substances suddenly increased, particularly in chiral drugs, and this interest proliferated very rapidly. This new enthusiasm was fostered by the recognition that the respective physiological activity of the isomers of a drug could differ radically and this was found to be true for many physiologically active compounds and, in particular, physiologically active biotechnology products. However, the major impetus arose from the unfortunate birth defects initiated by one of the enantiomers of Thalidomide. This drug was manufactured and sold as a racemic mixture of N-phthalylglutamic acid imide. However, the desired physiologically activity was found to reside solely in the R-(+)-isomer and it was discovered, too late, that the corresponding S-(-)-enantiomer was teratogenic and could cause serious fetal malformations. The thalidomide disaster evoked the interest of all pharmaceutical manufacturers and also the drug regulatory committees. As a result, research activity in the field of

The separation of the enantiomers of chiral drugs has become exceedingly important over recent years. This new enthusiasm was fostered by the discovery that the respective physiological activity of the isomers of a drug could differ radically and this was found to be true for many physiologically active compounds and, in particular, physiologically active biotechnology products. However, the major stimulation arose from the unfortunate birth defects initiated by one of the enantiomers of Thalidomide. This drug was manufactured and sold as a racemic mixture of N-phthalylglutamic acid imide. However, the desired physiologically activity was found to reside solely in the R-(+)-isomer and it was discovered, too late, that the correspondingS-(-)-enantiomerwasteratogenicandcaused serious fetal malformations.   Courtesy of ASTEC Inc.   Figure 36. A Commercially Available Preparative Column for the Separation of Enantiomeric Pairs

Chiral Stationary Phases Modern organic chemistry and pharmaceutical research are becoming increasingly interested in methods of asymmetric syntheses. This enthusiasm has been provoked by the differing physiological activity that has been shown to exist between the geometric isomers of pharmaceutically active compounds. A tragic example being the drug Thalidomide, which was made available as a racemic mixture of N-phthalylglutamic acid imide. The important physiological activity resides in the R-(+)-isomer and it was not found, until too late, that the S-enantiomer was probably tetratogenic and caused serious fetal malformations. The separation and identification of isomers can, clearly, be very important and chromatography can be very effective in the resolution of such mixtures. The use of GC for the separation of asymmetric isomers