Resolution of methoxyphenamine and its analogues on a chiral stationary phase based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid.

A liquid chromatographic chiral stationary phase, which contains two N-CH amide connecting groups, based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid was first applied to the resolution of methoxyphenamine (2-methoxy-N-methylamphetamine, a β-adrenergic receptor agonist used as a bronchodilator). The resolution of methoxyphenamine on the chiral stationary phase containing two N-CH amide connecting groups was quite successful with the separation factor (α) of 1.42 and resolution (R ) of 4.22 compared with those (α of 1.09 and R of 1.55) on the chiral stationary phase containing two N-H amide connecting groups. In addition, the chiral stationary phase containing two N-CH amide connecting groups was applied to the resolution of methoxyphenamine analogues. From the comparison of the resolution results of methoxyphenamine with those of methoxyphenamine analogues on the chiral stationary phase containing two N-CH amide connecting groups, the N-methyl group and the 2-methoxyphenyl group of methoxyphenamine were elucidated to be the structurally essential parts for the resolution on the chiral stationary phase.