Synthesis of iminoalditol analogues of galactofuranosides and their activities against glycosidases.
Iminoalditol analogues of galactofuranosides were synthesized from 1-C-(2'-oxo-propyl)-1,4-dideoxy-1,4-imino-d-galactosides and different amines by reductive amination, followed by removal of protecting groups. The activity of these compounds against galactosidases and other glycosidases was investigated. The best inhibitor against beta-galactosidase (bovine liver) is a diastereomeric mixture of an iminoalditol (10h), which contains a hydrophobic hexadecyl aglycon (R=C(16)H(33)), whereas no significant inhibitory activity was observed with compounds having a hydrophilic aglycon. Surprisingly, activation of alpha-galactosidase (coffee bean) by 10h was also observed. Because these results were obtained from a mixture of iminoalditols, the inhibition and activation of glycosidases could result from different diastereomers.
Sandbhor
Mahendra
M
Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada K1A 0R6.
Bhasin
Milan
M
Williams
Dean T
DT
Hsieh
Margaret
M
Wu
Shih-Hsiung
SH
Zou
Wei
W
D017485:1-Deoxynojirimycin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000627:therapeutic use; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D005690:Galactose / Q000031:analogs & derivatives / Q000138:chemical synthesis; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000378:metabolism; D006027:Glycosides / Q000737:chemistry; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008958:Models, Molecular; D013402:Sugar Alcohols / Q000138:chemical synthesis / Q000737:chemistry
D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D006027:Glycosides; D007004:Hypoglycemic Agents; D013402:Sugar Alcohols; C045621:miglitol; D017485:1-Deoxynojirimycin; D006026:Glycoside Hydrolases; D005690:Galactose