Enantioselective liquid

Another possibility of constructing a chiral membrane system is to prepare a solution of the chiral selector which is retained between two porous membranes, acting as an enantioselective liquid carrier for the transport of one of the enantiomers from the feed solution of the racemate to the receiving side (Fig. 1-5). This system is often referred to as membrane-assisted separation. The selector should not be soluble in the solvent used for the elution of the enantiomers, whose transport is driven by a gradient in concentration or pH between the feed and receiving phases. As a drawback common to all these systems, it should be mentioned that the transport of one enantiomer usually decreases when the enantiomer ratio in the permeate diminishes. Nevertheless, this can be overcome by designing a system where two opposite selectors are used to transport the two enantiomers of a racemic solution simultaneously, as it was already applied in W-tube experiments [171]. 

Armstrong and Jin [15] reported the separation of several hydrophobic isomers (including (l-ferrocenylethyl)thiophenol, 1 -benzylnornicotine, mephenytoin and disopyramide) by cyclodextrins as chiral selectors. A wide variety of crown ethers have been synthesized for application in enantioselective liquid membrane separation, such as binaphthyl-, biphenanthryl-, helicene-, tetrahydrofuran and cyclohex-anediol-based crown ethers [16-20]. Brice and Pirkle [7] give a comprehensive overview of the characteristics and performance of the various crown ethers used as chiral selectors in liquid membrane separation. 

In general, high selectivities can be obtained in liquid membrane systems. However, one disadvantage of this technique is that the enantiomer ratio in the permeate decreases rapidly when the feed stream is depleted in one enantiomer. Racemization of the feed would be an approach to tackle this problem or, alternatively, using a system containing the two opposite selectors, so that the feed stream remains virtually racemic [21]. Another potential drawback of supported enantioselective liquid membranes is the application on an industrial scale. Often a complex multistage process is required in order to achieve the desired purity of the product. This leads to a relatively complicated flow scheme and expensive process equipment for large-scale separations. 

Selenurane oxides are also one of the hypervalent selenium compounds. Recently, the enantiomers of chiral selenurane oxide 38 were isolated for the first time by enantioselective liquid chromatography of the racemate or by spontaneous resolution occurring during slow evaporation of its acetonitrile solution or slow crystallization from the same solvent.57 The absolute configurations of the enantiomers were determined by X-ray crystallographic analysis (Scheme 17). 

In simple experiments, particulate silica-supported CSPs having various cin-chonan carbamate selectors immobilized to the surface were employed in an enantioselective liquid-solid batch extraction process for the enantioselective enrichment of the weak binding enantiomer of amino acid derivatives in the liquid phase (methanol-0.1M ammonium acetate buffer pH 6) and the stronger binding enantiomer in the solid phase [64]. For example, when a CSP with the 6>-9-(tcrt-butylcarbamoyl)-6 -neopentoxy-cinchonidine selector was employed at an about 10-fold molar excess as related to the DNB-Leu selectand which was dissolved as a racemate in the liquid phase specified earlier, an enantiomeric excess of 89% could be measured in the supernatant after a single extraction step (i.e., a single equilibration step). This corresponds to an enantioselectivity factor of 17.7 (a-value in HPLC amounted to 31.7). Such a batch extraction method could serve as enrichment technique in hybrid processes such as in combination with, for example, crystallization. In the presented study, it was however used for screening of the enantiomer separation power of a series of CSPs. 

Badaloni, E. et al., Enantioselective liquid chromatographic-electrospray mass spectrometric assay of fS-adrenergic blockers application to a pharmacokinetic smdy of sotalol in human plasma, J. Chromatogr. B, 796, 45, 2003. 

Levin, S., Abu-Lafi, S., The Role of Enantioselective Liquid Chromatography Separations Using Chiral Stationary Phases in Pharmaceutical Analysis, In Advances in Chromatography, Grushka, E. and Brown, P. R., Eds., Vol. 33, Marcel Dekker, New York, pp. 233-266, 1993. 

Rosas, M.E., K.L. Preston, D.H. Epstein, E.T. Moolchan, et al., Quantitative determination of the enantiomers of methadone and its metabolite (EDDP) in human saliva by enantioselective liquid chromatography with mass spectrometric detection, J. Chromatogr. B Anal. Technol. Biomed. Life Sci., 796(2), 355-370, 2003. 

Levin, S. and Abu-Lafi, S. The Role of Enantioselective Liquid Chromatographic Separations Using Chiral Stationary Phases in Pharmaceutical Analysis , in Advances in Chromatography. 

Vecchione, G., Casetta, B., Tomaiuolo, M., Grandone, E., Margaglione, M. A rapid method for the quantification of the enantiomers of Warfarin, Phenprocoumon and Acenocoumarol by two-dimensional-enantioselective liquid chromatography/electrospray tandem mass spectrometry. J. Chromatogr. B 850, 507-514 (2007)... 

R. Bakhtiar, L. Ramos, and F. L. S. Tse, Use of atmospheric pressure ionization mass spectrometry in enantioselective liquid chromatography. Chirality 13 (2001), 63-74 and references cited therein. 

