy in both aqueous and non-aqueous BGEs. [source]


Investigation of the stereodynamics of tris-(, -diimine),transition metal complexes by enantioselective dynamic MEKC

ELECTROPHORESIS, Issue 2 2009
Sabrina Bremer
Abstract Enantiomerization of octahedral tris(, -diimine),transition metal complexes was investigated by enantioselective dynamic MEKC. Varying both the transition metal ion (Fe2+, Fe3+, and Ni2+) and the bidentate diimine ligand (1,10-phenanthroline and 2,2,-bipyridyl), the enantiomer separations were performed either in a 100,mM sodium tetraborate buffer (pH 9.3) or in a 100,mM sodium tetraborate/sodium dihydrogenphosphate buffer (pH 8.0) both containing sodium cholate as chiral surfactant. The unified equation of dynamic chromatography was employed to determine apparent reaction rate constants from the electropherograms showing distinct plateau formation. Apparent activation parameters ,H, and ,S, were calculated from temperature-dependent measurements between 10.0 and 35.0°C in 2.5,K steps. It was found that the nature of the central metal ion and the ligand strongly influence the enantiomerization barrier. Surprisingly, complexes containing the 2,2,-bipyridyl ligand show highly negative activation entropies between ,103 and ,116,J (K,mol),1 while the activation entropy of tris(1,10-phenanthroline) complexes is positive indicating a different mechanism of interconversion. Furthermore, it was found that the Ni2+ complexes are stereostable under the conditions investigated here making them a lucent target as enantioselective catalysts. [source]


1,3-Diethynylallenes: Stable Monomers, Length-Defined Oligomers, Asymmetric Synthesis, and Optical Resolution

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Issue 21 2007
Matthijs K. J. ter Wiel
Abstract A series of differently substituted 1,3-diethynylallenes (DEAs) have been synthesized, confirming that the previously introduced construction protocols tolerate a variety of functional groups. The new DEAs bear at least one polar group to facilitate enantiomer separations on chiral stationary phases and to allow further functionalization. They are thermally and environmentally stable compounds since bulky substituents next to the cumulene moiety suppress the tendency to undergo [2+2] cyclodimerization. A series of length-defined oligomers were obtained as mixtures of stereoisomers by oxidative coupling of a monomeric DEA under Glaser,Hay conditions. The electronic absorption data indicate a lack of extended ,-electron conjugation across the oligomeric backbone due to the orthogonality of the allenic ,-systems. Remarkably, even complex mixtures of stereoisomers only yield one single set of NMR signals, which underlines the low stereodifferentiation in acyclic allenoacetylenic structures. Optical resolution of DEAs represents an amazing challenge, and preliminary results on the analytical level are reported. Asymmetric synthesis by Pd-mediated SN2,-type cross-coupling of an alkyne to an optically pure bispropargylic precursor opens another promising route to optically active allenes with stereoselectivities currently reaching up to 78,% ee. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007) [source]


Recent Developments in Synthetic Chemistry, Chiral Separations, and Applications of Tröger's Base Analogues

HELVETICA CHIMICA ACTA, Issue 3 2009
Sergey Sergeyev
Abstract Tröger's base is a well-known chiral molecule with a few unusual structural features. The chemistry of Tröger's base analogues has been greatly developed over the last 20 years, and numerous interesting applications in supramolecular chemistry and in molecular recognition have emerged. This Review gives a short overview of the chemistry of Tröger's base and its analogues, with particular focus on recent achievements in synthesis, enantiomer separations, and applications. [source]


Development of a Segmented Model for a Continuous Electrophoretic Moving Bed Enantiomer Separation

BIOTECHNOLOGY PROGRESS, Issue 6 2003
Brian M. Thome
With the recent demonstration of a continuous electrophoretic "moving bed" enantiomer separation at mg/h throughputs, interest has now turned to scaling up the process for use as a benchtop pharmaceutical production tool. To scale the method, a steady-state mathematical model was developed that predicts the process response to changes in input feed rate and counterflow or "moving bed" velocities. The vortex-stabilized apparatus used for the separation was modeled using four regions based on the different hydrodynamic flows in each section. Concentration profiles were then derived on the basis of the properties of the Piperoxan-sulfated ,-cyclodextrin system being studied. The effects of different regional flow rates on the concentration profiles were evaluated and used to predict the maximum processing rate and the hydrodynamic profiles required for a separation. Although the model was able to qualitatively predict the shapes of the concentration profiles and show where the theoretical limits of operation existed, it was not able to quantitatively match the data from actual enantiomer separations to better than 50% accuracy. This is believed to be due to the simplifying assumptions involved, namely, the neglect of electric field variations and the lack of a competitive binding isotherm in the analysis. Although the model cannot accurately predict concentrations from a separation, it provides a good theoretical framework for analyzing how the process responds to changes in counterflow rate, feed rate, and the properties of the molecules being separated. [source]


Engineering functional materials by halogen bonding

JOURNAL OF POLYMER SCIENCE (IN TWO SECTIONS), Issue 1 2007
Pierangelo Metrangolo
Abstract Engineering functional materials endowed with unprecedented properties require the exploitation of new intermolecular interactions, which can determine the characteristics of the bulk materials. The great potential of Halogen Bonding (XB), namely any noncovalent interaction involving halogens as electron acceptors, in the design of new and high-value functional materials is now emerging clearly. This Highlight will give a detailed overview on the energetic and geometric features of XB, showing how some of them are quite constant in most of the formed supramolecular complexes (e.g., the angle formed by the covalent and the noncovalent bonds around the halogen atom), while some others depend strictly on the nature of the interacting partners. Then, several specific examples of halogen-bonded supramolecular architectures, whose structural aspects as well as applications in fields as diverse as enantiomers' separation, crystal engineering, liquid crystals, natural, and synthetic receptors, will be fully described. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: PolymChem 45: 1,15, 2007 [source]