Synthesis of novel pyrrolidine 3,4-diol derivatives as inhibitors of α-L-fucosidases

Abstract

The stereoselective synthesis of new 3,4-dihydroxypyrrolidine derivatives starting from D-mannose, D-ribose and L-fucose is presented. Two synthetic strategies employing organometallic addition to hemiacetalic sugars followed by selective nucleophilic displacement or conjugate addition of ammonia to conjugate aldonic esters as key steps, are used. The new compounds were assayed for their inhibitory activity towards 13 commercially available glycosidases. Compounds that share the absolute configuration at C(2,3,4,5) of L-fucopyranosides and incorporate aromatic moieties are potent and selective inhibitors of α-L-fucosidases in the nM range.