Structure-activity relations for imidazo-pyridine-type inhibitors of beta-D-glucosidases

The triazole 7 and the known gluco- and manno-configurated imidazoles 10 and 11 have been prepared by annulation of the azole ring to the aldonothiolactam 14 in a Hg(OAc)(2)-promoted reaction with either hydrazine-carbaldehyde or aminoacetaldehyde dimethyl acetal. Depending upon the reaction conditions, the synthesis of the imidazoles yielded mostly the gluco-imidazole 19 or a mixture of the gluco/manno epimers 19/20. In contrast to the triazole 4, the isomeric triazole 7 proved a good inhibitor of retaining beta-glucosidases from sweet almonds and From Caldocellum saccharolyticum. This observation and the qualitative correlation between basicity and inhibitory power of the tetrahydropyridoazoles provide further evidence for the hypothesis of the 'lateral protonation' of glycosides by (some) retaining beta-glucosidases.