Synthesis of 1-(2'-Deoxy-ß-D-ribofuranosyl)-1H-imidazo[4,5-d]-pyridazine-4,7(5H,6H)-dione: A Potential Building Block for Antisense Applications

Abstract

Synthesis of the title compound,1-(2'-deoxy-b-D-ribofuranosyl)-1H-imidazo[4,5-d]pyridazine-4,7(5H,6H)-dione (1), is reported. It was synthesized in five steps, commencing with methyl 1-(b-D-ribofuranosyl)imidazo-4,5-dicarboxylate (2). The 3',5'-hydroxyl groups of 2 were protected with a bis-silylating agent to form 3, which was then converted into the corresponding 2'-thionocarbonate derivative 5. The reduction of the latter with tri-n-butyltin hydride (to form 6), followed by silyl deprotection with tetra-nbutylammonium fluoride, afforded 7. Treatment of the latter with hydrazine hydrate yielded the target nucleoside 1.

Keywords

• Synthesis
• Nucleoside Analogue
• Imidazo[4
• 5-d]pyridazine
• 2'-Deoxy Nucleoside Analogue