Synthesis of alpha-glucosidase inhibitors: kojibiose-type pseudo-disaccharides 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 alpha-glucosidase I inhibitors. Synthesis of the pseudo-disaccharides 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 alpha-glucosidase (baker's yeast), they did not have any inhibitory potency against either sucrase isomaltase (rat intestine) or processing alpha-glucosidase (rat liver microsomes).
Ogawa
S
S
Department of Applied Chemistry, Faculty of Science and Technology, Keio Univeristy, Yokohama, Japan.
Ashiura
M
M
Uchida
C
C
D000818:Animals; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D004187:Disaccharides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors; D008862:Microsomes, Liver / Q000201:enzymology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000737:chemistry; D009904:Optical Rotation; D051381:Rats; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013329:Structure-Activity Relationship; D013552:Swine; D014312:Trisaccharides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D004187:Disaccharides; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D009844:Oligosaccharides; D014312:Trisaccharides; C008237:kojibiose