Enantioseparation of acetyltropic acid by countercurrent chromatography with sulfobutyl ether-β-cyclodextrin as chiral selector.

Abstract

Acetyltropic acid is an important synthetic intermediate for preparation of tropane alkaloid derivatives, which can be used as anticholinergic drugs, deliriants, and stimulants. In the present work, acetyltropic acid was successfully enantioseparated by countercurrent chromatography using sulfobutyl ether-β-cyclodextrin as chiral selector. A biphasic solvent system composed of n-butyl acetate/n-hexane/0.1mol/L citrate buffer at pH=2.2 containing 0.1mol/L of sulfobutyl ether-β-cyclodextrin (7:3:10, v/v) was selected, which produced a suitable distribution ratio DS =1.14, DR =2.31 and a high enantioseparation factor α=2.03. Baseline separation was achieved for preparative enantioseparation of 50mg of racemic acetyltropic acid. A method for chiral analysis of acetyltropic acid by conventional reverse phase liquid chromatography with hydroxylpropyl-β-cyclodextrin as mobile phase additive was established, and formation constants of inclusion complex were determined. It was found that different substituted β-cyclodextrin should be selected for enantioseparation of acetyltropic acid by countercurrent chromatography and reverse phase liquid chromatography.