Synthesis of Metal-Chelating Deoxycytidine-Analogue Phosphoramidites for the Automatic Synthesis of Labelled Oligonucleotides

The new deoxycytidine (dC) analogue phosphoramidites 1-3 were synthesized, which bear an ethylenediaminetetraacetic acid triethyl ester [EDTA(OEt)(3)] attached to the exocyclic amino group through either a cyclic-C-6, a C-2, or a linear-C-6 tether. By this way, the chelating base dC-EDTA can be inserted, by automatic synthesis, in a site-specific manner into oligodeoxynucleotides (ODNs), in place of any dC along the sequence, and can be thus exploited, for example, for footprinting experiments. Furthermore, the analogue phosphoramidite 4, bearing a diethylenetriaminepentaacetic acid tetraethyl ester [DTPA(OEt)(4)] attached through the cyclic-C-6 tether was also prepared. The possibility of insertion of 1-4 into ODNs was verified.