No abstract

3-Amino-5-phenyl (or 5-methyl)-1,4-benzodiazepin-2-ones, which are chiral precursors of anti-respiratory syncytial virus active agents, were resolved on three different chiral stationary phases (CSPs) based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid or (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6. Among the three CSPs, the CSP that is based on (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6 and containing residual silanol group-protecting n-octyl groups on the silica surface was found to be most effective with the use of 80% ethanol in water containing perchloric acid (10 mM) and ammonium acetate (1.0 mM) as a mobile phase. The separation factors (α) and resolutions (R(S) ) were in the range of 1.90-3.21 and 2.79-5.96, respectively. From the relationship between the analyte structure and the chromatographic resolution behavior, the chiral recognition mechanism on the CSP based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid was proposed to be different from that on the CSP based on (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6. In addition, the chromatographic resolution behavior of the most effective CSP was investigated as a function of the composition of aqueous mobile phase containing organic and acidic modifier and ammonium acetate.

Mexiletine, an effective class IB antiarrhythmic agent, and its analogs were resolved on three different crown ether-based chiral stationary phases (CSPs), one (CSP 1) of which is based on (+)-(18-crown-6)-2,3,11,12-tetracarboxylic acid and the other two (CSP 2 and CSP 3) are based on (3,3'-diphenyl-1,1'-binaphthyl)-20-crown-6. Mexiletine was resolved with a resolution (R(S)) of greater than 1.00 on CSP 1 and CSP 3 containing residual silanol group-protecting n-octyl groups on the silica surface, but with a resolution (R(S)) of less than 1.00 on CSP 2. The chromatographic behaviors for the resolution of mexiletine analogs containing a substituted phenyl group at the chiral center on the three CSPs were quite dependent on the phenoxy group of analytes. Namely, mexiletine analogs containing 2,6-dimethylphenoxy, 3,4-dimethylphenoxy, 3-methylphenoxy, 4-methylphenoxy, and a simple phenoxy group were resolved very well on the three CSPs even though the chiral recognition efficiencies vary with the CSPs. However, mexiletine analogs containing 2-methylphenoxy group were not resolved at all or only slightly resolved. Among the three CSPs, CSP 3 was found to show the highest chiral recognition efficiencies for the resolution of mexiletine and its analogs, especially in terms of resolution (R(S)).