Synthesis of an alpha-fucosidase inhibitor, 5a-carba-beta-L-fucopyranosylamine, and fucose-type alpha- and beta-DL-valienamine unsaturated derivatives

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