Effective syntheses of 2′,4′-BNANC monomers bearing adenine, guanine, thymine, and 5-methylcytosine, and the properties of oligonucleotides fully modified with 2′,4′-BNANC

[Display omitted] •2′-O,4′-C-aminomethylene bridged nucleic acid (2′,4′-BNANC) monomers were prepared.•These monomers contained guanine, adenine, thymine, or 5-methylcytosine.•The key reaction was a transglycosylation reaction for the purine-bearing monomers.•An improved route was also reported toward the pyrimidine-bearing monomers.•Duplexes of the fully-2′,4′-BNANC-modified oligonucleotides were thermally stable. We efficiently synthesized 2′-O,4′-C-aminomethylene-bridged nucleic acid (2′,4′-BNANC) monomers bearing the four nucleobases, guanine, adenine, thymine, and 5-methylcytosine and incorporated these monomers into oligonucleotides. Initially, we carried out the transglycosylation reaction on several 2′-O-substituted 5-methyluridines to evaluate the effects of 2′-substitutions on this reaction. Under the optimized conditions, purine nucleobases were successfully introduced, and 2′,4′-BNANC monomers bearing adenine or guanine were obtained over several steps. In addition, the improved synthesis of the 2′,4′-BNANC monomers bearing thymine or 5-methylcytosine was also achieved. The obtained 2′,4′-BNANC monomers were subsequently incorporated into oligonucleotides and the duplex-forming abilities of the modified oligonucleotides were investigated. Duplexes containing 2′,4′-BNANC monomers in both or either strands were found to possess excellent thermal stabilities.