Iminoalditol-amino acid hybrids: synthesis and evaluation as glycosidase inhibitors.
Cyclization by double reductive amination of D-xylo-hexos-5-ulose with the terminal amino group of alpha-N-Boc-lysine methyl ester gave a 4:1-mixture of (1'R)-N-methoxycarbonyl-(1-N-Boc-amino)pentyl-1-deoxynojirimycin and the corresponding L-ido epimer whereas D-lyxo-hexos-5-ulose furnished the desired N-alkylated 1-deoxymannojirimycin derivative without any observable epimer formation at C-5. By subsequent modification of the lysine moiety, additional chain-extended derivatives as well as fluorescent compounds were obtained. All fluorescent iminoalditol-amino acid hybrids prepared in this study exhibited glycosidase inhibitory activities better than or comparable to the parent compounds'.
Steiner
Andreas J
AJ
Glycogroup, Institut für Organische Chemie, Technische Universität Graz, Stremayrgasse 16, A-8010 Graz, Austria.
Stütz
Arnold E
AE
Tarling
Chris A
CA
Withers
Stephen G
SG
Wrodnigg
Tanja M
TM
D000596:Amino Acids / Q000737:chemistry* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D005959:Glucosidases / Q000037:antagonists & inhibitors; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D007097:Imines; D007202:Indicators and Reagents; D007700:Kinetics; D008361:Mannosidases / Q000037:antagonists & inhibitors; D008958:Models, Molecular; D013402:Sugar Alcohols / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D000596:Amino Acids; D004791:Enzyme Inhibitors; D007097:Imines; D007202:Indicators and Reagents; D013402:Sugar Alcohols; D005959:Glucosidases; D006026:Glycoside Hydrolases; D008361:Mannosidases