Syntheses and Glycosidase Inhibitory Activities of 2‐(Aminomethyl)‐5‐(hydroxymethyl)pyrrolidine‐3,4‐diol Derivatives

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‐diol ((+)‐21) was found to be a good and selective inhibitor of α‐mannosidase from jack bean (Ki=1.2 μM) and from almond (Ki=1.0 μM). Selectivity was lost for the non‐benzylated derivative (2R,3R,4S,5R)‐2‐(aminomethyl)‐5‐(hydroxymethyl)pyrrolidine‐3,4‐diol ((+)‐22) which inhibited α‐galactosidases, β‐galactosidases, β‐glucosidases, and α‐N‐acetylgalactosaminidase as well.