Chromatography separation of enantiomers

Pirkle, W.H., Finn, J.M., Schreiner, J.L., and Hamper, B.C. (1981) A widely useful chiral stationary phase for the high-performance liquid chromatography separation of enantiomers, J. Am. Chem. Soc. 103, 3964-3966. 

Pirkle,W. H., Pochapsky,T. C. Considerations of chiral recognition relevant to the liquid chromatography separation of enantiomers, Chem. Rev., 1989, 89, 347-362. 

W. H. Pirkle, J. M. Finn, J. L. Schreiner and B. C Hamper, A Widely Useful Chiral Stationary Phase for the High-Performance Liquid Chromatography Separation of Enantiomers, J. Am. Chem. Soc., 103 (1981) 3964. 

Bhushan, R. and Gupta, D., Thin-layer chromatography separation of enantiomers of verapamil using macrocyclic antibiotic as chiral selector, Biomed. Chromatogr., 19, 474-478, 2005. 

An interesting and practical example of the use of thermodynamic analysis is to explain and predict certain features that arise in the application of chromatography to chiral separations. The separation of enantiomers is achieved by making one or both phases chirally active so that different enantiomers will interact slightly differently with the one or both phases. In practice, it is usual to make the stationary phase comprise one specific isomer so that it offers specific selectivity to one enantiomer of the chiral solute pair. The basis of the selectivity is thought to be spatial, in that one enantiomer can approach the stationary phase closer than the other. If there is no chiral selectivity in the stationary phase, both enantiomers (being chemically identical) will coelute and will provide identical log(Vr ) against 1/T curve. If, however, one... 

It is seen from equation (22) that there will, indeed, be a temperature at which the separation ratio of the two solutes will be independent of the solvent composition. The temperature is determined by the relative values of the standard free enthalpies of the two solutes between each solvent and the stationary phase, together with their standard free entropies. If the separation ratio is very large, there will be a considerable difference between the respective standard enthalpies and entropies of the two solutes. As a consequence, the temperature at which the separation ratio becomes independent of solvent composition may well be outside the practical chromatography range. However, if the solutes are similar in nature and are eluted with relatively small separation ratios (for example in the separation of enantiomers) then the standard enthalpies and entropies will be comparable, and the temperature/solvent-composition independence is likely be in a range that can be experimentally observed. 

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., Loureiro J. M., Rodrigues A. E. (1997b) Modeling, Simulation and Operation of a Simulated Moving Bed for Continuous Chromatographie Separation of l,l -bi-2-naphthol Enantiomers, J. Chromatogr. A 169 25-35. 

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. 

Figure 8.43 Separation of enantiomers using complexation chromatography. A, Separation of alkyloxiranes on a 42 m x 0.2S mm I.O. open tubular column coated with 0.06 M Mn(II) bis-3-(pentafluoro-propionyl)-IR-camphorate in OV-ioi at 40 C. B, Separation of D,L-amino acids by reversed-phase liquid chromatography using a mobile phase containing 0.005 M L-histidine methyl ester and 0.0025 M copper sulfate in an ammonium acetate buffer at pH 5.5. A stepwise gradient using increasing amounts of acetonitrile was used for this separation.

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. 

One of the most powerful methods for determining enantiomer composition is gas or liquid chromatography, as it allows direct separation of the enantiomers of a chiral substance. Early chromatographic methods required the conversion of an enantiomeric mixture to a diastereomeric mixture, followed by analysis of the mixture by either GC or HPLC. A more convenient chromatographic approach for determining enantiomer compositions involves the application of a chiral environment without derivatization of the enantiomer mixture. Such a separation may be achieved using a chiral solvent as the mobile phase, but applications are limited because the method consumes large quantities of costly chiral solvents. The direct separation of enantiomers on a chiral stationary phase has been used extensively for the determination of enantiomer composition. Materials for the chiral stationary phase are commercially available for both GC and HPLC. 

Y. Bereznitski, R. Thompson, E. O Neill and N. Grinberg, Thin-layer chromatography—a useful technique for the separation of enantiomers, J. AOAC Int., 84(4) (2001) 1242-1251. 

Ding, GS. etal.. Chiral separation of enantiomers of amino acid derivatives by high-performance liquid chromatography on a norvancomycin-bonded chiral stationary phase, Talanta, 62, 997, 2004. 

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. 

A lot of published data on the separation of enantiomers of flavors and fragrances by GC is reviewed by Chirbase/Flavor database. Table 1. summarizes the enantiomer separation of oxygenated monoterpenes on chiral stationary phases of cyclodextrin derivatives by high resolution gas chromatography. 

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

Chromatography may be used for the direct separation of enantiomers ( chiral chromatography ) and also for the normal separation of diastereomeric pairs. 

Based on preliminary results from Helfferich130, further developments by Davankov and co-workers5 131 133 turned the principle of chelation into a powerful chiral chromatographic method by the introduction of chiral-complex-forming synlhetie resins. The technique is based on the reversible chelate complex formation of the chiral selector and the selectand (analyte) molecules with transient metal cations. The technical term is chiral ligand exchange chromatography (CLEC) reliable and complete LC separation of enantiomers of free a-amino acids and other classes of chiral compounds was made as early as 1968 131. 

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