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The Syntheses of Pyrimido‐pyridazinone and Pyrrolidino‐pyrimidinone 2′‐Deoxynucleoside Derivatives
Author(s) -
Loakes David,
Guo MaoJun,
Yang JiChun,
Brown Daniel M.
Publication year - 2000
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(20000809)83:8<1693::aid-hlca1693>3.0.co;2-e
Subject(s) - bicyclic molecule , chemistry , tautomer , derivative (finance) , stereochemistry , nucleoside , pyrimidine , combinatorial chemistry , ring (chemistry) , nucleic acid , organic chemistry , biochemistry , financial economics , economics
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 N 4 ‐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.