Synthesis and evaluation of alpha-fucosidase inhibitory activity of 5a-carba-alpha-L-fucopyranose and alpha-DL-fucopyranosylamine.
5a-Carba-alpha-L-fucopyranose and -alpha-DL-fucopyranosylamine were synthesized in conventional manner starting from 2,3,4-tri-O-acetyl-6-bromo-6-deoxy-5a-carba-beta-D- and -DL-glucopyranosyl bromides, respectively, and assayed for inhibitory activity against alpha-fucosidase (bovine kidney). Although the former proved to be only a moderate inhibitor (Ki = 4.3 x 10(-5) M), the latter could be shown to possess strong inhibitory potential (Ki = 2.3 x 10(-7) M). Diastereoisomeric imino-linked 5a'-carbadisaccharides were synthesized by coupling of the racemic 5a-carba-alpha-fucopyranosylamine and 1,6:3,4-dianhydro-2-azido-2-deoxy-beta-D-galactopyranose, in order to estimate approximately the inhibitory activity of individual optical antipodes of 5a-carba-alpha-fucopyranosylamine.
Ogawa
S
S
Department of Applied Chemistry, Faculty of Science and Engineering, Keio University, Yokohama, Japan.
Sekura
R
R
Maruyama
A
A
Odagiri
T
T
Yuasa
H
H
Hashimoto
H
H
D000818:Animals; D002417:Cattle; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005643:Fucose / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D066298:In Vitro Techniques; D007294:Inositol / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D005644:alpha-L-Fucosidase / Q000037:antagonists & inhibitors*
C434827:5a-carbafucopyranose; D004791:Enzyme Inhibitors; C434826:fucopyranosylamine; D005643:Fucose; C042908:validamine; D007294:Inositol; D005644:alpha-L-Fucosidase