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.
Ogawa
Seiichiro
S
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Hiyoshi, Kohoku-ku, 223-8522, Yokohama, Japan. ogawa@applc.keio.ac.jp
Watanabe
Maiko
M
Maruyama
Ayako
A
Hisamatsu
Seiichi
S
D000818:Animals; D002417:Cattle; D053138:Cyclohexenes; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005643:Fucose / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D006595:Hexosamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000201:enzymology; D013329:Structure-Activity Relationship; D005644:alpha-L-Fucosidase / Q000037:antagonists & inhibitors*
C461193:5a-carbafucopyranosylamine; D053138:Cyclohexenes; D004791:Enzyme Inhibitors; D006595:Hexosamines; D005643:Fucose; C030791:valienamine; D005644:alpha-L-Fucosidase