Synthesis and glycosidase inhibitory activities of 2-(aminoalkyl)pyrrolidine-3,4-diol derivatives.
Several 2-(aminomethyl)-and 2-(2-aminoethyl)-pyrrolidine-3,4-diol derivatives have been assayed for their inhibitory activities towards glycosidases. Good inhibitors of alpha-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 alpha-mannosidases, but less potent as they share the configuration of C(1), C(2), C(3) of beta-D-mannosides rather than that of alpha-D-mannosides. Interestingly, (2S,3R,4S)-2-[2-[(4-phenyl)phenylamino]ethyl]pyrrolidine-3,4-diol (12g) inhibits several enzymes, for instance alpha-L-fucosidase from bovine epididymis (K(i)=6.5microM, competitive), alpha-galactosidase from bovine liver (K(i)=5microM, mixed) and alpha-mannosidase from jack bean (K(i)=102microM, mixed). Diamines such as (2R,3S,4R)-2-[2-(phenylamino) or 2-(benzylamino)ethyl]pyrrolidine-3,4-diol (ent-12a, ent-12b) inhibit beta-glucosidase from almonds (K(i)=13-40microM, competitive).
Carmona
Ana T
AT
Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, E-41071, Seville, Spain.
Popowycz
Florence
F
Gerber-Lemaire
Sandrine
S
Rodríguez-García
Eliazar
E
Schütz
Catherine
C
Vogel
Pierre
P
Robina
Inmaculada
I
D000818:Animals; D002417:Cattle; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D008099:Liver / Q000201:enzymology; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013057:Spectrum Analysis
D004791:Enzyme Inhibitors; D011759:Pyrrolidines; D006026:Glycoside Hydrolases