Synthesis of 1,4-dideoxy-1,4-imino-D-glucitol, a glucosidase inhibitor.
1,2:5,6-Di-O-isopropylidene-D-glucitol was converted via its 1,4-dimethanesulfonate into the 1-azido-4-methanesulfonate which, after deprotection and treatment with barium hydroxide, afforded a 9:1 mixture of the corresponding 3,4- and 4,5-anhydro derivatives. Reduction of this mixture by transfer hydrogenation using ammonium formate in methanol and Pd/C as catalyst afforded 1,4-dideoxy-1,4-imino-D-glucitol (4), the structure of which was proved after acetylation by 1H-n.m.r. spectroscopy. Compound 4 is a potent alpha-D-glucosidase inhibitor (Ki 7 X 10(-4)M) and a less potent beta-D-glucosidase inhibitor (Ki 1.25 X 10(-4)M), and inhibits beta-D-galactosidase non-competitively.
D000606:Amino Sugars / Q000138:chemical synthesis* / Q000494:pharmacology; D005959:Glucosidases / Q000037:antagonists & inhibitors*; D065089:Glycoside Hydrolase Inhibitors; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008722:Methods; D010944:Plants / Q000201:enzymology; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D001616:beta-Galactosidase / Q000037:antagonists & inhibitors; D001617:beta-Glucosidase / Q000037:antagonists & inhibitors*
D000606:Amino Sugars; D065089:Glycoside Hydrolase Inhibitors; D005959:Glucosidases; D001617:beta-Glucosidase; D001616:beta-Galactosidase