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

Abstract

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-gluco- pyranosyl- 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 the 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.