A Versatile Synthetic Strategy for the Preparation and Discovery of New Iminocyclitols as Inhibitors of Glycosidases
作者:Maki Takebayashi、Sayoko Hiranuma、Yoshimi Kanie、Tetsuya Kajimoto、Osamu Kanie、Chi-Huey Wong
DOI:10.1021/jo9902446
日期:1999.7.1
A series of iminocyclitols was prepared using a versatile synthetic strategy, and their inhibition of glycosidases was evaluated using capillary electrophoresis. The study has demonstrated that remarkable specificities in enzyme inhibition can be achieved with small modifications on the aglycon side chain and the ring nitrogen. Among the compounds synthesized, (2R,3R,4R,5R)-N-methyl-2-(acetamidomethyl)-3,4-dihydroxy-5-(hydroxymethyl)pyrrolidine was found to be very potent; against beta-N-acetylhexosaminidase P with the K-i value of 80 nM.