Abstract
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.
Highlights
Cell sociology involves a language based on molecular recognition between cell-surface carbohydrates and proteins.1 The biosynthesis of the surface oligosaccharides uses glycosyltransferases and glycosidases as catalysts
We report here the synthesis of five tetramines 4 (Figure 2)
Synthesis of the polyamines Tetramines 4 were all prepared from aldehyde 68 by reaction with the corresponding diamine H2N-A-NH2 (1.8 equivalent) in the presence of NaBH(OAc)322 for in situ reduction of the resulting diimine intermediate (Scheme 1)
Summary
Cell sociology involves a language based on molecular recognition between cell-surface carbohydrates and proteins.1 The biosynthesis of the surface oligosaccharides uses glycosyltransferases and glycosidases as catalysts. Glycosidase inhibitory activities Appropriate p-nitrophenyl pyranosides were used as substrates and commercially available glycosidases (see below and Table) were used as catalysts of the buffered hydrolysis under optimal pH.25 At 1 mM concentration and under optimal pH conditions tetramines 4 and triamines 5 and ent-5 did not inhibit the following enzymes: α-L-fucosidase from bovine epididymis, α-D-galactosidases from coffee bean, Aspergillus niger and E. coli, β-galactosidase from orizae, β-D-mannosidase from Helix pomatia, β-N-acetylgalactosamidase from jack bean, bovine epididymis A and B. The bad surprise is that these tetramines inhibit other glycosidases, moderately though, except for 4a which is a good, non-competitive inhibitor of β-glucosidase from almond.
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