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 synth esised 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 inh ibitor, (1S,2S)-1-methylcyclopropane 1,2-dicarboxylic acid, is consist ent with it acting as a transition state analogue for the central subs trate deamination reaction catalysed by the enzyme.