Trihydroxy-2-thiaquinolizidine derivatives as a new class of bicyclic glycosidase inhibitors

Trihydroxy-2-thiaquinolizidines, a new class of bicyclic dideoxy-iminohexitol glycosidase inhibitor derivatives with nominally the d -gluco, l -ido, d -manno and l -gulo configurations were synthesized. X-ray analyses indicated that the preferred conformation for d -gluco and d -manno derivatives was a flat trans-fused system. Unlike deoxynojirimycin, the compound with d -gluco configuration was selective for α-glucosidases (yeast and rice) and showed no inhibitory activity towards β-glucosidase (almond), α-galactosidase (green coffee beans), α-galactosidase (E. coli) and α-mannosidase (jack bean), while the l -ido derivative was specific for β-glucosidase (almond).