Abstract

It is well known for several decades that the two enantiomeric forms of a chiral compound can have very different effects on the human body. For this reason the synthesis or extraction from a natural source of a potential new drug, as well as its marketing, require a careful control of its optical purity. Chromatographic techniques can respond extremely well to this need, both in the analytical and in the preparative field.

Among the several methods developed for this purpose, one of the first and of the most effective is the Chiral Ligand-Exchange Chromatography, which is based on the stability difference between the metallic diastereomeric complexes containing one or the other of the two enantiomers to be separated and a suitable chiral selector. This method has been effectively used for resolving racemic mixtures of products of biomedical and/or pharmacological interest, such as α - and β-amino acids either proteinogenic or non-proteinogenic, oligopeptides, amino alcohols or β-blockers. All these substances are linked together by their ability to bind metal ions, the most widely used of which is Cu(II). The chiral selector can be a component of either the mobile or the stationary phase, to which it can be either chemically bonded or dynamically adsorbed. The latter method has several advantages of convenience and, above all, cheapness. The preparation of dynamically-coated chiral stationary phases for Ligand-Exchange Chromatography has produced a large number of applications, the main of which, both in TLC and in HPLC, are reviewed below.

Keywords: Chiral chromatography, enantiomer resolution, ligand-exchange, dynamic coating, impregnating chiral agent, thin layer chromatography, high performance liquid chromatography.

Graphical Abstract