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Process Chemistry in Antiviral Research

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Abstract

This article reviews antiviral therapies that have been approved for human use during the last decade, with a focus on the process chemistry that enabled access to these important drugs. In particular, process chemistry highlights from the practical syntheses of the HCV drugs sofosbuvir (Gilead), grazoprevir (Merck), and elbasvir (Merck), the HIV therapy darunavir (Tibotec) and the influenza treatment peramivir (BioCryst) are presented.

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Notes

  1. The situation may be actually slightly more complex because the phosphoramidate hydrolyzes to leave the 5′-phosphate, which avoids the need for biological mono-phosphorylation of the 5′-alcohol, on the pathway towards triphosphate formation.

  2. Employed a similar processes developed by Gilead Sciences, lactone 11-OBn was converted to 29 in 25% overall yield.

  3. The chlorides in the chlorophosphates 30a and 30b are replaced by pentafluorophenol due to the instability of the chlorophosphate towards isolation/upgrade.

  4. Intermediate 48 can be sourced.

  5. Alternate, stereoselective approaches were ultimately developed by Merck Research Laboratories and will be the subject of future publications.

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Authors and Affiliations

  1. Department of Process Chemistry, Merck and Co., Inc., PO Box 2000, Rahway, NJ, 07065, USA

    Yong-Li Zhong, Nobuyoshi Yasuda, Hongming Li, Mark McLaughlin & David Tschaen

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  1. Yong-Li Zhong
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  2. Nobuyoshi Yasuda
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  3. Hongming Li
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  4. Mark McLaughlin
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  5. David Tschaen
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Correspondence to Yong-Li Zhong.

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This article is part of the Topical Collection “Antiviral Drug Research”; edited by Guangxin Liang, Zheng Yin.

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Zhong, YL., Yasuda, N., Li, H. et al. Process Chemistry in Antiviral Research. Top Curr Chem (Z) 374, 77 (2016). https://doi.org/10.1007/s41061-016-0076-5

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