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

Abstract

A liquid chromatographic chiral stationary phase, which contains two N–CH3 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–CH3 amide connecting groups was quite successful with the separation factor (α) of 1.42 and resolution (RS) of 4.22 compared with those (α of 1.09 and RS of 1.55) on the chiral stationary phase containing two N–H amide connecting groups. In addition, the chiral stationary phase containing two N–CH3 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–CH3 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.

Liquid Chromatographic Enantioseparations Utilizing Chiral Stationary Phases Based on Crown Ethers and Cyclofructans

“…In two comparative studies, two types of CSPs based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid were examined in the chiral separation of cyclic α-amino acids, including proline, pipecolic acid, and their derivatives [ 43 ], as well as methoxyphenamine and its analogs [ 44 ]. The CSPs differed only in the methylation of amide groups of the selector; the original selector has primary amides on the linkers, while the other has secondary amide groups ( Figure 7 ).…”