ABSTRACT
Over the last decade there has been a growing interest in chiral chromatography, a term given to the separation of optically active compounds by chromatographic techniques. This interest has arisen largely as a result of the recognition that the majority of physiologically active substances exist in chiral form. Furthermore, the different enantiomers of a drug can exhibit widely different physiological activity in both degree and nature. For example, the hormonal activity of the two enantiomers of adrenaline differ very significantly, one being many times more active than the other. Similarly, one enantiomer of ephedrine not only has no physiological activity, but degrades the activity of the other enantiomer when also present as a mixture. A particularly sad example of the contrasting physiological effect of different enantiomers is the drug Thalidomide. This drug was originally marketed as a racemic mixture of Nphthalylglutamic acid imide. The desired pharmaceutical activity resides in the R-(+)-isomer and it was not found, until too late, that the corresponding S-enantiomer, was strongly teratogenic and its presence in the racemate caused serious fetal malformations. Largely as a result of this tragedy, the chiral purity of drugs has become a very important aspect of drug assay. Furthermore, in many countries, it is now law that if a drug can exist in different chiral structures, the relative physiological activity of the different enantiomers must be determined. It follows that the separation and identification of
enantiomers is now a very important analytical problem and chiral chromatography is the natural technique to apply to the resolution of such mixtures. Chemically, chirality can result from a chiral center such as a carbon atom with different groups attached to each bond, from structural helicity as in the case of proteins, from planar chirality as demonstrated in some substituted cyclic compounds, from axial chirality as in the spiranes and from torsional chirality as shown in substituted allenes. Furthermore, other atoms such as sulfur, nitrogen, phosphorus and boron can also exhibit chirality. Simple chirality with one chiral center can be represented as follows.
