alpha- and beta-homogalactonojirimycins (alpha- and beta-homogalactostatins): synthesis and further biological evaluation.
The homoiminosugars alpha- and beta-homogalactonojirimycins were prepared from a common intermediate, tetra-O-benzyl-D-galacto-heptenitol 6, by way of highly stereoselective reaction sequences involving, as the key steps, an internal amidomercuration (alpha-epimer) and a double reductive amination (beta-epimer). alpha-Homogalactonojirimycin retains a large part of the potent activity of the parent galactonojirimycin and 1-deoxygalactonojirimycin as an inhibitor of alpha-galactosidases. However, by contrast with the parent iminosugars, it does not inhibit beta-galactosidases, with the exception of the Jack beans enzyme. beta-Homogalactonojirimycin is a weak alpha-galactosidase inhibitor and is completely devoid of activity towards beta-galactosidases. Thus, a marked selectivity toward one family of enzymes has been achieved by the addition of an alpha-CH(2)OH group in the structure of the parent iminosugars.
Martin
O R
OR
Department of Chemistry, State University of New York, Binghamton, NY 13902-6016, USA. olivier.martin@univ-orleans.fr
Saavedra
O M
OM
Xie
F
F
Liu
L
L
Picasso
S
S
Vogel
P
P
Kizu
H
H
Asano
N
N
D000586:Amination; D000818:Animals; D002460:Cell Line / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D005688:Galactosamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007313:Insecta / Q000166:cytology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000519:alpha-Galactosidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001616:beta-Galactosidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004791:Enzyme Inhibitors; C051195:5-amino-5-deoxygalactopyranose; D005688:Galactosamine; D000519:alpha-Galactosidase; D001616:beta-Galactosidase