Separation of enantiomers of N-protected non-protein amino acid esters by chiral high-performance liquid chromatography

The high-performance liquid chromatographic separation of enantiomers of N-protected nonprotein amino acid esters was investigated by using a cellulose tris(3,5-dimethylphenylcarbamate) chiral stationary phase column (Daicel Chiracel OD). The effect of the N-protecting groups and the ester groups on chiral discrimination was examined. The benzyloxycarbonyl (Z), 4-metboxybenzyloxycorbonyl, and 9-fluorenylmethoxycarbonyl derivatives gave good enantiomeric separations, while the formyl and t-butoxycarbonyl groups marred them. Almost all the alkyl esters examined and the benzyl ester gave enantiomeric separations better than or of the same order as the methyl ester. The N-Z-protected methyl esters of a number of nonprotein g-amino acids were well resolved using hexane-2-propanol as a mobile phase. The resolution of beta-amino acid derivatives was inferior to that of the isomeric alpha-amino acid derivatives.