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

• Published in: Bioorganic & Medicinal Chemistry, vol. 11, num. 23, p. 4897-4911
• Publication date: 2003

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 = 6.5 muM, competitive), alpha-galactosidase from bovine liver (K-i = 5 muM, mixed) and alpha-mannosidase from jack bean (K-i = 102 muM, mixed). Diamines such as (2R,3S,4R)-2-[2-(phenylamino) or 2-(benzylamino)ethyl]pyrrolidine-3,4-diol (ent-1 2a, ent-12b) inhibit P-glucosidase from almonds (K-i = 13-40 muM, competitive). (C) 2003 Elsevier Ltd. All rights reserved.

Keywords: aza-c-disaccharides ; biological evaluation ; asymmetric-synthesis ; sugarmimics ; castanospermine ; mannosidase ; swainsonine ; discovery ; 2 ; 5-dideoxy-2 ; 5-imino-d-mannitol ; iminodisaccharides

Reference

• LGSA-ARTICLE-2003-013
• View record in Web of Science

Record created on 2005-11-09, modified on 2017-05-12