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

Org Biomol Chem. 2008 Jul 21;6(14):2587-95. doi: 10.1039/b804278k. Epub 2008 May 20.

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 alpha-glucosidase with K(i) values ranging as low as 1.07 microM, 16.4 microM, and 88.2 microM, respectively. Replacement of the hydroxy methylene moiety of (K(i) 33% at 1 mM) by an amino methylene moiety (32, K(i) 36.8 microM) showed a remarkable increase in the activity (almost 30 times). Furthermore, increasing the lipophilicity of by N-alkylation with a dodecyl group (36) showed a three-fold enhancement in the activity (K(i) 217 microM to K(i) 72.3 microM).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspergillus / drug effects
  • Aspergillus / enzymology
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Glycoside Hydrolase Inhibitors*
  • Piperidines / chemical synthesis*
  • Piperidines / chemistry
  • Piperidines / pharmacology*
  • Substrate Specificity

Substances

  • Enzyme Inhibitors
  • Glycoside Hydrolase Inhibitors
  • Piperidines