Chiral separations enantiomers, separation

Affinity liquid chromatography and chiral separations (enantiomer separations) require similar analyte properties. The solutes may have interactions through hydrogen-bonding, ligand formation, or Coulombic forces with the surface of stationary phase materials or the sites of additives however, the selectivity is controlled by the steric effects of the structures of the analyte molecules and the recognition molecules (chiral selectors). 

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... 

CHIRAL SEPARATIONS. Chiral separations are concerned with separating molecules that can exist as nnnsuperimposyhle mirror images Examples of these types of molecules, called enantiomers or optical isomers. are illustrated in Figure I. Although chirality is often associated with compounds containing a tetrahedral carbon w ith four different substituents, other atoms, such as phosphorus or sulfur, may also be chiral. In addition,... 

The synthesis and study of chiral ionic liquids have been spurred by their potential in chiral recognition, enantiomer separation and in asymmetric synthesis [660, 661]. However, there have been relatively few single-crystal X-ray studies of single enantiomers of chiral ionic liquids. These are summarised in the following text, along with those of low-melting racemates and other relevant salts. 

The chromatographic methods are considered to be most useful for chiral separations. Enantiomers can be separated by two methods (a) indirect method that utilizes derivatizing agents and (b) direct method that uses chiral stationary phases (CSPs) or chiral mobile phase additives (CMPAs) [49-56]. 

Twenty-eight chiral compounds were separated from their enantiomers by HPLC on a teicoplanin chiral stationary phase. Figure 8-12 shows some of the structures contained in the data set. This is a very complex stationary phase and modeling of the possible interactions with the analytes is impracticable. In such a situation, learning from known examples seemed more appropriate, and the chirality code looked quite appealing for representing such data. 

Sharpless epoxidations can also be used to separate enantiomers of chiral allylic alcohols by kinetic resolution (V.S. Martin, 1981 K.B. Sharpless, 1983 B). In this procedure the epoxidation of the allylic alcohol is stopped at 50% conversion, and the desired alcohol is either enriched in the epoxide fraction or in the non-reacted allylic alcohol fraction. Examples are given in section 4.8.3. 

A few GLC stationary phases rely on chemical selectivity. The most notable are stationary phases containing chiral functional groups, which can be used for separating enantiomers. ... 

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. 

Most chiral chromatographic separations are accompHshed using chromatographic stationary phases that incorporate a chiral selector. The chiral separation mechanisms are generally thought to involve the formation of transient diastereomeric complexes between the enantiomers and the stationary phase chiral ligand. Differences in the stabiHties of these complexes account for the differences in the retention observed for the two enantiomers. Often, the use of a... 

Chiral separations present special problems for vaUdation. Typically, in the absence of spectroscopic confirmation (eg, mass spectral or infrared data), conventional separations are vaUdated by analysing "pure" samples under identical chromatographic conditions. Often, two or more chromatographic stationary phases, which are known to interact with the analyte through different retention mechanisms, are used. If the pure sample and the unknown have identical retention times under each set of conditions, the identity of the unknown is assumed to be the same as the pure sample. However, often the chiral separation that is obtained with one type of column may not be achievable with any other type of chiral stationary phase. In addition, "pure" enantiomers are generally not available. 

As in tic, another method to vaUdate a chiral separation is to collect the individual peaks and subject them to some type of optical spectroscopy, such as, circular dichroism or optical rotary dispersion. Enantiomers have mirror image spectra (eg, the negative maxima for one enantiomer corresponds to the positive maxima for the other enantiomer). One problem with this approach is that the analytes are diluted in the mobile phase. Thus, the sample must be injected several times. The individual peaks must be collected and subsequently concentrated to obtain adequate concentrations for spectral analysis. 

It is possible to obtain pure enantiomers of chiral compounds. One property of separated enantiomers is to cause the rotation of the plane of polarized light by opposite... 

Synthetic chiral adsorbents are usually prepared by tethering a chiral molecule to a silica surface. The attachment to the silica is through alkylsiloxy bonds. A study which demonstrates the technique reports the resolution of a number of aromatic compoimds on a 1- to 8-g scale. The adsorbent is a silica that has been derivatized with a chiral reagent. Specifically, hydroxyl groups on the silica surface are covalently boimd to a derivative of f -phenylglycine. A medium-pressure chromatography apparatus is used. The racemic mixture is passed through the column, and, when resolution is successful, the separated enantiomers are isolated as completely resolved fiactions. Scheme 2.5 shows some other examples of chiral stationary phases. 

The nonplanarity of allenes has an interesting stereochemical consequence. 1,3-Disubstituted allenes are chiral they are not superimposable on their minor images. Even an allene as simple as 2,3-pentadiene (CH3CH=C=CHCH3) has been obtained as separate enantiomers. 

A. Mosandl, U. Hener, U. Hagenauer-Hener and A. Kustertnann, Direct enantiomer separation of chiral y-lactones from food and beverages hy multidimensional gas chromatography , /. High Resolut. Chromatogr. 12 532-536 (1989). 

From the pioneering studies of Ito et al. [117], CCC has been mainly used for the separation and purification of natural products, where it has found a large number of applications [114, 116, 118, 119]. Moreover, the potential of this technique for preparative purposes can be also applied to chiral separations. The resolution of enantiomers can be simply envisaged by addition of a chiral selector to the stationary liquid phase. The mixture of enantiomers would come into contact with this liquid CSP, and enantiodiscrimination might be achieved. However, as yet few examples have been described in the literature. 

Although some applications for preparative-scale separations have already been reported [132] and the first commercial systems are being developed [137, 138], examples in the field of the resolution of enantiomers are still rare. The first preparative chiral separation published was performed with a CSP derived from (S -N-(3,5-dinitrobenzoyl)tyrosine covalently bonded to y-mercaptopropyl silica gel [21]. A productivity of 510 mg/h with an enantiomeric excess higher than 95% was achieved for 6 (Fig. 1-3). 

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

Enantiomeric separations have become increasingly important, especially in the pharmaceutical and agricultural industries as optical isomers often possess different biological properties. The analysis and preparation of a pure enantiomer usually involves its resolution from the antipode. Among all the chiral separation techniques, HPLC has proven to be the most convenient, reproducible and widely applicable method. Most of the HPLC methods employ a chiral selector as the chiral stationary phase (CSP). 

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