1-Thio-beta-D-galactofuranosides: synthesis and evaluation as beta-D-galactofuranosidase inhibitors.
Beta-D-galactofuranosidase is a good chemotherapeutic target for the design of inhibitors, since beta-D-galactofuranose is a constituent of important parasite glycoconjugates but is not present in the host mammals. With this aim, we have synthesized for the first time alkyl, benzyl and aryl 1-thio-beta-D-galactofuranosides by condensation of penta-O-benzoyl-alpha,beta-D-galactofuranose with the corresponding thiols, in the presence of SnCl4as catalyst. The complete chemical and spectroscopical characterization of these compounds showed that the reaction was stereoselective. Debenzoylation with sodium methoxide afforded the beta-S-galactofuranosides in high yield. The thioglycosides were tested as inhibitors of the beta-D-galactofuranosidase of Penicillium fellutanum, using for the first time 4-nitrophenyl-beta-D-galactofuranoside as chromogenic substrate. The 4-aminophenyl-1-thio-beta-D-galactofuranoside, obtained by catalytic hydrogenation of the nitrophenyl derivative, was the best inhibitor being then an adequate ligand for the preparation of an affinity phase aimed at the isolation of beta-d-galactofuranosidases from different sources. Also the inhibitory activity of d-galactono-1, 4-lactone was shown.
Marino
C
C
CIHIDECAR, Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, 1428, Buenos Aires, Argentina.
Mariño
K
K
Miletti
L
L
Manso Alves
M J
MJ
Colli
W
W
de Lederkremer
R M
RM
D002863:Chromogenic Compounds / Q000378:metabolism; D005690:Galactose / Q000031:analogs & derivatives*; D005697:Galactosides / Q000378:metabolism; D010407:Penicillium / Q000201:enzymology; D013865:Thioglycosides / Q000138:chemical synthesis* / Q000494:pharmacology*; D001616:beta-Galactosidase / Q000037:antagonists & inhibitors*
D002863:Chromogenic Compounds; D005697:Galactosides; D013865:Thioglycosides; C060549:4-nitrophenylgalactofuranoside; D001616:beta-Galactosidase; D005690:Galactose