Design and synthesis of new sweeteners

Sweet taste induction by alkyl 2,3-di-O-(L-aminoacyloxy)-α-D-glucopyranosides requires a combination of hydrophobic α-alkoxy and hydrophilic vicinal, diequatorially ori- ented, L-aminoacyloxy units. Pyranoside chair conformations afford the preferred stereo- chemical arrangements of these residues for optimum interaction with the receptor. For the design of new sweeteners based on sweetness inhibitors, the introduction of a di-O-aminoa- cyloxy unit as the hydrogen-bonding component was applied to effect their intertransforma- tion. Thus, the known sweetness inhibitor, methyl 4,6-dichloro-4,6-dideoxy-α-D-galactopy- ranoside, was successfully transformed into sweet-tasting 2,3-di-O-(L-aminoacyl) derivatives. The inhibition of the 4,6-dichloro derivative is therefore competitive. Amongst the related amino-chloro-deoxysugars, methyl 6-chloro-6-deoxy-2,3-di-O-(L-alanyl)-α-D-gluco- pyranoside was found to be a full agonist. Our studies were then extended to disaccharide derivatives based on trehalose. This approach led to new highly intense sweeteners, as dimeric forms of the full agonist 2,3,2',3'-tetra-O-(L-alanyl)-6,6'-dichloro-6,6'-dideoxytre- halose. The derivatives with effective hydrophobic groups on the C-6 and C-6' positions, were found to be up to 800-1000 times sweeter than sucrose.