Synthesis of 1-(2-O-Methyl-ß-D-ribofuranosyl)-1H-imidazo45-dpyridazine-47(5H6H)-dione: An Attractive Building Block for Antisense and Triple-helical Applications

摘要

Synthesis of the title compound,1-(2'-O-methyl-ß-D-ribofuranosyl)-1H-imidazo-[4,5-d]pyridazine-4,7(5H,6H)-dione (>1), is reported. It was synthesized in four steps, starting from methyl 1-(ß-D-ribofuranosyl)imidazo-4,5-dicarboxylate (>2). The 3',5'-hydroxyl groups of >2 was protected with a bis-silylating agent to form >3, which was then methylated to form the corresponding 2'-O-methyl derivative >5. The silyl deprotection of the latter (to form >6), followed by treatment with hydrazine afforded the target nucleoside >1. The reported nucleoside has potentially beneficial applications in biomedicine based on antisense and triple-helical nucleic acid technologies.