Enantiomeric Resolution of Novel Aryloxyaminopropanol Derivatives with β-Adrenoceptor Antagonist Activity on a Derivatised Amylose Chiral Stationary Phase

Summary

The chromatographic retention and resolution of the enantiomers of a novel series of aryloxyaminopropanol derivatives with β-adrenoceptor antagonist activity have been investigated using a Chiralpak AD CSP. The influence of mobile phase composition, particularly alcohol modifier content and composition, on analyte retention and separation were determined; the final composition being hexane:ethanol:methanol:diethylamine (85:3.75:11.25:0.1% by volume). Analyte structure, including the position and nature of the aromatic substituents, steric bulk of the nitrogen alkyl substituent and length and bulk of the side chain were found to influence both retention and chiral discrimination. Semi-preparative isolation of the enantiomers of two of the compounds, followed by CD analysis of complexes formed on reaction with molybdenum tetraacetate, indicated that the enantiomeric elution order for both compounds was the same as that of propranolol, i.e. R- before S-.