Synthesis and evaluation of 3-deoxy and 3-deoxy-3-fluoro derivatives of gluco- and manno-configured tetrahydropyridoimidazole glycosidase inhibitors.

Three tetrahydropyridoimidazole-type glycosidase inhibitors have been synthesized with the 3-deoxy ribo- and arabino-, and 3-deoxy-3-fluoro gluco-configurations and two of them screened for activity against α- and β-gluco- and mannosidase enzymes. Only one substance, the 3-deoxy-3-fluoro-derivative of the gluco-configured tetrahydropyridoimidazole was found to have any activity against a single enzyme, sweet almond β-glucosidase, and even then at a level 100-fold lower than that of the corresponding simple gluco-configured tetrahydropyridoimidazole thereby underlining the importance of the 3-hydroxy group in the key substrate-enzyme interactions.