Synthesis of tri-and tetramines containing two 2,3-dihydroxypyrrolidine moieties and their inhibitory activity toward alpha-mannosidases

Through the reductive amination of N-[(tert-butoxy) carbonyl]-2,5-dideoxy-2,5-imino-3,4-O-isopropylidene-L-ribose with tetramethylenediamine, hexamethylenediamine, 2,7-diaminofluorene, 4,4'-diaminodiphenylmethane and 1,4-(diaminomethyl) benzene, five tetramines containing two (2R, 3R, 4S)-2-aminomethylpyrrolidine- 3,4- diol moieties have been prepared and assayed for their inhibitory activities toward 24 glycosidases. Tetramines containing the tetramethylene or benzene-1,4-dimethylene linkers are more potent amannosidase inhibitors than simple (2R, 3R, 4S)-2-aminomethylpyrrolidine- 3,4-diols. Triamines such as (2S, 3R, 4S)-bis(3,4-dihydroxy-pyrrolidin-2-ethyl) amine were also prepared and shown to be better alpha-mannosidase inhibitors than (2S, 3R, 4S)- 2-(2-aminoethyl) pyrrolidin-3,4-diol.