Liquid Chromatographic Separation of Enantiomers

The heart of any enantioseparation by liquid chromatography is a chiral column packed with a CSP or rarely a chiral selector immobilized on the wall of a capillary. A CSP consists of a chiral selector and an inert carrier. Both constituents are equally important for the separation performance. The chromatographic literature reports several himdreds of chiral compoimds applied as chiral LC selectors. A more or less complete overview of all materials applied as chiral selectors is impossible within the framework of this short chapter. In principle, any chiral compound possessing the ability to interact noncovalently with chiral molecules has the potential to be used as chiral selector in liquid chromatography. A chiral selector has to meet a set of characteristics that depend on the goal of the separation as well as the mode and technique used. The advantages and bottlenecks of the major classes of commercially available CSPs are summarized in Table 4.1. 

CSP Coverage of analytes Compatibility with different separation modes Suitability for preparative-scale separations 

Note 3 = very good 2 = good 1 = less useful 0 = not suitable. 

Together with a chiral selector, an innert carrier contributes significantly to the performance of a CSP. Although all commercially available chiral columns currently are prepared based on totally porous particulate silica, other organic [15,35—37] and inorganic materials [38], as well monolithic [35,39—41] and core-shell silica [42] materials have been examined as a carrier for a chiral selector [39] and as capillary columns 

FIGURE 4.1 Fast separation of enantiomers of 2,2,2-trifluoro-l-(9-anthryl)ethanol on a monolithic silica column modified by coating with 6.6% (w/w) of cellulose tris(3,5- 

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Elargitai, T., Kaida, Y., and Okamoto, Y., Preparation and chromatographic evaluation of 3,5-dimethylphenyl carbamoylated beta-cyclodextrin stationary phases for normal-phase high-performance liquid-chromatographic separation of enantiomers, J. Chromatogr., 628, 11, 1993. 

Peter, A., Torok, G., and Armstrong, D.W., High-performance liquid chromatographic separation of enantiomers of unusual amino acids on a teicoplanin chiral stationary phase, J. Chromatogr. A, 793, 283, 1998. 

The evolution of CDs as chiral selectors in the liquid chromatographic separation of enantiomers has been a subject of interest for the last two decades. The presence of the chiral hollow basket, or cavity, makes these molecules suitable for the chiral resolution of a wide range of racemic compounds. At present, the use of CDs as chiral selectors for enantiomeric resolution by liquid... 

Pirkle WH, Finn JM, Hamper BC, Schreiner J, Pribish JR, A useful and conveniently accessible chiral stationary phase for liquid chromatographic separations of enantiomers, in Asymmetric Reactions and Process in Chemistry, Eliels EL, Otsuka S (Eds.), ACS Symposium Series No. 185, American Chemical Society, Washington DC, p. 245 (1982). 

Persson and Andersson [65] reviewed the unusual effects in liquid chromatographic separations of enantiomers on chiral stationary phases with emphasis on polysaccharide phases. On protein phases and Pirkle phases, reversal of the elution order between enantiomers due to... 

Pirkle, W.H. and Pochapsky, T.C. (1989) Considerations of chiral recognition relevant to the liquid chromatographic separation of enantiomers, Chem. Rev. 89, 347-362. 

Tachibana, K. and Ohnishi, A. (2001) Reversed-phase liquid chromatographic separation of enantiomers on polysaccharide type chiral stationary phases, J. Chromatogr. A 906, 127-154. 

Armstrong, D.W., Chiral stationary phases for high performance liquid chromatographic separation of enantiomers a mini-review,./. Liq. Chromatogr., 7, 353, 1984. 

W. H. Pirkle, M. H. Hyun, A. Tsiporas, B. C. Hamper, and B. Banks, A rational approach to the design of highly effective chiral stationary phases for the liquid chromatographic separation of enantiomers, J. Pharm. Biomed. Anal., 2 173 (1984). 

S. Allenmark, B. Bomgren, and H. Boren, Direct liquid chromatographic separation of enantiomers on immobilized protein stationary phases III. Optical resolution of a series of A-aroyl d, 1-amino acids by high-performance liquid chromatography onbovine serum albumin covalently bound to silica, /. Chromatogr. 264 (1983), 63-68. 

A. M. Rizzi, Band broadening in high-performance liquid chromatographic separations of enantiomers with swollen microcystalline cellulose triacetate packings. 

Allenmark, S. Bomgren, B. Boren, H. Direct liquid chromatographic separation of enantiomers on immobilized protein stationary phases. IV. Molecular interaction forces and retention behaviour in chromatography on bovine serum albumin as a stationary phase. J. Chromatogr. 1984, 316 (12), 617-624. 

A Useful and Conveniently Accessible Chiral Stationary Phase for the Liquid Chromatographic Separation of Enantiomers... 

Audebert,R. J. Liq. Chromatogr., Special Issues on Liquid Chromatographic Separation of Enantiomers, Diastereomers, and Configurational Isomers, Marcel Dekker, New York 1979 2, 1063. 

A. Peter, G. Torok and D. W. Armstrong, High-performance Liquid Chromatographic Separation of Enantiomers of Unusual Amino Acids on a Teicoplanin Chiral Stationary Phase, J. Chromatogr. A, 793 (1998)283. 

D.W. Armstrong, W. DeMond, A. Alak, W.L. Hinze, T.E. Riehl and T. Ward, Liquid Chromatographic Separation of Enantiomers Using a Chiral P-Cyclodextrin-Bonded Stationary Phase and Conventional Aqueous-Organic Mobile Phases, Anal. Chem., 57(1985)237. 

D.W. Armstrong, A M. Stalcup, M.L. Hilton, J.D. Duncan, J.R. Faulkner and S.C. Chang, Derivatized Cyclodextrins for Normal-Phase Liquid Chromatographic Separation of Enantiomers, Anal. Chem., 62(1990)1610. 

D.W. Armstrong, C D. Chang and S.H. Lee, (R)- and (S)-Naphthylethyl-carbamate-Substituted P-cyclodextrin Bonded Stationary Phases for the Reversed-Phase Liquid Chromatographic Separation of Enantiomers, J. Chromatogr., 539(1991)83. 

Hinze WI, Riehl TE, Armstrong DW, DeMond W, Alak A, Ward T. Liquid chromatographic separation of enantiomers using a chiral P-cyclodextrin-bonded stationary phase and conventional aqueous-organic mobile phases. Anal Chem 1985 57 237—42. 

Armstrong DW, Stalcup AM, Hilton ML, Duncan JD, Faulkner JR, Chang SC (1990) Derivatized cyclodextrins for normal-phase liquid chromatographic separation of enantiomers. Anal Chem 62 1610-1615... 

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