Stereoselectiveseparation of racemic trans-paroxol, N-methylparoxetine and paroxetine containing two chiral carbon centres by countercurrent chromatography

Abstract

Racemic trans-paroxol, trans-N-methylparoxetine and trans-paroxetine containing two chiral centres were stereoselectively separated using countercurrent chromatography with hydroxypropyl-β-cyclodextrin as the chiral selector. A two-phase solvent system composed of n-butyl acetate and 0.1 mol L−1 sodium carbonate-sodium bicarbonate buffer at pH 9.2 (1:1, v/v) was selected, and 0.10 mol L−1 hydroxypropyl-β-cyclodextrin was added to the aqueous phase as the chiral selector. Racemic trans-N-methylparoxetine and racemic trans-paroxol (20 mg of each) were stereoselectively separated by countercurrent chromatography in an individual run, yielding 7.1–8.3 mg of enantiomers with a purity of 95–98%, where the recovery of each separated isomer reached approximately 70–83%. Racemic trans-paroxetine (20 mg) was stereoselectively separated by countercurrent chromatography using a recycling elution mode with a biphasic solvent system composed of n-hexane: n-butyl acetate: 0.1 mol L−1 sodium carbonate-sodium bicarbonate buffer at pH 9.2 (9:1:10, v/v/v), and 0.10 mol L−1 hydroxypropyl-β-cyclodextrin was added to the aqueous phase as the chiral selector, yielding 5.0–5.6 mg of enantiomer with a high purity of over 98–99%.