Synthesis of polyhydroxy piperidines and their analogues: a novel approach towards selective inhibitors of α-glucosidase

Abstract

Various polyhydroxy piperidine azasugars have been synthesized from precursors 18a and 18b, obtained in both enantiomeric forms from D-ribose. Out of these polyhydroxy piperidine azasugars, 22, 39 and 20 were found to be potent as well as selective inhibitors of α-glucosidase with K_i values ranging as low as 1.07 µM, 16.4 µM, and 88.2 µM, respectively. Replacement of the hydroxy methylene moiety of 19 (K_i 33% at 1 mM) by an amino methylene moiety (32, K_i 36.8 µM) showed a remarkable increase in the activity (almost 30 times). Furthermore, increasing the lipophilicity of 33 by N-alkylation with a dodecyl group (36) showed a three-fold enhancement in the activity (K_i 217 µM to K_i 72.3 µM).