Aspartame analogues containing 1-amino-2-phenylcyclohexanecarboxylic acids (c6Phe). Part 2

Abstract

This report describes the synthesis and conformational analysis of optically pure dipeptide analogues of aspartame, namely H-(S)-Asp-(1R,2S)-c6Phe-OMe and H-(S)-Asp-(1S,2R)-c6Phe-OMe, in which the Phe residue of aspartame has been replaced by a restricted Phe with a cyclohexane skeleton: 1-amino-2-phenylcyclohexanecarboxylic acid (c6Phe). The dipeptide that incorporates (1R,2S)-c6Phe is sweet whereas the compound that incorporates (1S,2R)-c6Phe is bitter. This relationship between the absolute configuration of the dipeptides and the properties is explained in terms of the different conformational behaviour displayed by each molecule, as determined by molecular mechanics and molecular dynamics calculations that take into account solvent effects.