Separation and absolute configuration of the enantiomers of a degradation product of the new inhalation anesthetic sevoflurane

Abstract

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)-beta-cyclodextrin as chiral selector was studied. With this cyclodextrin derivative diluted in the polysiloxane PS 86, an unprecedented high separation factor alpha of 4.1 (at 30 degrees C) 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)-beta-cyclodextrin is R before S.