The preparation of novel modified cyclodextrins and their application in enantioseparations by gas chromatography.

Abstract

Since biological processes depend on the stereospecific creation and conversion of chiral molecules, each enantiomer of a molecule can have a different biological effect. While numerous synthetic drugs are sold in racemic form for reasons of cost and convenience, in many cases one of the two enantiomers of a drug will cause undesirable and perhaps even devastating effects. Therefore, effective methods for the separation and quantification of enantiomers are of great importance. Enantiomers can be separated only with the use of systems containing an optically active chiral selector. Modified cyclodextrins (CDs) are widely used as chiral selectors by virtue of their ability to form inclusion complexes. Because of the remarkably high efficiency, and sensitivity of chiral gas chromatography (GC), chiral separations by this method represent a preferred method for enantiomer analysis. The basic property of CDs that allows them to be successful for enantiomer separations is their ability to form selective inclusion complexes with a wide variety of organic molecules. The preparation and application of modified cyclodextrins for the GC separation of enantiomers is a focal point of this research. In effort to identify useful new derivatives, modifications involving unique and separate reaction of the secondary hydroxyl groups and/or annulations bridging the secondary oxygens have been examined. Several new cyclodextrin derivatives, e.g. per(6-OTBS-2,3-O-diformyl)-β-CD, per(6-OTBS-2,3-O-cyclodimethylsilyl)-β-CD, per(6-deoxy-2,3-O-cyclodimethylsilyl)-β-CD and a mixed formyl/acetyl phase have been synthesized and evaluated as components of stationary phases for capillary GC. The efficiency of each new phase to separate enantiomers was evaluated against a 30 analyte panel to evaluate the influence of the different substituents on the selectivity. These enantioseparations were also compared to those observed on four commercially available chiral phases using the same 30 analyte panel. Overall, this work resulted in nine new CD derivatives and the discovery of a new chiral selector that is comparable in efficiency to what is currently commercially available.