Design and synthesis of new sweeteners*
Tomoya Machinami1,**, Takashi Fujimoto1, Aya
Takatsuka1, Takeshi Mitsumori1, Takako Toriumi1,
Tetsuo Suami 2, and Leslie Hough 3
1Department of Chemistry, College of Science and Technology,
Meisei University, Hino, Tokyo 191-8506, Japan; 2Department of Applied
Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi,
Yokohama 223-0061, Japan; 3Department of Chemistry, King's College London,
University of London, Strand, London WC2R 2LS, UK
Abstract: Sweet taste induction by alkyl 2,3-di-O-(l-aminoacyloxy)-a-D-glucopyranosides
requires a combination of hydrophobic a-alkoxy
and hydrophilic vicinal, diequatorially oriented, L-aminoacyloxy
units. Pyranoside chair conformations afford the preferred stereochemical
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-aminoacyloxy unit as the hydrogen-bonding
component was applied to effect their intertransformation. Thus, the
known sweetness inhibitor, methyl 4,6-dichloro-4,6-dideoxy-a-D-galactopyranoside,
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)-a-D-gluco-pyrano
side 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'
-dideoxytrehalose. The derivatives with effective hydrophobic groups
on the C-6 and C-6' positions, were found to be up to 8001000
times sweeter than sucrose.
* A special topic issue on the
science of sweeteners.
** Corresponding author.
