New Synthetic Seven‐Membered 1‐Azasugars Displaying Potent Inhibition Towards Glycosidases and Glucosylceramide Transferase

Abstract

Abstract Several members of a new family of seven‐membered azasugars, which can be seen as 1‐azasugar ring homologues, have been obtained by simple chemical transformations starting from a sugar‐derived azidolactol. Unlike their piperidine counterparts, these molecules are chemically stable when they possess a hydroxy group at the pseudo‐C‐2 position. Biological assays with a range of carbohydrate‐processing enzymes have revealed interesting potential for these compounds. A trihydroxymethyl‐substituted azepane displayed strong competitive inhibition on almond β‐glucosidase ( K i =2.5 μ M ) while a trihydroxylated carboxylic acid derivative proved to be a potent and selective L ‐fucosidase inhibitor ( K i =41 n M ). N‐Butylation of these seven‐membered 1‐azasugars generated derivatives with some activity towards the Gaucher’s disease‐related glucosylceramide transferase (IC 50 75 μ M ) that did not interact significantly with digestive glucosidases.