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The sustainable synthesis of bioactive small molecules is crucial to the field of sports science and the development of nutritional strategies, using safe and effective methods to support performance and recovery. Pyrimidine derivatives, such as uridine and related nucleotides, are of particular interest because they have been shown to enhance cellular energy regeneration, reduce exercise-induced oxidative stress, and accelerate muscle and nerve repair. In this work, we report a covalent organic framework catalyst (Fe3O4@S-COF) that enables the high-performance synthesis of these bioactive compounds under mild aqueous conditions at room temperature. The Fe3O4@S-COF catalyst exhibits excellent stability, and it can be used repeatedly without a noticeable decrease in its effective catalytic activity. Importantly, the reactions can be carried out in water, thus avoiding toxic solvents/reagents, and the reaction is complete after only a few minutes of time (yields of over 90%–98%). Collectively, by providing an environmentally friendly and responsible route to bioactive molecules with known physiological impacts in sports contexts, the present work demonstrates how advances in green materials chemistry can provide valuable insights for life science research related to sports nutrition. An environmentally responsible synthesis and production mechanism supports a larger vision of sustainability, health, and performance improvement for athletes.

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