Evaluation of 6‐Deoxy–amino–sugars as Potent Glycosidase Inhibitors. Importance of the CH 2 OH(6) Group for Enzyme‐Substrate Interaction

Abstract Optically active or racemic 6‐deoxy‐analogues of the nojirimycine d ‐ 1 a in allose, glucose, fucose, talose and gulose series were evaluated as glycosidase inhibitors. These compounds were analysed either as their sulfite adducts or as the “true” amino‐sugars (the exact copies of aldoses with intracyclic oxygen replaced by nitrogen) or as their reduced 1‐deoxy‐form depending on the series. Some compounds are potent inhibitors of α‐ and β‐ d ‐glucosidases and α‐ and β‐ d ‐galactosidases. Racemic compounds in talose and gulose series were also micromolar inhibitors of α‐ l ‐fucosidase and β‐ d ‐galactosidase, while the talose analogues were active against β‐ d ‐mannosidase. Comparison of these inhibition data with those of amino‐hexoses possessing the CH 2 OH group permitted to evaluate the implication of the C(6)‐OH in enzyme‐inhibitor interactions, which seem to occur particularly with α‐ d ‐glucosidase (yeast) and α‐ d ‐galactosidase (green coffee beans). The cases of the β‐ d ‐glucosidase and β‐ d ‐galactosidase were discussed.