Preparative enantioseparation of synephrine by conventional and pH-zone-refining counter-current chromatography

Abstract Synephrine, a chiral adrenergic agonist, exists as R - (more active) and S -enantiomers (less active) that are difficult to separate because of their alkalinity and high polarity. Herein, we show that although this enantioseparation can hardly be achieved by high-performance liquid chromatography, acceptable preparative separation can be realized using high-speed counter-current chromatography (HSCCC) and pH-zone-refining counter-current chromatography (CCC) under optimal conditions. Specifically, 23.0 mg of S -synephrine and 25.0 mg of R -synephrine were isolated from 60.0 mg of racemic synephrine by conventional HSCCC, while 70.0 mg of S -synephrine and 69.0 mg of R -synephrine were obtained from 200.0 mg of racemic synephrine by pH-zone-refining CCC. The pH-zone-refining CCC was identified as the most efficient enantioseparation technique for synephrine and can be applied for the preparative enantioseparation of other β-amino alcohols.