Rapid Diversity-Oriented Synthesis in Microtiter Plates for In Situ Screening: Discovery of Potent and Selective α-Fucosidase Inhibitors

摘要

Polyhydroxypiperidines and pyrrolidines (also called iminocyclitols or aza-sugars) have attracted increasing attention because of their inhibitory activity against various glycosidases. The glucose-type iminocyclitol deoxynojirimycin (DNJ), for example, has been used for the treatment of noninsulin-dependent diabetes (miglitol, targeting the intestinal disaccharidases). Recent studies further indicate that DNJ and its derivatives are effective against hepatitis B and C, as well as glycosphingolipid storage disorders (such as Gaucher disease). The efficacy of iminocyclitols is attributed to their mimicry of the transition state of enzymatic glycosidic cleavage.