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

Abstract

Through the reductive amination of N-[(tert-butoxy)carbonyl]-2,5-dideoxy-2,5-imino-3,4-Oisopropylidene-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 αmannosidase 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 α-mannosidase inhibitors than (2S,3R,4S)-2-(2-aminoethyl)pyrrolidin-3,4-diol.