Chiral phases ligand exchange

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. 

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. 

V. A. Davankov, Ligand-exchange phases in Chiral Separations by HPLC, A. M. Krstulovic, Ellis Horwood Ltd., Chichester (1989) Chapter 15. 

Ligand binding, in proteins, 20 829-830 Ligand-exchange phases, for chiral separations, 6 82-83 Ligands... 

A large number of chiral molecules have been separated with ligand-exchange chiral stationary phases. A few examples with commercially available columns are given in Table 4. 

O Naobumi, H Kitahara, R Kira. Direct separation of enantiomers by high-performance liquid chromatography on a new chiral ligand-exchange phase. J Chromatogr 592 291-296, 1992. 

C Tao, TB Huang. Resolution of DL-a-amino acids on a L-hydroxyproline chiral phase by ligand-exchange chromatography. Chin Chem Lett 6 383-384, 1995. 

Ligand Exchange-Based Chiral Stationary Phases... 

In view of the importance of chiral resolution and the efficiency of liquid chromatographic methods, attempts are made to explain the art of chiral resolution by means of liquid chromatography. This book consists of an introduction followed by Chapters 2 to 8, which discuss resolution chiral stationary phases based on polysaccharides, cyclodextrins, macrocyclic glyco-peptide antibiotics, Pirkle types, proteins, ligand exchangers, and crown ethers. The applications of other miscellaneous types of CSP are covered in Chapter 9. However, the use of chiral mobile phase additives in the separation of enantiomers is discussed in Chapter 10. 

It is well known that the chiral resolution of these CSPs occurred as a result of the exchange of ligands and enantiomers on the same metal ion. Therefore, these CSPs are suitable only for those racemates which can coordinate with the metal ion. Therefore, racemates like amino acids, amines, and hydroxy acids have been resolved successliilly by the ligand-exchange process. As mentioned earlier, either the individual chiral ligand or one complexed with a metal ion is bonded onto silica gel support. Therefore, in the case of the first type of CSP, the metal ion is used in the mobile phase no metal ion is required in the mobile phase in the latter case. 

The coated ligand-exchange CSPs have been used with the mobile phases that did not cause bleeding effects. Otherwise, the CSP may lose its chiral ligand after a few runs [12]. It is very interesting to note that the values of separation factors were very high on the coated CSPs. The values of the separation factors for proline and valine amino acids were reported at 16.4 and 6.9, respectively... 

SCHEME 1 Protocol for the development and optimization of mobile phases on ligand-exchange-based CSPs. Note Use phosphate buffer only with CSPs containing ligand metal complex as the chiral selector. 

Davankov VA, Ligand exchange phases, in Chiral Separations by HPLC, Krstulovic A (Ed.), Ellis Horwood, Chichester, p. 447 (1989). 

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