Synthesis of new nitrogen analogues of salacinol and deoxynojirimycin and their evaluation as glycosidase inhibitors.
The synthesis of two enantiomerically pure iminosugars, analogues of 1-L-deoxynojirimycin (l-DNJ) and 1-D-deoxymannojirimycin (DMJ), was achieved using cyclic sulfate substituted isoxazoline derivatives. The piperidine ring was formed via the reduction of an isoxazoline into an amine which underwent a spontaneous intramolecular cyclization by reaction with the cyclic sulfate moiety. The nucleophilic attack of these two trisubstituted piperidines and morpholine on L- and D-erythritol-1,3-cyclic sulfates gave six new nitrogen analogues of salacinol. The inhibitory properties of the synthesized salacinol analogues were evaluated on several commercial glycosidases.
Gallienne
Estelle
E
Laboratoire SEESIB, UMR 6504 CNRS, Université Blaise Pascal, 24 avenue des Landais, 63177 Aubière Cedex, France.
Gefflaut
Thierry
T
Bolte
Jean
J
Lemaire
Marielle
M
D017485:1-Deoxynojirimycin / Q000138:chemical synthesis / Q000737:chemistry*; D000478:Alkylation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006900:Hydroxylation; D015394:Molecular Structure; D009025:Morpholines / Q000737:chemistry; D009584:Nitrogen / Q000737:chemistry*; D013402:Sugar Alcohols / Q000138:chemical synthesis / Q000737:chemistry*; D013431:Sulfates / Q000138:chemical synthesis / Q000737:chemistry*
D004791:Enzyme Inhibitors; D009025:Morpholines; D013402:Sugar Alcohols; D013431:Sulfates; C427963:salacinol; D017485:1-Deoxynojirimycin; C037574:morpholine; D006026:Glycoside Hydrolases; D009584:Nitrogen