SYNTHESIS OF PSEUDO-OLIGOSACCHARIDE GLYCOSIDASE INHIBITORS .10. CHEMICAL MODIFICATION OF THE SUGAR PART OF METHYL ACARVIOSIN - SYNTHESIS AND INHIBITORY ACTIVITIES OF 9 ANALOGS

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-3-0-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.