Enzymic synthesis of alpha- and beta-D-glucosides of 1-deoxynojirimycin and their glycosidase inhibitory activities.
1-Deoxynojirimycin (1) is a potent inhibitor of mammalian and rice alpha-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 alpha-glucosidase, yeast alpha- and beta-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 alpha-glucosidase afforded 3-O-alpha-D-glucopyranosyl-N-(benzyloxycarbonyl)-1-deoxynojirimycin (4), 4-O-alpha-D-glucopyranosyl-N-(benzyloxycarbonyl)-1-deoxynojirimycin (5), and 2-O-alpha-D-glucopyranosyl-N-(benzyloxycarbonyl)-1-deoxynojirimycin (3) in yields of 40, 13, and 2%, respectively, after 30 min. The transglucosylation reaction using immobilized rice alpha-glucosidase was similar to that using the native enzyme. In the system using native yeast alpha-glucosidase, 3, 5, and 4 were formed in yields of 34, 13, and 6%, respectively, after 15 h. The immobilization of yeast alpha-glucosidase caused a significant decrease in transglucosylation activity. Yeast beta-glucosidase showed a high transglucosylation activity and incubation with the reaction system afforded 2-O-beta-D-glucopyranosyl-N-(benzyloxycarbonyl)-1-deoxynojirimycin (6) and 4-O-beta-D-glucopyranosyl-N-(benzyloxycarbonyl)-1-deoxynojirimycin (7) in yields of 69 and 3%, respectively, after 3 h. The transglucosylation reaction using immobilized yeast beta-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-alpha-D-Glucopyranosyl-1-deoxynojirimycin (9) retained the potent inhibition of 1 against rat intestinal sucrase activity and was more effective than 1 against rice alpha-glucosidase. 4-O-alpha-D-Glucopyranosyl-1-deoxynojirimycin (10) retained the potency of 1 against rat intestinal sucrase and isomaltase. 2-O-alpha-D-Glucopyranosyl-1-deoxynojirimycin (8) was more effective than 1 against trehalases.
School of Pharmacy, Hokuriku University, Ishikawa, Japan.
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N
Asano
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Oseki
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E
Kaneko
K
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Matsui
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D004800:Enzymes, Immobilized / Q000378:metabolism; D005960:Glucosides / Q000138:chemical synthesis* / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D006031:Glycosylation; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008297:Male; D008322:Mammals; D009754:Nuts / Q000201:enzymology; D012275:Oryza / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D012248:Rhodotorula / Q000201:enzymology; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D013329:Structure-Activity Relationship; D013379:Substrate Specificity; D013552:Swine; D014198:Trehalase / Q000037:antagonists & inhibitors; D000520:alpha-Glucosidases / Q000378:metabolism; D001617:beta-Glucosidase / Q000037:antagonists & inhibitors*
D004800:Enzymes, Immobilized; D005960:Glucosides; D065089:Glycoside Hydrolase Inhibitors; D011994:Recombinant Proteins; D017485:1-Deoxynojirimycin; D006026:Glycoside Hydrolases; D000520:alpha-Glucosidases; D001617:beta-Glucosidase; D014198:Trehalase