One-Step and Universal Strategy for the Synthesis of Hypermodified Uracil Phosphoramidites acp³U and cmnm⁵U

Hypermodified nucleosides have recently been at 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 for oligonucleotides bearing those hypermodified nucleobases led us to the development of a single-step synthesis of acp³U phosphoramidite, as acp³U has been recognized as an important molecule for the structural integrity of tRNA and native immunity. We also present a novel synthesis of cmnm⁵U phosphoramidite and its incorporation into an oligonucleotide from a highly versatile starting material, allowing a transformation into at least two other hypermodified nucleosides.