IN THE PURSUIT OF A BETTER SWEETENER

Dipeptide sweeteners of the AspNHCH(R1)COR type, where R1 = H, Me, CH2OH, and CO2Me and R = OR2 or NHR2 with R2 less-than-or-equal-to C10 atoms, i.e., alkyl, aryl, heterocyclic, bi- or tricyclic group, were synthesized to remedy the well-known shortcomings of aspartame. For the design of these sweeteners, the classic theory of Cohn-Oertly-Myers, Ariyoshi's rule of steric size difference, Newman's rule of H-6 number as well as our C-9 rule and a model of induced fitting of multiple-point attachment with the sweet receptor were employed. On the basis of our results as well as those of others, qualitative and semi-quantitative structure-activity relationships were discussed according to the current concepts of polar-steric-hydrophobic factor analyses for the pursuit of an ideal high sweetness potency dipeptide sweetener. Compounds of high sweetness potency prepared in this work are all of high stabilities and indifferent to microorganisms or any known genetic diseases.