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

MARIÑO, KARINA; MARINO, CARLA

Arkivoc

Arkat USA

Año: 2005 vol. 2005 p. 341 - 351

1424-6376

Heteroaryl 1-thio-beta-D-galactofuranosides have been synthesized and evaluated as inhibitors ofthe exo-beta-D-galactofuranosidase from Penicillium fellutanum. 2-Pyridinethiol, 4-pyridinethiol, 1-methylimidazole-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 todisplay particular interactions with the active site of the enzyme. These thiols were condensedwith per-O-benzoyl-D-galactofuranose, in the presence of SnCl4 or BF3.OEt2, followed by O-debenzoylation under mild conditions to afford the heteroaryl 1-thio-beta-D-galactofuranosides in high yields. The enzymatic assays showed that 4,6-dimethyl-2-pyrimidyl 1-thio-beta-galactofuranoside was the best inhibitor (IC50 135 uM), considerable more potent than theanalogue lacking the methyl groups in the aglycon moiety.