Synthesis of α-glucosidase inhibitors: kojibiose-type pseudodisaccharides and a related pseudotrisaccharide

Two kojibiose-type pseudo-disaccharides and a trisaccharide, containing a 5-amino-1,2,3,4-cyclopentanetetrol derivative or valienamine, linked by way of nitrogen bridges to the sugar residues, have been designed and synthesized as processing α-glucosidase I inhibitors. Synthesis of the pseudodisaccharides was carried out starting from the coupling products of the sugar isothiocyanates and an aminocyclitol, respectively, by cyclization with mercury(II) oxide to the cyclic isoureas and subsequent deprotection. Pseudokojibiose was prepared in a poor yield by reaction of a protected valienamine and a sugar epoxide, followed by deprotection. Although the pseudooligosaccharides are all strong inhibitors of α-glucosidase (baker’s yeast), they did not have any inhibitory potency against either sucrase isomaltase (rat intestine) or processing α-glucosidase (rat liver microsomes).