Chiral Separation by Ligand Exchange

Organic Chemist s Desk Reference, Second Edition 

From supramolecular chemistry toward constitutional dynamic chemistry and adaptive chemistry. Chem. Soc. Rev. 36 (2007) 151. 

Grinberg. Chiral separation in pharmaceutical industry. Am. Pharm. Rev. 9 (2006) 65. 

Feibush. Chiral separation via selector/selectand hydrogen bonding. Chirality 10 (1998) 382. 

Grinberg, T. Burokowski, and A. M. Stalcup. HPLCfor pharmaceutical scientists, ed. Y. Cazakevich and R. Lobrutto. Hoboken, NJ John Wiley Sons, 2007. 

---

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

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

Marchelli R, Corradini R, Galavema G et al (2006) Enantioselective separation of amino acids and hydroxy acids by ligand exchange with copptafll) cmnplexes in HPLC (chiral eluent) and fast sensing systems. In Subramanian G (ed) Chiral separation techniques. Wiley-VCH, Weinheim... 

Figure 3.2 The separation of (R)- and (5)-amino acid enantiomers by ligand exchange chromatography using proline and copper (II) sulphate solution as the chiral...

Davankov VA. Ligand-exchange phases. In Krstulovic AM, editor. Chiral separations by HPLC. New York Ellis Horwood Limited 1989. p. 175—93. 

The first successful separation using ligand exchange, via the technique of impregnation, on TLC was reported for enantiomers of amino acids by Gunther et al. [2-4] the commercial RP-18 silica gel plates were first immersed in a 0.25% copper (II) acetate solution prepared in methanol/water (1 9), dried and then immersed for 1 min in a 0.8% methanolic solution of the chiral selector (25,4R,2 / 5)-4-hydroxy-l-(2 -hydroxydodecyl)-proline. The impregnated plate, thus prepared, provided resolution of a number of enantiomeric amino acids, including substituted ones, when developed in methanol/water/acetonitrile (1 1 4 or 5 5 3). 

Chiral ligand-exchange chromatography (CLEC) ° separates enantiomers by the formation of diastereomeric metal complexes. In a first instance the technique was mainly used for the separation of amino acids. Impressive results of the first separations gave rise to intensive investigation in the field and numerous publications appeared in the literature, which have been reviewed. 

---