Recognition enantioseparation

Early examples of enantioselective extractions are the resolution of a-aminoalco-hol salts, such as norephedrine, with lipophilic anions (hexafluorophosphate ion) [184-186] by partition between aqueous and lipophilic phases containing esters of tartaric acid [184-188]. Alkyl derivatives of proline and hydroxyproline with cupric ions showed chiral discrimination abilities for the resolution of neutral amino acid enantiomers in n-butanol/water systems [121, 178, 189-192]. On the other hand, chiral crown ethers are classical selectors utilized for enantioseparations, due to their interesting recognition abilities [171, 178]. However, the large number of steps often required for their synthesis [182] and, consequently, their cost as well as their limited loadability makes them not very suitable for preparative purposes. Examples of ligand-exchange [193] or anion-exchange selectors [183] able to discriminate amino acid derivatives have also been described. 

More than 100 CSPs are commercially available nowadays, which should make the separation of any pair of enantiomers feasible. However, the enantiorecognition mechanisms involved in the chiral recognition between the analytes and the CSPs are complex and therefore the selection of the appropriate CSPs, depending on the structure of the analyte, is a difficult task. A common approach to develop a new enantioseparation is the stepwise trial-and-error approach based on detailed consideration of the enantiorecognition mechanisms between the chiral selector and the analyte, or on the analyst s experience, or on the consultation of literature or databases. However, this approach is time-consuming and often unsuccessful owing to the fact that achieving enantioresolution is often purely empirical... 

A selection of the most successful CSPs, chiral particles and chiral additive techniques used for analytical and preparative enantioseparation by LC is discussed in the following sections with respect to molecular recognition and experimental application. As additional sources of background information recent books and review articles2-16, which contain numerous relevant references and examine the most important aspects of the field of liquid chromatographic enantioseparation, should be consulted. 

The previously discus.sed thermodynamically controlled molecular recognition processes are the basis for a successful enantioseparation. However, from a separation methodological point of view, also the performance of the separation system has to be considered, which in addition to the thermodynamically controlled enantioselectivity determines the peak resolution () which is a measure for the quality of a separation. 

DIRECT ENANTIOSEPARATION BY LIQUID CHROMATOGRAPHY WITH CHIRAL STATIONARY PHASES (CSPs) — CHIRAL SELECTORS AND CHIRAL RECOGNITION MECHANISMS... 

In this chapter we will focus on the moleciilcir recognition niechanisms of the diverse chiral SOs and CSPs in combination with their spectra of applicability, but also aspects concerning the separation systems as well as on issues that are of interest for practical applications. This will include a discussion of structure resolution relationships as support for the selection of certain CSPs for a given separation problem, operation modes and mobile phase composition, stability, the ability to reverse the elution order to elute each of the enantiomers as the first peak, and loadability which is of primary importance for preparative enantioseparations. 

To conclude, with this broad overview of selector chemistry in combination with molecular recognition and discrimination principles for a broad range of enantiomeric compounds and various separation technologies and methods, we have tried to guide the reader through the various fields of enantioseparation. 

Analyzing Eq. (1), one realizes that when the requirement Kk + Kg is not necessary for obtaining A/x 0. This means that in CE, a chiral recognition in the classical meaning of this definition Kk + Kg) is not always necessary for a chiral separation. This is theoretically feasible but has not been undoubtedly evidenced yet experimentally. More common is the case when ixqr = ixc,s and then Kk + Kg is the necessary requirement for enantioseparation. A combined contribution of both a stereoselective binding of the enantiomers to a chiral selector Kk Ks) and a mobility difference between the transient di-astereomeric complexes ixqr + mc,s) is also possible. 

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