Synthesis of pseudouridine derivatives

There are over one hundred modified nucleosides found in natural RNAs. Among them, pseudouridine is the most common type of modification found abundantly in RNA. Derivatives such as 1-methylpseudouridine, 3-methyl pseudouridine, and 1-methyl-3-(3-amino-3-carboxypropyl)pseudouridine are also found in nature. The overall structural and functional effects of these modified nucleosides remain unclear. Therefore, the study of these modifications is very important. The first goal of this work was the synthesis of 13 C-pseudouridine as a tool to study structure and function of RNAs by NMR spectroscopy. The use of 13C labeling can help to assign the complex structure of RNAs. The second goal of this work was the synthesis of 1-methyl-3-(3-amino-3-carboxypropyl) pseudouridine, a pseudouridine derivative, and its corresponding phosphoramidite in order to construct hairpin RNAs containing the natural modification in human helix 31 of the small subunit ribosomal RNA. In the future, the modified RNAs will be used to investigate the structural consequences of modified nucleotides.