Aziridines as a structural motif to conformational restriction of azasugars.
In order to investigate the hypothesis that the glycosidase inhibitor isofagomine was bound to alpha- or beta-glucosidase in a 1,4B conformation, a number of bicyclic aziridines that adopt the 1,4B or B1,4 conformations were synthesised and investigated. (1R)-2-endo,3-exo-2,3-Dihydroxy-4-endo-4-hydroxymethyl-6- azabicyclo[3.1.0]hexane (5) and its N-methyl and N-benzyl analogues and (1S)-2-exo-3-endo-2,3-dihydroxy-4- endo-4-hydroxymethyl-6-azabicyclo-[3.1.0]hexane (6) were synthesised. The aziridines 5 and 6 were found to be weak or not inhibitors of alpha-glucosidase, beta-glucosidase and alpha-fucosidase.
Lopez Lopez
Oscar
O
Department of Chemistry, University of Aarhus, Langelandsgade 140, DK-8000 Aarhus, Denmark.
Fernández-Bolaños
José G
JG
Lillelund
Vinni H
VH
Bols
Mikael
M
D000818:Animals; D001388:Aziridines / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D002417:Cattle; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors; D050112:Imino Pyranoses; D008968:Molecular Conformation; D010880:Piperidines / Q000494:pharmacology; D027861:Prunus / Q000201:enzymology; D015003:Yeasts / Q000201:enzymology; D000520:alpha-Glucosidases / Q000378:metabolism; D005644:alpha-L-Fucosidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D001617:beta-Glucosidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D001388:Aziridines; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D050112:Imino Pyranoses; D010880:Piperidines; C098432:isofagomine; D000520:alpha-Glucosidases; D001617:beta-Glucosidase; D005644:alpha-L-Fucosidase