Chiral interactions of the fluoroether anesthetics desflurane, isoflurane, enflurane, and analogues with modified cyclodextrins studied by capillary gas chromatography and nuclear magnetic resonance spectroscopy: A simple method for column-suitability screening

Eighteen chiral analogues of the chiral fluoroether anesthetics desflurane, isoflurane, and enflurane are synthesized and studied by capillary GC on four cyclodextrin-derived stationary phases. Trends in separability and elution order of enantiomers are related to structure and absolute configuration. In particular,a very large separation factor is found for the commercial anesthetic desflurane using Lipodex(R) E stationary phase, suggesting that a preparative enantiomer separation is possible. One of the stationary phases, Cyclodex(R) G-TA, is found to be a chiral shift reagent for several of the fluoroethers. A rough correspondence is found relating the enantiomeric separation factor of a fluoroether and the chemical shift differences between its H-1 and F-19 nuclei in the NMR spectrum. Based on this data, it is proposed that a simple NMR experiment can screen chiral stationary phases prior to a desired gas chromatographic enantiomer separation of a given chiral compound.