The synthesis of artificial sweeteners (phenylglycine-analogues of aspartame) in order to evaluate changes in the γ-glycophore component

In order to assess the role and function of the third component (X, or γ) in the AH, B glycophore that is a prerequisite for sweet taste, its identity and position in a series of dipeptides was studied. Four isomers of aspartyl-α-phenylglycine methyl ester 4 (isomers 4a, 4b, 4c and 4d) were synthesised and their taste reveals (1) the effect of the size of γ; (2) the effect of the position of γ; and (3) the effect of the nature of γ. y evaluation showed that, as expected, only the S,S isomer, 4b, tasted sweet while the other three isomers tasted bitter. These results agree with a theory proposed by Goodman et al., 1987. Attempts to produce the analogous S-aspartyl-N-phenylglycine methyl ester, 7, by a similar route unexpectedly yielded a non-sweet dioxopiperazine derivative, 8, with a sour/bitter taste.