A preparation and screening strategy for glycosidase inhibitors

Here we present a one-pot procedure for the synthesis of a library of carbohydrate compounds belonging to four classes of glycosidase inhibitors: glycosides, aldonic acid lactams, aldonic acid lactones and dideoxy-iminoalditols. The complex mixture was separated into individual components that were screened for activity against α- and β-glucosidases. Among these were two 2-O-methyl glycosides that reduced the rate of the enzymatically-catalyzed hydrolysis of the p-nitrophenyl glucosides used in the assay. Relative inhibition indices normalized to the inhibition observed with deoxynojirimycin under similar conditions were determined. This methodology provides a straightforward, general and time-efficient way to synthesize, test and analyze an extensive number of glycosidase inhibitor candidates from several carbohydrate compound classes in one scheme. The direct reference to deoxynojirimycin gives an immediate indication of the concentration range in which a significant inhibitory activity can be obtained.