Issue in Honor of Prof. Rosa Lederkremer ARKIVOC 2005 (xii) 341-351
Synthesis of heteroaryl 1-thio-ß-D-galactofuranosides and evaluation of their inhibitory activity towards a ß-D-galactofuranosidase
Karina Mariño and Carla Marino*
CIHIDECAR (CONICET), Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires. Pabellón II, Ciudad Universitaria, 1428 Buenos Aires, Argentina E-mail:
[email protected]
Dedicated to Professor Rosa M. de Lederkremer on the occasion of her 70th anniversary
Abstract
Heteroaryl 1-thio-ß-D-galactofuranosides have been synthesized and evaluated as inhibitors of the exo-ß-D-galactofuranosidase from Penicillium fellutanum. 2-Pyridinethiol, 4-pyridinethiol, 1methylimidazole- 2-thiol, 5-methyl-1,3,4-thiadiazole-2-thiol, 2-pyrimidinethiol and 4,6-dimethyl2- pyrimidinethiol were employed as thiols, as such heteroaromatic aglycons are expected to display particular interactions with the active site of the enzyme. These thiols were condensed with per-O-benzoyl-D-galactofuranose, in the presence of SnCl4 or BF3.OEt2, followed by Odebenzoylation under mild conditions to afford the heteroaryl 1-thio-ß-D-galactofuranosides in high yields. The enzymatic assays showed that 4,6-dimethyl-2-pyrimidyl 1-thio-ß-Dgalactofuranoside was the best inhibitor (IC50 135 µM), considerable more potent than the analogue lacking the methyl groups in the aglycon moiety.
Keywords: Galactofuranose, galactofuranosidase inhibitors, heteroaryl 1-thio-ß-Dgalactofuranosides, glycobiology
Introduction
The synthesis of thioglycosides has received considerable attention because of their activity as inhibitors1 and inducers of glycosidases,2 and also because of their use as glycosyl donors in the convergent synthesis of oligosaccharides.3
Our laboratory has long been interested in the enzymes related to galactofuranose glycobiology, as galactofuranosyl residues are found in glycoconjugates of pathogenic microorganisms, such as the bacteria Mycobacterium tuberculosis and M. leprae,4,5 trypanosomatids like Trypanosoma cruzi and Leishmania,6-8 and fungi like Paracoccidioides
ISSN 1424-6376 Page 341 ©ARKAT USA, Inc
