Separation and Absolute Configuration of the Enantiomers of a Degradation Product of the New Inhalation Anesthetic Sevoflurane

摘要

In a rebreathing anesthesia circuit, the inhaled anesthetic sevoflurane degrades into at least two products, termed "compound A" and "compound B." The enantiomer separation of the chiral compound B (1,1,1,3,3-pentafluoro-2-(fluoromethoxy)-3-methoxypropane) by capillary gas chromatography (cGC) using heptakis(2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-β-cyclodextrin as chiral selector was studied. With this cyclodextrin derivative diluted in the polysiloxane PS 86, an unprecedented high separation factor α of 4.1 (at 30℃) was found. Consequently, the enantiomers of compound B were isolated by preparative GC and their specific rotations were measured. In addition, their absolute configurations were determined by X-ray crystallography. To collect the X-ray data, single crystals of both enantiomers were grown in situ on the diffractometer. The levorotatory enantiomer B(-) has the R-configuration while the dextrorotatory enantiomer B(+) has the S-configuration. The elution order of the compound B enantiomers on heptakis(2,3-di-O-acetyl-6-O-tert-butyldimethylsilyl)-β-cyclodextrin is R before S.