New synthetic seven-membered 1-azasugars displaying potent inhibition towards glycosidases and glucosylceramide transferase

Several members of a new family of seven-membered azasugars, which can be seen as 1-azasugar ring homologues, have been I 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 beta-glucosidase (K-i = 2.5 mu M) while a trihydroxylated corboxylic acid derivative proved to be a potent and selective L-fucosidase inhibitor K-i = 41 nM). N-Butylation of these seven-membered 1-azasugars generated derivatives with some activity towards the Gaucher's disease-related glucosylceramide transferase (IC50) 75 mu M) that did not interact significantly with digestive glucosidases.