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

MARINO, MARÍA CARLA; MARIÑO KARINA

Arkivoc

Año: 2005 vol. 12 p. 341 - 351

1424-6376

Heteroaryl 1-thio-b-D-galactofuranosides have been synthesized and evaluated as inhibitors of the exo-b-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 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 O-debenzoylation under mild conditions to afford the heteroaryl 1-thio-b-D-galactofuranosides in high yields. The enzymatic assays showed that 4,6-dimethyl-2-pyrimidyl 1-thio-b-D-galactofuranoside was the best inhibitor (IC50135 mM), considerable more potent than the analogue lacking the methyl groups in the aglycon moiety.