Towards One-Step and Universal Synthesis of Hypermodified Uracil Nucleosides: acp³U and cmnm⁵U

Hypermodified nucleosides have been recently in the center of scientific attention. They represent a unique group of nucleosides with an alternated structure, such as the addition of functional groups or amino acids. Their distinctive structures and positions in RNAs are crucial for the processes of translation and stability. High demand of oligonucleotides bearing those hypermodified nucleobases lead us to the development of a single step synthesis of acp 3 U phosphoramidite, as acp 3 U has been recognized as an important molecule for the structural integrity of tRNA and native immunity. We also present a novel synthesis of cmnm 5 U phosphoramidite and its incorporation into an oligonucleotide from a universal starting material, allowing a transformation into at least two other hypermodified nucleosides.