Chromatography chiral separation

S-Warfarine Chiral separation chromatography and polarimetry methods. Ahmadi et al. 2014... 

Traditionally, chiral separations have been considered among the most difficult of all separations. Conventional separation techniques, such as distillation, Hquid—Hquid extraction, or even some forms of chromatography, are usually based on differences in analyte solubiUties or vapor pressures. However, in an achiral environment, enantiomers or optical isomers have identical physical and chemical properties. The general approach, then, is to create a "chiral environment" to achieve the desired chiral separation and requires chiral analyte—chiral selector interactions with more specificity than is obtainable with conventional techniques. 

Two mechanisms for chiral separations using chiral mobile-phase additives, analogous to models developed for ion-pair chromatography, have been... 

Diamide Chiral Separations. The first chiral stationary phase for gas chromatography was reported by GH-Av and co-workers in 1966 (113) and was based on A/-trifluoroacetyl (A/-TFA) L-isoleucine lauryl ester coated on an inert packing material. It was used to resolve the tritiuoroacetylated derivatives of amino acids. Related chiral selectors used by other workers included -dodecanoyl-L-valine-/-butylamide and... 

G. Subramanian, A Practical Approach to Chiral Separations by Tiquid Chromatography, VCH, Weinheim, Germany, 1994. 

Chromatographic Method. Progress in the development of chromatographic techniques (55), especially, in high performance Hquid chromatography, or hplc, is remarkable (56). Today, chiral separations are mainly carried out by three hplc methods chiral hplc columns, achiral hplc columns together with chiral mobile phases, and derivatization with optical reagents and separation on achiral columns. All three methods are usehil but none provides universal appHcation. 

Achiral Columns Together with Chiral Mobile Phases. Ligand-exchange chromatography for chiral separation has been introduced (59), and has been appHed to the resolution of several a-amino acids. Prior derivatization is sometimes necessary. Preparative resolutions are possible, but the method is sensitive to small variations in the mobile phase and sometimes gives poor reproducibiUty. 

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... 

Figure 11.3 Typical configuration for the on-line coupling of an achiral and chiral cliro-matograpliic system by means of a switching valve. The non-enantio-resolved solute is isolated on the achiral phase and then stereochemically separated on the chiral phase. Reprinted from G. Subramanian, A Practical Approach to Chiral Separation by Liquid Chromatography, 1994, pp. 357-396, with permission from Wiley-VCH.

T. A. G. Noctor, Bioanalytical applications of enantioselective high-performance liquid cliromatography in A Practical Approach to Chiral Separations by Liquid Chromatography, Subramanian G (Ed.), VCH, Weinheim, Ch. 12, pp. 357-396 (1994). 

E. Erancotte, Chromatography as a separation tool for the preparative resolution of racemic compounds in Chiral separations, applications and technology, S. Ahuja (Ed.), American Chemical Society, Washington (1997) Chapter 10. 

B. Sellergren, Enantiomer separation using tailor-made phases prepared by molecular imprinting in A practical approach to chiral separations by liquid chromatography, G. Subramanian, VCH, Weinheim (1994) Chapter 4. 

This chapter will focus on topic 3, which is normally regarded to be chiral derivatization chromatography, but will also cover other topics that might be considered when applying derivatization techniques. The goal for the separation of the race-mates may be their analysis or their preparation. Both topics will be covered in this chapter. 

Erancotte E. (1996) Chromatography as a Separation Tool for the Preparative Resolution of Racemic Compounds, in Chiral Separations. Applications and Technology, Ahuja S. (ed.), American Chemical Society, p. 271-308. 

Preparative chromatography has been used for chiral separations for years, but examples of multi-kg separations (and hence larger ones) were rare until recently. The development of SMB techniques (both hardware and simulation software) has made major breakthroughs in this field. The ability of SMB as a development tool has allowed the pharmaceutical manufacturer to obtain kilo grams quantities of enantiopure drug substances as well benefit from the economics of large-scale production. 

The versatility of chiral stationary phases and its effecitve application in both analytical and large-scale enantioseparation has been discussed in the earlier book A Practical Approach to Chiral Separation by Liquid Chromatography" (Ed. G. Sub-ramanian, VCH 1994). This book aims to bring to the forefront the current development and sucessful application chiral separation techniques, thereby providing an insight to researchers, analytical and industrial chemists, allowing a choice of methodology from the entire spectrum of available techniques. 

The effects of pH on electrokinetic velocities in micellar electrokinetic chromatography was studied by using sodium dodecyl sulfate solutions [179]. Micellar electrokinetic capillary chromatography with a sodium dodecyl sulfate pseudostationary phase has been used to determine the partition constants for nitrophenols, thiazolylazo dyes, and metal chelate compounds [180]. A similar technique was used to separate hydroquinone and some of its ether derivatives. This analysis is suitable for the determination of hydroquinone in skin-toning creams [181]. The ingredients of antipyretic analgesic preparations have also been determined by this technique [182], The addition of sodium dodecyl sulfate improves the peak shapes and resolution in chiral separations by micellar electrokinetic chromatography [183]. 

For monographs on the use of liquid chromatography to effect resolutions, see Lough, W.J. Chiral Liquid Chromatography, Blackie and Sons London, 1989 Krstulovic, A.M. Chiral Separations by HPLC Ellis Horwood Chichester, 1989 Zief, M. Crane, L.J. Ref. 122. For a review, see Karger, B.L. Anal. Chem., 1967, 39 (8), 24A. 

When the desired hydrogen uptake had been achieved, the vessel was opened, catalyst separated by filtration, and the reaction solution analysed by chiral gas chromatography (column Cydex B, 50 m, SGE Ltd). Analysis gave conversion and enantiomeric excess Enantiomeric excess is defined as IR - SI /(R+S). 

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