A Convenient Synthesis of the Cytidyl 3'-Terminal Monomer for Solid-Phase Synthesis of RNG Oligonucleotides

Synthetic oligonucleotides are widely researched as potential therapeutic agents, as the chemical modification of nucleotides may increase their ability to silence genes at both the transcriptional and translational level. Replacing the phosphodiester backbone of RNA with positively charged guanidinium linkages has been shown to enable RNA oligomers to overcome electrostatic repulsion and bind double-stranded DNA in a triplex with high affinity. Ribonucleotide monomers with the ability to form guanidinium linkages have been synthesized for the generation of ribooligonucleotides with guanidinium linkages (RNGs) through solid-phase synthesis. We report herein an efficient method for the synthesis of N⁴-Benzoyl-2’-O-(tert-butyldimethylsilyl)-5’-N-(4-monomethoxytritylamino)-3’-O-succinyl-5’-deoxycytidine, a new monomer required for the solid-phase synthesis of cytidyl RNG oligonucleotides.