Synthesis of an α-Fucosidase Inhibitor, 5a-Carba-β- -fucopyranosylamine, and Fucose-Type α- and β- -Valienamine Unsaturated Derivatives

Discovery of a very potent α-fucosidase inhibitor 5a-carba-α- -fucopyranosylamine (1) led to preparation of its β-anomer Figure 1 and Scheme 1 and the respective unsaturated derivatives, fucose-type α- and β-valienamines ( Figure 1 and Scheme 2 and Figure 1 and Scheme 2), in order to elucidate the structure–activity relationship of carba-aminosugar inhibitors of this kind. Compound Figure 1 and Scheme 1 was demonstrated to be a potent inhibitor (Ki=2.0 × 10−7 M, bovine kidney), possessing ca. one-tenth of the activity of the parent 1. Interestingly, Figure 1 and Scheme 2 and Figure 1 and Scheme 2 were found to be rather weak inhibitors, contrary to the expectations based on the activity relationships between the α-glucosidase inhibitors, α-glucose-type validamine and valienamine.