Enantiopure stereoisomeric homologues of glutamic acid: chemoenzymatic synthesis and assignment of their absolute configurations

The two enantiomeric pairs of bicyclic isoxazoline acidic amino acids, designed as conformationally constrained homologues of glutamic acid, have been prepared by taking advantage of a nitrile oxide cycloaddition coupled to highly selective biocatalyzed transformations. All four isomeric target amino acids were obtained with enantiomeric excesses higher than 99%. The absolute configurations were attributed to the compounds under study by comparing the experimental and theoretical vibrational circular dichroism features of two selected reaction intermediates. These absolute configurations were further confirmed using experimental and theoretical specific rotations.