Synthesis and glycosidase inhibitory activities of 2-(aminoalkyl)pyrrolidine-3,4-diol derivatives Original Research Article

Several 2-(aminomethyl)-and 2-(2-aminoethyl)-pyrrolidine-3,4-diol derivatives have been assayed for their inhibitory activities towards glycosidases. Good inhibitors of α-mannosidases must have the (2R,3R,4S) configuration and possess 2-(benzylamino)methyl substituents. Stereomers with the (2S,3R,4S) configuration are also competitive inhibitors of α-mannosidases, but less potent as they share the configuration of C(1), C(2), C(3) of β-d-mannosides rather than that of α-d-mannosides. Interestingly, (2S,3R,4S)-2-{2-[(4-phenyl)phenylamino]ethyl}pyrrolidine-3,4-diol (12g) inhibits several enzymes, for instance α-l-fucosidase from bovine epididymis (Ki=6.5 μM, competitive), α-galactosidase from bovine liver (Ki=5 μM, mixed) and α-mannosidase from jack bean (Ki=102 μM, mixed). Diamines such as (2R,3S,4R)-2-[2-(phenylamino) or 2-(benzylamino)ethyl]pyrrolidine-3,4-diol (ent-12a, ent-12b) inhibit β-glucosidase from almonds (Ki=13–40 μM, competitive).