Enzymic synthesis of α- and β-D-glucosides of 1-deoxynojirimycin and their glycosidase inhibitory activities

Article abstract of DOI:10.1016/0008-6215(94)84091-1

1-Deoxynojirimycin (1) is a potent inhibitor of mammalian and rice α- glucosidase. Several glucosides of 1 were synthesized by use of the native and immobilized enzyme and their effect on various enzymes was investigated. Transglucosylation reactions using rice α-glucosidase, yeast α- and β- glucosidases purified from Rhodotorula lactosa were performed with maltose or cellobiose as a glucose donor and N-(benzyloxycarbonyl)-1-deoxynojirimycin (2) as an acceptor. The transglucosylation reaction using native rice α- glucosidase afforded 3-O-α-D-glucopyranosyl-N-(benzyloxycarbonyl)-1- deoxynojirimycin (4), 4-O-α-D-glucopyranosyl-N-(benzyloxycarbonyl)-1- deoxynojirimycin (5), and 2-O-α-D-glucopyranosyl-N-(benzyloxycarbonyl)-1- deoxynojirimycin (3) in yields of 40, 13, and 2%, respectively, after 30 min. The transglucosylation reaction using immobilized rice α-glucosidase was similar to that using the native enzyme. In the system using native yeast α- glucosidase, 3, 5, and 4 were formed in yields of 34, 13, and 6%, respectively, after 15 h. The immobilization of yeast α-glucosidase caused a significant decrease in transglucosylation activity. Yeast β-glucosidase showed a high transglucosylation activity and incubation with the reaction system afforded 2-O-β-D-glucopyranosyl-N-(benzyloxycarbonyl)-1- deoxynojirimycin (6) and 4-O-β-D-glucopyranosyl-N-(benzyloxycarbonyl)-1- deoxynojirimycin (7) in yields of 69 and 3%, respectively, after 3 h. The transglucosylation reaction using immobilized yeast β-glucosidase preferentially afforded 6 in a yield of 73% after 3 h. After removal of N- benzyloxycarbonyl group from the product glucosides, their glycosidase inhibitory activities were measured. 3-O-α-D-Glucopyranosyl-1- deoxynojirimycin (9) retained the potent inhibition of 1 against rat intestinal sucrase activity and was more effective than 1 against rice α- glucosidase. 4-O-α-D-Glucopyranosyl-1-deoxynojirimycin (10) retained the potency of 1 against rat intestinal sucrase and isomaltase. 2-O-α-D- Glucopyranosyl-1-deoxynojirimycin (8) was more effective than 1 against trehalases. 1-Deoxynojirimycin (1) is a potent inhibitor of mammalian and rice α-glucosidase. Several glucosides of 1 were synthesized by use of the native and immobilized enzyme and their effect on various enzymes was investigated. Transglycosylation reactions using rice α-glucosidase, yeast α and B-glucosidases purified from Rhodotorula lactosa were performed with maltose or cellobiose as a glucose donor and N-(benzyloxycarbonyl)-1-deoxynojirimycin (2) as an acceptor. The immobilization of yeast α-glucosidasse caused a significant decreased in transglucosylation activity.