N‐Thiocarbonyl Iminosugars: Synthesis and Evaluation of Castanospermine Analogues Bearing Oxazole‐2(3H)‐thione Moieties

Abstract

AbstractA straightforward and efficient synthetic route to a new class of glycosidase inhibitors containing an oxazole‐2(3H)‐thione moiety has been devised. The approach involves the formation of α‐hydroxy ketones, which, after condensation with thiocyanic acid, leads to the formation of the heterocycle. By exploiting the ability of the nitrogen atom of oxazoline‐2‐thione precursors to act as nucleophiles in intramolecular addition, castanospermine analogues could be readily prepared in good overall yields. Glycosidase inhibitory activity compared to oxazolidinethione analogues showed a strong influence of the double bond, for example with pseudoiminosugar 19, by suppressing α‐glucosidase inhibition and introducing, to a moderate level, β‐glucosidase inhibitory activity. Reactivities showed the propensity of oxazole‐2(3H)‐thiones – especially when fused on carbohydrate frames – to convert into 1,3‐oxazolidine‐2‐thione aminals through nucleophilic addition to the double bond, leading to unexpected tricyclic structure 21.