Synthesis of heteroaryl 1-thio-ß-D-galactofuranosides and evaluation of their inhibitory activity towards a ß-D-galactofuranosidase

2006 ARKIVOC  
Dedicated to Professor Rosa M. de Lederkremer on the occasion of her 70 th anniversary Abstract Heteroaryl 1-thio-β-D-galactofuranosides have been synthesized and evaluated as inhibitors of the exo-β-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-dimethyl-2-pyrimidinethiol were employed as thiols, as such heteroaromatic aglycons are expected to display particular
more » ... 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-β-D-galactofuranosides in high yields. The enzymatic assays showed that 4,6-dimethyl-2-pyrimidyl 1-thio-β-Dgalactofuranoside was the best inhibitor (IC50 135 µM), considerable more potent than the analogue lacking the methyl groups in the aglycon moiety.
doi:10.3998/ark.5550190.0006.c27 fatcat:lmcf6e3j3vewlmrs4u6j4iou4i