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The catalytic asymmetric synthesis of the anti‐COVID‐19 drug Remdesivir has been realized by the coupling of the P‐racemic phosphoryl chloride with protected nucleoside GS441524. The chiral bicyclic imidazole catalyst used is crucial for the dynamic kinetic asymmetric transformation (DyKAT) to proceed smoothly with high reactivity and excellent stereoselectivity (96 % conv. 22:1 SP:RP). Mechanistic studies showed that this DyKAT is a first‐order visual kinetic reaction dependent on the catalyst concentration. The unique chiral bicyclic imidazole skeleton and carbamate substituent of the catalyst are both required for the racemization process, involving the phosphoryl chloride, and subsequent stereodiscriminating step. A 10 gram scale reaction was also conducted with comparably excellent results, showing its potential for industrial application. [ABSTRACT FROM AUTHOR]

Frontispiz: Catalytic Asymmetric Synthesis of the anti-COVID-19 Drug Remdesivir Keywords: asymmetric catalysis; drug design; organocatalysis; phosphoramidates; synthetic methods EN asymmetric catalysis drug design organocatalysis phosphoramidates synthetic methods 1 1 1 11/11/20 20201116 NES 201116 B Asymmetrische Synthese b Die erste katalytische asymmetrische Synthese von Remdesivir durch die Kupplung von P-racemischem Phosphorylchlorid mit dem geschützten Nukleosid GS441524 wird von W. Zhang et al. in der Zuschrift auf S. 21000 vorgestellt. Asymmetric catalysis, drug design, organocatalysis, phosphoramidates, synthetic methods. [Extracted from the article]