Post-synthetic transamination at position N4 of cytosine in oligonucleotides assembled with routinely used phosphoramidites

The commercially available and cheap nucleotide phosphoramidites are routinely used for the oligonucleotide (ODN) assembly. T, isobutyryl-dG (^iBudG), benzoyl-dA (^BzdA), acetyl-dC (^AcdC) and benzoyl-dC (^BzdC) derivatives are sufficient to produce orthogonally protected ODNs. Clean and efficient (ca. 30%–70% yield) post-synthetic amination of an ODN assembled with such phosphoramidites was selectively achieved at the N4 position of a singly introduced ^BzdC. Such a method represents a novel and cheap strategy for the user-friendly post-modification of oligonucleotides at the internal position.