Chemical modification of the sugar part of methyl acarviosin: synthesis and inhibitory activities of nine analogues.
Nine analogues of methyl acarviosin (1), the core structure of acarbose and its homologues, the 6-hydroxy-(2), 6-azido-(3), 6-amino- (4), 6-acetamido-(5), 6-methoxy-(6), 6-hydroxy-2-O-methyl-(8), and 6-hydroxy-3-O-methyl derivatives (9), including the 5-methoxycarbonyl analogue (7) and 3,6-anhydro derivative (10) of 2, were synthesized by chemical modification of the sugar part of 2 derived by condensation of methyl 3,4-anhydro-alpha-D-galactopyranoside (17) and 4,7:5,6-di-O-isopropylidenevalienamine (26) or by direct coupling between 26 and the 6-substituted methyl 3,4-anhydro-alpha-D-galactopyranoside derivatives. Compounds 2 and 8 show notable inhibitory activity against yeast alpha-D-glucosidase almost comparable to that of 1. Introduction of a polar substituent at C-6 of 1 decreases the inhibitory activity. Interestingly, inversion of the conformation of the sugar part of 1 by introduction of the 3,6-anhydro bridge elicits almost no effect on the inhibitory activity.
Shibata
Y
Y
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama, Japan.
Kosuge
Y
Y
Mizukoshi
T
T
Ogawa
S
S
D000606:Amino Sugars / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors; D015394:Molecular Structure
D000606:Amino Sugars; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; C076099:acarviosine