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. 2020 Nov 16;59(47):20814-20819.
doi: 10.1002/anie.202011527. Epub 2020 Oct 8.

Catalytic Asymmetric Synthesis of the anti-COVID-19 Drug Remdesivir

Mo Wang  1   2 , Lu Zhang  2 , Xiaohong Huo  1 , Zhenfeng Zhang  2 , Qianjia Yuan  1 , Panpan Li  1 , Jianzhong Chen  1 , Yashi Zou  1 , Zhengxing Wu  1 , Wanbin Zhang  1   2
Affiliations

Catalytic Asymmetric Synthesis of the anti-COVID-19 Drug Remdesivir

Mo Wang et al. Angew Chem Int Ed Engl. .

Abstract

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.

Keywords: asymmetric catalysis; drug design; organocatalysis; phosphoramidates; synthetic methods.

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References

    1. None
    1. M. L. Holshue, C. DeBolt, S. Lindquist, K. H. Lofy, J. Wiesman, H. Bruce, C. Spitters, K. Ericson, S. Wilkerson, A. Tural, G. Diaz, A. Cohn, L. Fox, A. Patel, S. I. Gerber, L. Kim, S. X. Tong, X. Y. Lu, S. Lindstrom, M. A. Pallansch, W. C. Weldon, H. M. Biggs, T. M. Uyeki, S. K. Pillai, Washington State2019-nCoV Case Investigation Team, N. Engl. J. Med. 2020, 382, 929-936;
    1. An Open Letter from Daniel O'Day, Chairman & CEO, Gilead Sciences, Daniel O'Day-June 22, 2020.
    1. US Food and Drug Administration. Remdesivir EUA letter of authorization, 2020. Available: https://www.fda.gov/media/137564/ download [Accessed 1 May 2020].
    1. An Open Letter from Daniel O'Day, Chairman & CEO, Gilead Sciences on June 29, 2020: https://www.gilead.com/stories/articles/an-open-letter-from-daniel-oday-....

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