Synthesis and evaluation of 1,3,5-triazine derivatives of amino acids for enantiomeric resolution of amine drugs

Derivatizing reagents were prepared using cyanuric chloride and the amino acids phenylalanine, trans-4-hydroxy-proline, proline, valine, leucine isoleucine and the amides of alanine and phenylalanine. The enantiomers of phenylpropanolamine (;Reagents prepared with amino acids containing two chiral centers were found to provide better resolution than those with one. Specifically, the reagent obtained from trans-hydroxy-proline was found to resolve enantiomers of the test drugs better than the one obtained from proline. Similarly, the reagent from isoleucine was found to be more efficient than that obtained from leucine. Phenylpropanolamine was the best resolved drug using any of these reagents, regardless of the column or particular reagent used. The trans-hydroxy-proline-reagent may be considered the best of those evaluated, because it afforded low retention times and high resolution.;On the basis of a single experiment, it was concluded that (+)-norephedrine reacted slightly faster with the trans-hydroxy-proline-reagent than did (;Attempts to recover a pure enantiomer from its diastereomer via reductive hydrolysis or hydrogenolysis were not successful. None of the reagents tested gave promising results when tried as enantioselective precipitants.;All the five drugs used in this study could be baseline resolved into their enantiomers by at least one of the reagents synthesized in this study. Overall, these reagents have a potential of being used for the enantiospecific analysis of amine containing-chiral drugs.