Synthesis and mode of action of 1-substituted trans-cyclopropane 1,2-dicarboxylic acids: Inhibitors of the methylaspartase reaction

A range of 1-substituted cyclopropane 1,2-dicarboxylic acids are synthesised using short efficient routes and are found to be good to potent inhibitors of 3-methylaspartase; the crystallographically determined absolute stereochemistry and the mode of action of the most potent inhibitor, (1S,2S)-1-methylcyclopropane 1,2-dicarboxylic acid, is consistent with it acting as a transition state analogue for the central substrate deamination reaction catalysed by the enzyme.