Anomer-selective glycosidase inhibition by 2-N-alkylated 1-azafagomines.
Alkylation of 1-azafagomine at the 2-N position was achieved by reductive amination of 1-N-acetyl-3,4,6-tri-O-benzyl-1-azafagomine by using aldehydes, palladium hydroxide, and hydrogen in EtOAc/water/acetic acid followed by deprotection. The 2-N-butyl, hexyl, heptyl, nonyl, decyl, and 3-phenylpropyl derivatives were made in this manner, and were tested for inhibition of alpha-glucosidase from yeast, and of beta-glucosidase from almonds. The new compounds were stronger beta-glucosidase inhibitors than 1-azafagomine, but weaker alpha-glucosidase inhibitors.
Lopez Lopez
Oscar
O
Department of Chemistry, University of Aarhus, Langelandsgade 140, 8000 Aarhus, Denmark.
Bols
Mikael
M
D000447:Aldehydes; D000478:Alkylation; D000586:Amination; D000606:Amino Sugars / Q000138:chemical synthesis* / Q000494:pharmacology*; D002384:Catalysis; D002855:Chromatography, Thin Layer; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D006859:Hydrogen / Q000737:chemistry; D007202:Indicators and Reagents; D007536:Isomerism; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular; D010165:Palladium; D013329:Structure-Activity Relationship
D000447:Aldehydes; D000606:Amino Sugars; D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D010165:Palladium; D006859:Hydrogen; D006026:Glycoside Hydrolases