A Synthetic Approach for Evaluation of Cytosinediazonium Susceptibility


1 Faculty of Basic Sciences of Biotechnology, National Institute for Genetic Engineering and Biotechnology, Tehran, Iran

2 Department of Chemistry, Ferdowsi University of Mashhad, Mashhad, Iran

3 Department of Chemistry, Islamic Azad University, Mashhad branch, Mashhad, Iran


Reaction of a nucleobase with nitrosonium ion leads to its diazotization. Due to the instability,
the nucleobase-diazonium assumingly falls in dediazotization and successive ring opening
reactions. The resulting intermediate of the ring opening reaction is able to covalently cross-link
the opposite strands of DNA. To examine this assumption for cytosine, some 4-amino-5-cyano
pyrimidines were synthesized via [3+3] condensation of amidines with ethoxymethylenemalonitrile and successively converted to the corresponding 4-amino-5carboxyamido derivatives. These compounds were then exposed to nitrosonium ion under different conditions. Results of this study indicate that the diazonium of a 4-aminopyrimidine prefers deamination over the dediazotization. Therefore, the dediazotization and its successive ring-opening reactions of the pyrimidine cation would happen under some exceptional
conditions which deserve to be explored in more detailed studies. In view of the cytosine
chemistry and cytotoxicity of NO, the results are presented and discussed.