Conformationally Restricted Analogs of Antiaspartame-type Sweeteners

The synthesis and characterization of the two diastereomeric dipeptides Ac-L-(alphaMe)Phe-L-Lys-OH (5) and Ac-D-(alphaMe)Phe-L-Lys-OH (6), conformationally restricted analogues of 'anti-aspartame-type' sweeteners, are described. Both compounds are tasteless. The X-ray diffraction structure of 6, also reported in this paper, in conjunction with the sweet perception model, as developed by Temussi, Toniolo and co-workers, is used to explain the lack of sweet taste of these compounds. The two diastereomeric synthetic intermediates Ac-L-(alphaMe)Phe-L-Lys(Z)-OBu(t) (9) and Ac-D-(alphaMe)-Phe-L-Lys(Z)-OBu(t) (10) have also been characterized by X-ray diffraction.