Synthesis of azasugars as potent inhibitors of glycosidases.
A series of enantiomerically pure azasugars (2,5-dideoxy-2, 5-imino-D-mannitol, 1-deoxynojirimycin, 1-deoxymannojirimycin, and related compounds) was synthesized from D-mannitol via aminoheterocyclization of C2-symmetric bis-epoxides and subsequently followed by ring isomerization in few cases. These compounds have been evaluated as inhibitors of several glycosidases (alpha- and beta-D-glucosidases, alpha-D-mannosidase and alpha-L-fucosidase). Inhibition studies indicate notably that the polyhydroxylated azepanes are inhibitors of glycosidases, with Ki in the micromolar range.
Le Merrer
Y
Y
Université René Descartes, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, CNRS, Paris, France.
Poitout
L
L
Depezay
J C
JC
Dosbaa
I
I
Geoffroy
S
S
Foglietti
M J
MJ
D017485:1-Deoxynojirimycin / Q000138:chemical synthesis; D000470:Alkaloids / Q000138:chemical synthesis; D000818:Animals; D002417:Cattle; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D001411:Geobacillus stearothermophilus; D065089:Glycoside Hydrolase Inhibitors; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D050113:Imino Furanoses; D007536:Isomerism; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008353:Mannitol / Q000031:analogs & derivatives; D008956:Models, Chemical; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry*; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry*
D000470:Alkaloids; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D050113:Imino Furanoses; D010880:Piperidines; D011759:Pyrrolidines; D017485:1-Deoxynojirimycin; D008353:Mannitol; C043121:2,5-dihydroxymethyl-3,4-dihydroxypyrrolidine; D006026:Glycoside Hydrolases