Design and synthesis of novel β-cyclodextrins and their application as chiral stationary phases for gas chromatography.

Abstract

Enantiomers can be directly separated only with use of systems containing a chiral selector. Cyclodextrins (CDs) and modified cyclodextrins have been used as chiral selectors for their ability to form host-guest complexes with various analytes. The scaffold of the CD allows for assembly of functional groups with controlled geometry. CDs can be readily modified through substitution of the hydroxyl groups, giving rise to derivatives with significantly different properties, especially increased solubility and controlling the hydrophobicity of the cavity. Even though CDs can be readily modified, the syntheses can be tedious and complicated with various protecting group strategies to control the reactivity of the various alcohols. The preparation of modified cyclodextrins for use as chiral stationary phases (CSP) for gas chromatography (GC) is the focal point of this research. Our effort to identify useful new β-CD derivatives involved attempts to make bridged (annulated) derivatives, could increase the thermal stability of the derivatives, and change the length, width and polarity of the CD cavity. To date, there are no reports of annulated CD derivatives in the chemical literature. In the process of evaluating a wide range of electrophiles that could accomplish annulation, several new β-CD derivatives, i.e., per(6-O-TBS-2,3-O-cyclodimethylsilyl)- β-CD, per(6-O-TBS-2,3-O-cyclodiphenylsilyl)- β-CD, per(6-O-Pivaloyl-2,3-O-cyclodimethylsilyl)-β-CD, per(6-deoxy-2,3-O-methyl)- β-CD, and per(6-deoxy-2,3-O-allyl)- β-CD, were synthesized. Two of the new derivatives were evaluated as components of stationary phases for GC, per(6-O-TBS-2,3-Ocyclodimethylsilyl)-β-CD and per(6-deoxy-2,3-O-methyl)-β-CD. Overall, this work resulted in five new CD derivatives.