中国科学院机构知识库网格
Chinese Academy of Sciences Institutional Repositories Grid
Weinreb Amide Approach to the Practical Synthesis of a Key Remdesivir Intermediate

文献类型:期刊论文

作者Xie, Yuanchao; Hu, Tianwen; Zhang, Yan; Wei, Daibao; Zheng, Wei; Zhu, Fuqiang; Tian, Guanghui; Aisa, Haji A; Shen, Jingshan
刊名The Journal of organic chemistry
出版日期2021
卷号86期号:7页码:5065-5072
ISSN号1520-6904
DOI10.1021/acs.joc.0c02986
英文摘要

Currently, remdesivir is the first and only FDA-approved antiviral drug for COVID-19 treatment. Adequate supplies of remdesivir are highly warranted to cope with this global public health crisis. Herein, we report a Weinreb amide approach for preparing the key intermediate of remdesivir in the glycosylation step where overaddition side reactions are eliminated. Starting from 2,3,5-tri-O-benzyl-d-ribonolactone, the preferred route consisting of three sequential steps (Weinreb amidation, O-TMS protection, and Grignard addition) enables a high-yield (65%) synthesis of this intermediate at a kilogram scale. In particular, the undesirable PhMgCl used in previous methods was successfully replaced by MeMgBr. This approach proved to be suitable for the scalable production of the key remdesivir intermediate.

源URL[http://ir.xjipc.cas.cn/handle/365002/7810]  
专题新疆理化技术研究所_省部共建新疆特有药用资源利用重点实验室
新疆理化技术研究所_资源化学研究室
作者单位1.Topharman Shanghai Co., Ltd., No. 388 Jialilue Road, Zhangjiang Hitech Park, Shanghai 201203, P. R. China
2.University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, P. R. China
3.Key Laboratory of Plant Resources and Chemistry in Arid Regions, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, South Beijing Road 40-1, Urumqi, Xinjiang 830011, P. R. China
4.Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Shanghai 201203, P. R. China
推荐引用方式
GB/T 7714
Xie, Yuanchao,Hu, Tianwen,Zhang, Yan,et al. Weinreb Amide Approach to the Practical Synthesis of a Key Remdesivir Intermediate[J]. The Journal of organic chemistry,2021,86(7):5065-5072.
APA Xie, Yuanchao.,Hu, Tianwen.,Zhang, Yan.,Wei, Daibao.,Zheng, Wei.,...&Shen, Jingshan.(2021).Weinreb Amide Approach to the Practical Synthesis of a Key Remdesivir Intermediate.The Journal of organic chemistry,86(7),5065-5072.
MLA Xie, Yuanchao,et al."Weinreb Amide Approach to the Practical Synthesis of a Key Remdesivir Intermediate".The Journal of organic chemistry 86.7(2021):5065-5072.

入库方式: OAI收割

来源:新疆理化技术研究所

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