Design of novel conformationally restricted analogues of glutamic acid

Stereomeric 3-carboxy-Δ2-isoxazoline–cyclopentane amino acids, which represent restricted conformations of glutamic acid, have been prepared through a strategy based on the 1,3-dipolar cycloaddition of ethoxycarbonylformonitrile oxide to a suitably protected 1-amino-cyclopent-2-enecarboxylic acid. These amino acids, assayed at iGluRs and mGluRs, proved to be inactive. The biological data have been accounted for through the comparison of their conformational profile with that of a 3-carboxy-Δ2-isoxazolinyl proline (CIP-A) and (±)-1-aminocyclopentane-1,3-dicarboxylic acid.