N-FORMYLCARBAMOYLASPARTAME, A NEW ASPARTAME-LIKE SWEETENER - SYNTHESIS AND STUDIES ON STABILITY AND BIOLOGICAL PROPERTIES

A new aspartame-like sweetener, N-formylcarbamoylaspartame (FC-APM), was efficiently prepared from aspartame (APM). Due to the N-protective group, FC-APM is less prone to diketopiperazine formation and therefore much more stable than aspartame at higher pH values (6-9) and temperatures (60-80-degrees-C). In vitro biotransformation experiments in tissue fractions of the rat gastrointestinal tract showed that FC-APM is less efficiently metabolized compared to APM. A relatively stable metabolite of FC-APM was isolated from tissue extracts by preparative HPLC and identified by C-13 NMR as the demethylated product of FC-APM. FC-APM did not show mutagenic activity in the Salmonella/microsome assay either with or without metabolic activation. In the Sister Chromatid Exchange (SCE) test, FC-APM did increase human lymphocyte SCE frequency significantly but not dose dependently, while application of a metabolic system prevented these chromosome-damaging effects.