Separation enantioseparation

G. Subiamanian, ed., A Practical Approach to Chiral Separations by Liquid Chmmatofpa/ihy, VCH Publishers, Vifeinheim, 1994 S. G. AUatmarit. Chromutographic Enantioseparation Methods and Applications, Ellis Horwood, New Yoik, 1991. 

J. Dingenen, Polysaccharide phases in enantioseparations in A practical approach to chiral separations by liquid chromatography, G. Subramanian, VCH, Weinheim (1994) Chapter 6. 

A chiral separation medium is a complex system. Ideally, interactions that lead to enantioseparation are maximized while nonspecific interactions should be completely suppressed. Typically, a medium for chromatographic separations involves the solid support, the selector, and the linker connecting the two, as shown in scheme 3-1. 

Enantioseparation is typically achieved as a result of the differences in interaction energies A(AG) between each enantiomer and a selector. This difference does not need to be very large, a modest A(AG) = 0.24 kcal/mol is sufficient to achieve a separation factor a of 1.5. Another mechanism of discrimination of enantiomers involves the preferential inclusion of one into a cavity or within the helical structure of a polymer. The selectivity of a selector is most often expressed in terms of retention of both enantiomers using the separation factor a that is defined as ... 

Inspired by the separation ability of cyclic selectors such as cyclodextrins and crown ethers, Malouk s group studied the synthesis of chiral cyclophanes and their intercalation by cation exchange into a lamellar solid acid, a-zirconium phosphate aiming at the preparation of separation media based on solid inorganic-organic conjugates for simple single-plate batch enantioseparations [77-80]. 

Discrimination between the enantiomers of a racemic mixture is a complex task in analytical sciences. Because enantiomers differ only in their structural orientation, and not in their physico-chemical properties, separation can only be achieved within an environment which is unichiral. Unichiral means that a counterpart of the race-mate to be separated consists of a pure enantiomeric form, or shows at least enrichment in one isomeric form. Discrimination or separation can be performed by a wide variety of adsorption techniques, e.g. chromatography in different modes and electrophoresis. As explained above, the enantioseparation of a racemate requires a non-racemic counterpart, and this can be presented in three different ways ... 

Other examples of enantioseparations include the separation of the antihelmintic drug, prazinquatel [35], which used a 4-column SMB system composed of columns of 12.5 mm i.d. packed with CTA and with methanol as the eluent. Ikeda and Murata separated the enantiomers of (3-blockers [36]. 

Some of the initial enthusiasm surrounding chiral SFC was tempered by the fact that many of the same separations had already been achieved by LC [29]. Therefore, researchers were reluctant to add SFC to their analytical laboratories. In some instances, SFC does yield separations that can not be achieved on the same CSP in LC [30, 31]. The enantioseparation of primaquine, an antimalarial compound, on a Chiralcel OD CSP is illustrated in Fig. 12-1 [32]. This compound was not resolved on the same CSP in LC [33]. The reverse situation, where a separation obtained in LC may not be observed on the same CSP in SFC, can also occur [34]. These disparities seem to be related to differences in analyte-eluent and eluent-CSP interac-... 

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. 

Following these announcements, the first wave of publications addressing the use of SMB for the manufacture of pharmaceutical products of interest was published. The separation of a chiral hetrazepine [26], WEB 2170 6-(2-chlorophenyl)-8-9-di-hydro-l-methyl-8-[(morpholinyl)-carbonyl]-4H,7H-cyclopenta[4,5]-thieno[3,2-f][l,2,4]triazolo[4,3-a][l,4]diazepine. WEB 2170 is a chiral hetrazepine from Boehringer-Ingelheim. The enantioseparation of WEB 2170 was performed using cellulose triacetate (CTA) from Merck (Darmstadt) as the CSP and with pure methanol as eluent. 

Huang, D.S., Huang, K.L., Chen, S.P. et al. (2008) Rapid reaction-diffusion model for the enantioseparation of phenylalanine across hollow fiber supported liquid membrane. Separation Science and Technology, 43 (2), 259-272. 

Efficient methods of enantioseparation are always required to control the enantiomeric purity, or to separate the target molecule or one of its chemical precursors (obtained from conventional synthetic procedures), or for monitoring the completion of enantioselective reaction process (since the production of single enantiomer is a real difficult task). 

This review provides an overview of the literature published to date on macrocyclic antibiotics exploited for enantioselective separations in high-performance liquid chromatography (HPLC). It was not intended as a comprehensive issue on the applications of such antibiotics in sub- and supercritical fluid chromatography (SFC), thin layer chromatography (TLC), capillary electrophoresis (CE), and capillary electrochromatography (CEC). A number of structural properties of the most important macrocyclic antibiotics applied in HPLC enantioseparations are listed in Table 2.1. 

For aromatic amino and hydrazino acids and several other structurally related compounds, the influence of MeOH content in both RP and POM was investigated on a teicoplanin CSP [90]. Using a hydroorganic mobile phase, complete enantiosep-arations of a-methylamino acids were not attained. However, this type of separation was suitable for the enantiomers of dopa. Further experiments performed by the same authors in POM allowed the complete enantioseparation of a-methyl-ooPA enantiomers [91]. 

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