OTHER ENANTIOSELECTIVE LIQUID-PHASE SEPARATION TECHNIQUES... 

Various techniques used in the investigations include enantioselective liquid chromatography, enantioselective H-NMR spectroscopy, polarimetry, and circular dichroism spectroscopy. This work offers a fundamental new outlook on transition states and on the relationship between the structures of photochromic compounds and the corresponding energy barriers of their ring-opening reactions. 

Preparative Enrichment of Enantiomers by Enantioselective Liquid Chromatography... 

Preparative enrichment of enantiomers should be followed by determination of their chemical and enantiomeric purities, e.g., by enantioselective liquid chromatography.25,26 In addition to the sorbents mentioned above, others may be used which are available in only smaller amounts. In our laboratory, this is true for (+)-poly(trityl methacrylate) on silica,35 which can be used for analytical purposes. Preparative separations on a column 0.5 cm in diameter, however, would require many injections of small amounts of racemate. In the case of a baseline chromatogram like that in Figure 2, the determination of enantiomeric purity by measurement of the two peak areas of the enantiomers is straightforward. An analytical chromatogram showing some separation by photometric detection in spite of peak overlap (Figure 4) can still be used for optical purity determina-tion. The simultaneous use of both photometric and chiroptical detection as... 

A. Mannschreck, On-line measurement of circular dichroism spectra during enantioselective liquid chromatography, Trends Anal. Chem. 12, 220-225 (1993) Chem. Abstr. 119, 194725 (1993). 

The brush-type of CSP was introduced by Pirkle who was one of the pioneers of modern enantioselective liquid chromatography [55]. The most frequently used 7i-acceptor phases are derived from the amino acids phenylglycine (DNBPG) (Fig. 6.8) or leucine (DNBLeu) covalently or ionically bonded to 3-aminopropyl silica gel [56, 57]. These CSPs are commercially available for analytical or preparative separation of enantiomers. Further CSPs based on amino acid or amine chiral selectors such as valine, phenylalanine, tyrosine [58] and l,2-tr s-diaminocyclohexane (DACH-DNB phase) [59] and 1,2-traus-diphenylethylene diamine (ULMO phase) [60] were also developed (Fig. 6.8). These CSPs have been applied for the preparative separation of the enantiomers of a few racemic compounds, but the number of reported preparative applications has remained very limited over the last 10 years. 

E. Erancotte, Enantioselective Liquid Chromatography A Mature Separation Technology , Lecture presented at the 14 International Symposium on Chirality ISCD 14, 2003, Hamburg (Germany). 

Mills, M.H. Mather, L.E. Gu, X.S. Hueuig, J.L. Determination of ketorolac enantiomers in plasma using enantioselective liquid chromatography on an ai-acid glycoprotein chiral stationary phase and ultraviolet detection. J.Chromatogr.B, 1994, 658, 177-182... 

Jones, D.J. Bjorksten, A.R. Detection of ketorolac enantiomers in human plasma using enantioselective liquid chromatography. J.Chromatogr.B, 1994, 661, 165-167 [plasma chiral LOD 5ng/mL naproxen... 

Lankford, S.M. Bai, S.A. Determination of the stereochemical composition of the major metabolites of verapamil in dog urine with enantioselective liquid chromatographic techniques. J.Chromatogr.B, 1995, 663, 91-101... 

Lammerhofer, M. (2010) Chiral recognition by enantioselective liquid chromatography mechanisms and modern chiral stationary phases. Review article./. Chromatogr. A, 1217, 814—856. 

Campanero, M.A. Lopez Ocariz, A. Garcia Quetglas, E. Sadaba, B. Azanza, J.R. Determination of ketorolac enantiomers in plasma using enantioselective liquid chromatography. Application to pharmacokinetic studies. Chromatographia 1998, 48 (3 ), 203-208. 

Czerwenka, C, Maier, N.M., Lindner, W. (2004) Enantiomer discrimination by mass spectrometry non-covalent interactions of an N-derivatized dipeptide with various cinchona alkaloid derivatives and comparison with enantioselective liquid-phase separations. Anal. Bioanal. Chem., 379,1039-1044. 

ENANTIOSELECTIVE LIQUID CHROMATOGRAPHIC ANALYSIS OF AMINO ACIDS... 

Schuur B, Verkuijl BJV, Minnaard AJ, de Vries JG, Heeres HJ, Feringa BL. Chiral separation by enantioselective liquid-liquid extraction. Org. Biomol. Chem. 2011 9 36-51. 

Schuur B, Winkelmam JGM, Heeres HJ. Equilibrium studies on enantioselective liquid-liquid amino acid extraction using a cinchona alkaloid extractant. Ind. Eng. Chem. Res. 2008 47 10027-10033. 

Other uses. Phopshoric add derivatives have also been used in other applications than catalytic activity. Feringa et al. have studied the enantioselective liquid-liquid extraction of (5)-phenylglycinol (396a) from the aqueous racemic mixture (396), using the bisnaphthyl phosphoric acid (348) extractant in dichloromethane phase, followed by a back extraction to... 

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