Separation of Enantiomers by Chromatography

The success of chiral column chromatography depends on diastereoisomeric interactions between the chiral stationary phase and the enantiomers this leads to differential adsorption of enantiomers, 

Chiral stationary phases can consist of starch, which for instance 

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In contrast, CSPs have achieved great repute in the chiral separation of enantiomers by chromatography and, today, are the tools of the choice of almost all analytical, biochemical, pharmaceutical, and pharmacological institutions and industries. The most important and useful CSPs are available in the form of open and tubular columns. However, some chiral capillaries and thin layer plates are also available for use in capillary electrophoresis and thin-layer chromatography. The chiral columns and capillaries are packed with several chiral selectors such as polysaccharides, cyclodextrins, antibiotics, Pirkle type, ligand exchangers, and crown ethers. 

T. Ikai and Y. Okamoto. Structure control of polysaccharide derivatives for efficient separation of enantiomers by chromatography. Chem. Rev., 109 (2009) 6077. 

The direct separation of enantiomers by chromatography can be achieved by two fundamentally different processes The diastereoisomeric interaction can occur between the sample molecules and the stationary phase... 

For the direct separation of enantiomers by chromatography on chiral stationary phases, two strategies are essentially applicable (Fig. 6.12). The first consists in selecting the best available CSP for the racemic compound of interest, while the second consists in modifying (derivatizing) the racemic solute to accommodate it to a defined CSP until it separates on this particular CSP. 

Koppenhoefer B, Graf R, Holzschuh H, et al. (1994) CHIRBASE, a molecular database for the separation of enantiomers by chromatography. Journal of Chromatography A 666 557-563. 

Direct separation of enantiomers by chromatography Use of covalent chiral auxiliaries Stereoselective synthesis of individual enantiomers Separation of diastereoisomers by physical techniques Synthesis from chirality pool materials... 

Since the first separation of enantiomers by SMB chromatography, described in 1992 [95], the technique has been shown to be a perfect alternative for preparative chiral resolutions [10, 21, 96, 97]. Although the initial investment in the instrumentation is quite high - and often prohibitive for small companies - the savings in solvent consumption and human power, as well as the increase in productivity, result in reduced production costs [21, 94, 98]. Therefore, the technique would be specially suitable when large-scale productions (>100 g) of pure enantiomers are needed. Despite the fact that SMB can produce enantiomers at very high enantiomeric excesses, it is sometimes convenient to couple it with another separation... 

Pais L. S., Rodrigues A. E. (1998) Separation of Enantiomers by SMB Chromatography Strategies of Modeling and Proeess Performanee, Fundamentals of Adsorption 6 Proceedings of the Sixth International Conference of Fundamentals of Adsorption, E Meunier (ed.), Elsevier, Paris, p. 371-376. 

S. G. Allenmark, Separation of enantiomers by protein-based chiral phases in A practical approach to chiral separations by liquid chromatography, G. Subramanian, VCH, Weinheim (1994) Chapter 7. 

IV. SEPARATION OF ENANTIOMERS BY LIQUID CHROMATOGRAPHY ON CHIRAL STATIONARY PHASES... 

Tanaka, Y, and Terabe, S. (1995). Partial separation zone technique for the separation of enantiomers by affinity electrokinetic chromatography with proteins as chiral pseudo-stationary phases. J. Chromatogr. A 694, 277—284. 

Y Tanaka, N Matsubara, S Terabe. Separation of enantiomers by affinity electrokinetic chromatography using avidin. Electrophoresis 15 848-853, 1994. 

Biopolymers in Chiral Chromatography. Biopolymers have had a tremendous impact on the separation of nonsupernnposable. mirror-image isomers known as enantiomers. Enantiomers have identical physical and chemical properties in an achiral environment except that they rotate the plane of polarized light in opposite directions. Thus separation of enantiomers by chromatographic techniques presents special problems. Direct chiral resolution by liquid chromatography (lc) involves diastereomenc interactions between the chiral solute and the chiral stationary phase. Because biopolymers are chiral molecules and can form diastereomeric... 

Koppenhoefer, B., Nothdurft, A., Pierrot-Sanders, J., Piras, P.,Popescu, P, Roussel, C., Stiebler, M., and Trettin, U. 1993. CHIRBASE A graphical molecular database on the separation of enantiomers by liquid, supercritical fluid, and gas chromatography. Chirality 5 213-219. 

O Naobumi, H Kitahara, R Kira. Direct separation of enantiomers by high-performance liquid chromatography on a new chiral ligand-exchange phase. J Chromatogr 592 291-296, 1992. 

Even if die separation of enantiomers by any of the above methods is not completely successful, it is often possible to further raise the enantiomeric excess by crystallization or chromatography. In this way many pure enantiomers are now available. 

Gil-Av, E., Feibush, B., and Charles-Sigler, R. (1966) Separation of enantiomers by gas liquid chromatography with an optically active stationary phase. Tetrahedr. Lett. 1009-1015. 

Schurig, V. (2001) Separation of enantiomers by gas chromatography - Review. J. Chroma-togr. A 906, 275-299. 

Lindner, K. and Mannschreck, A., Separation of enantiomers by high-performance liquid chromatography on triacetylcellulose, J. Chromatogr., 193, 308, 1980. 

There are three commonly used approaches to the separation of enantiomers by HPLC. Of these, two are based on operation with conventional reversed-phase column materials.72 One approach is to derivatize the sample prior to chromatography, leading to formation of diastereomeric products of the two enantiomers that can be separated by conventional HPLC,73,74 whereas the other uses chiral selectors in the mobile phase.75 76 The third approach involves the use of chiral stationary phases. 

W. Lindner, Indirect separation of enantiomers by hquid chromatography, in M. Zief and L. J. Crane (eds.), Chromatographic Chiral Separation, Marcel Dekker, New York, 1988, pp. 91-130. 

B. Eeibush, Separation of enantiomers by asymmetric phases in gas liquid chromatography, Ph.D thesis, 1967, The Weizmann Institute of Science, Rehovot, Israel. 

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