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.