The Syntheses of Pyrimido-pyridazinone and Pyrrolidino-pyrimidinone 2′-Deoxynucleoside Derivatives

Abstract

Nucleosides that have ambivalent tautomeric properties have value in a variety of nucleic-acid hybridisation applications and as mutagenic agents. We describe here synthetic studies directed to stable derivatives based on N4-aminocytosine. Treatment of the 5-(chloroethyl)-4-(triazol-1-yl)pyrimidine-nucleoside derivative 1 with benzylhydrazine leads to the formation of the 6,6-bicyclic pyrimido-pyridazin-7-one 6, in addition to the 5,6-bicyclic derivative 7. The 6,6-bicyclic benzyl derivative 6 was converted to its 5′-triphosphate for studies with DNA polymerases. Reaction of the triazole 1 with hydrazine, followed by acetylation, led to the desired acetylated 6,6-bicyclic derivative 12. However, the latter compound undergoes acyl migration followed by ring contraction to the 5,6-bicyclic compound 13 on treatment with base.