Regioselective alkylation reaction of the 2′-deoxyctidine with 9-aminomethyl derivatives of SN38

Abstract We present first evidence of a spontaneous alkylation of the 2′-deoxycytidine by potential topoisomerase I inhibitors from camptothecins family. The 7-ethyl-9-(N-morpholino)methyl-10-hydroxycamptothecin and the 7-ethyl-9-(N-pyrrolidinyl)methyl-10-hydoxycamptothecin regioselectively alkylate spontaneously an exo-cyclic nitrogen (N4) of the 2′- deoxycytidine. Product of the reaction has been confirmed using NMR techniques and DFT calculation of the carbon chemical shifts. This is the first evidence of spontaneous alkylation of DNA building block, the 2′-deoxycytidine, by this class of compounds, which are biologically active in vitro against several cancer cells, but tolerate normal cells.