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Updated: Jul 4, 2026

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Scalable Syntheses of Pseudouridine and N1-Methylpseudouridine
Yi Jiao1, Yiqiang Yang1,2, Bugao Zhou1,2
1State Key Laboratory of Analytical Chemistry for Life Science, Jiangsu Key Laboratory of Advanced Organic Materials, School of Chemistry, Nanjing University, Nanjing 210023, China.
Abstract:
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, N1-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.
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