Isocyanates as reagents for enantiomer separation: Application to amino acids, N-methylamino acids and 3-hydroxy acids

Abstract

The formation of N-alkylureido derivatives of amino acid esters increases the selectivity of a chiral stationary phase towards the enantiomers, resulting in complete separation, even for the proline and isovaline enantiomers. In the reaction of isocyanates with N-methylamino acids, N-alkylureido/N-alkylamide derivatives are formed in one step. In a similar way, 3-hydroxy acids are converted into N-alkylcarbamate/N-alkylamide derivatives. By this procedure, the enantiomers of N-methylamino and 3-hydroxy acids were separated on chiral stationary phases for the first time. The order of elution of the enantiomers of 3-hydroxy acids was determined with optically active reference compounds, obtained by stereoselective reduction of 3-keto acid esters with yeast.