Chemical and chemo-enzymatic approaches to glycosidase inhibitors with basic nitrogen in the sugar ring

Abstract

Due to the vital functions of enzymes with glycosidase and glycosyl transferase activities in living systems, inhibitors of such biocatalysts have attracted considerable interest in the recent past. Low molecular weight glycosidase inhibitors are structurally frequently related to the natural substrates or, more importantly, to the oxocarbonium ion like transition state of glycoside hydrolysis. Sugar shaped inhibitors with a basic nitrogen instead of oxygen in the ring, so-called imino sugars, by the combination of their interesting biological properties and their challenging chemical structures, are certainly one of the most attractive classes of glycosidase inhibitors known to date. While inhibitors of D-glucosidases as well as D-mannosidases have found widespread interest and have been extensively reviewed, quite a few other structurally related compounds with marked effects on other glycosidases have been discovered as natural products or synthesized. This account will attempt to survey some of these classes of compounds and cover the literature to April 1996 as available in Graz.