Short synthesis of new salacinol analogues and their evaluation as glycosidase inhibitors

Versatile synthesis of some analogues of the naturally-occurring alpha-glucosidase inhibitor salacinol (1), involving thioanhydro alditol moieties with erythro, D,L-threo, xylo, ribo, D-arabino and D-manno configurations is described. Nucleophilic attack at the least-hindered carbon atom of an L- or D-protected erythritol cyclic sulfate by the thioanhydro alditol sulfur atom yielded the desired zwitterionic compounds. In addition, the preparation of the cyclic sulfates of 2,4-O-benzylidene-D-erythritol and 2,4-Ow-isopropylidene-L-erythritol was improved. Enzyme inhibition tests showed that most of the new compounds were weak but specific inhibitors, while good inhibitory activity was found for a six-membered ring analogue (beta-glucosidase: K-i = 16 mu M). (c) 2005 Elsevier Ltd. All rights reserved.