Résumé

New 2-(aminomethyl)-5-(hydroxymethyl)pyrrolidine-3,4-diol derivatives were synthesized from (5S)-5-[(trityloxy)methyl]pyrrolidin-2-one (6) (Schemes 1 and 2) and their inhibitory activities toward 25 glycosidases assayed (Table). The influence of the configuration of the pyrrolidine ring on glycosidase inhibition was evaluated. (2R,3R,4S,5R)-2-[(benzylamino)methyl]-5-(hydroxymethyl)pyrrolidine-3,4-d iol ((+)-21) was found to be a good and selective inhibitor of a-mannosidase from jack bean (K-i=1.2 muM) and from almond (K-i= 1.0 muM). Selectivity was lost for the non-benzylated derivative (2R,3R,4S,5R)-2-(aminomethyl)-5-(hydroxymethyl)pyrrolidine-3,4-diol ((+)-22) which inhibited alpha-galactosidases, beta-galactosidases, beta-glucosidases, and alpha-N-acetylgalactosaminidase as well.

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