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3-Phenyl-5,6,7,8-tetrahydropyrimido[4,5-c]pyridazin-7-one As Nucleobase Substitute In DNA: Synthesis Of The 2′-deoxyribonucleoside, Cyclonucleoside Formation, And Base Pairing In Oligonucleotides
Published 2015 · Chemistry
Abstract A 5,6,7,8-tetrahydro derivative of 3-phenylpyrimido[4,5- c ]pyridazin-7-one 2′-deoxyribonucleoside ( 3 ) was designed as a dC mimic to form silver-mediated base pairs in DNA duplexes as reported for pyrrolo-dC 1 and imidazole-dC 2 . Compared to the fully aromatic molecule 4 , the nucleobase of 3 is hydrogenated with carbon-5 in the sp 3 hybridization state and an additional hydrogen atom located at nitrogen-8. Under aromatization conditions, nucleoside 3 undergoes cyclization to the 5,5′-cyclonucleoside 6 . The reaction is clearly related to the cyclization reported for 8-azapurine nucleosides. Nucleoside 3 was converted to the phosphoramidite 13 and was incorporated in oligonucleotides. In a distinct tautomeric state nucleoside 3 can be considered as a dT mimic while in another as dC derivative. Consequently, compound 3 forms a base pair with dA and dG. However, the desired silver-mediated base pair proposed for two identical nucleoside 3 residues facing each other could not be detected.