Structural studies and NMDA activity of an enantiopure dihydroisoxazole derivative

The enantiopure 5-(2-amino-2-carboxyethyl)-4,5-dihydroisoxazole-3-carboxylic acid (−)-1b and its racemic tert-butoxycarbonylamino (Boc) precursor (±)-11 were structurally characterized by the single crystal X-ray diffraction technique. The geometrical features and the intermolecular interaction of the pure (3S,5S)-aminoacid are compared with the racemic derivative. This analysis has shown a different conformation of the dihydroisoxazole ring: (±)-11 adopts an envelope shape, while in (−)-1b it is almost planar. The intermolecular assembly is characterized by hydrogen bonds of an NH⋯O type in (±)-11 with the formation of polymeric chains, whereas in (−)-1b the hydrogen bonds determine a three dimensional network. The tight intermolecular interactions of (−)-1b could be responsible for the short distances between ionizable groups, which are important as pharmacophoric parameters for NMDA activity.

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5-(2-Amino-2-carboxylethyl)-4,5-dihydro-isoxazole-3-carboxylic acidC7H10N2O5Ee: 100%[α]D20=-69.0 (c 0.1, water/methanol 1:1)Absolute configuration: (3S,5S)Source of chirality: enzymatic resolution