Pseudouridine ( Ψ ) is a naturally occurring C -nucleoside featuring a C–C glycosidic bond. When incorporated into mRNA, it confers reduced immunogenicity and enhanced translational efficiency, driving advances in mRNA vaccine research. Its derivative, N 1 -methylpseudouridine ( m1Ψ ), played a pivotal role in the successful deployment of COVID-19 mRNA vaccines. Herein, we report two synthetic routes for Ψ and m1Ψ . The first enables gram-scale laboratory syntheses of both C -nucleosides. The second, optimized to address specific process challenges, facilitates kilogram-scale industrial production. These developments are expected to accelerate the application of these modified nucleosides in next-generation mRNA vaccine development.
Jiao et al. (Thu,) studied this question.