Synthesis of S-alkylated sulfonium-ions and their glucosidase inhibitory activities against recombinant human maltase glucoamylase

The syntheses of nine S-alkylated, cyclic sulfonium-ions with varying alkyl chain lengths, as mimics of N-alkylated imino sugars, and their glucosidase inhibitory activities are described. The target compounds were synthesized by alkylation of 2,3,5-tri-O-benzyl-1,4-anhydro-4-thio-D-arabinitol at the ring sulfur atom using various alkyl halides, followed by deprotection using boron trichloride. Enzyme inhibitory assays against recombinant human maltase glucoamylase (NIGA), a critical enzyme in the small intestine involved in the breakdown of glucose oligosaccharides into glucose itself, shows that they are effective inhibitors of MGA with K-i values ranging from 6 to 75 mu M. (c) 2007 Elsevier Ltd. All rights reserved.