Catalytic Asymmetric Synthesis of the anti-COVID-19 Drug Remdesivir.
Mo WangLu ZhangXiaohong HuoZhenfeng ZhangQianjia YuanPanpan LiJianzhong ChenYashi ZouZhengxing WuWanbin ZhangPublished in: Angewandte Chemie (International ed. in English) (2020)
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.
Keyphrases
- ionic liquid
- room temperature
- coronavirus disease
- sars cov
- highly efficient
- reduced graphene oxide
- carbon dioxide
- metal organic framework
- solid state
- visible light
- heavy metals
- wastewater treatment
- adverse drug
- gram negative
- respiratory syndrome coronavirus
- crystal structure
- drug induced
- electron transfer
- multidrug resistant