Nucleotide Analogues Bearing a C2′ or C3′-Stereogenic All-Carbon Quaternary Center as SARS-CoV-2 RdRp Inhibitors

被引：5

作者：

Manchoju, Amarender ^{[1
]}

Zelli, Renaud ^{[1
]}

Wang, Gang ^{[1
]}

Eymard, Carla ^{[1
]}

Oo, Adrian ^{[2
]}

Nemer, Mona ^{[3
]}

Prevost, Michel ^{[1
]}

Kim, Baek ^{[2
,4
]}

Guindon, Yvan ^{[1
,3
,5
]}

机构：

[1] Inst Recherches Clin Montreal, Bioorgan Chem Lab, Montreal, PQ H2W 1R7, Canada

[2] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA 30322 USA

[3] Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON K1N 6N5, Canada

[4] Childrens Hlthcare Atlanta, Atlanta, GA 30322 USA

[5] Univ Montreal, Dept Chem, Montreal, PQ H3C 3J7, Canada

来源：

MOLECULES | 2022年 / 27卷 / 02期

基金：

加拿大自然科学与工程研究理事会; 加拿大健康研究院;

关键词：

SARS-CoV-2; COVID-19; RdRp; quaternary stereocenter; nucleoside analogues; epoxidation; glycosylation; triphosphorylation; NUCLEOSIDE; EPOXIDATION; DISCOVERY; ADDITIONS;

D O I：

10.3390/molecules27020564

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The design of novel nucleoside triphosphate (NTP) analogues bearing an all-carbon quaternary center at C2 ' or C3 ' is described. The construction of this all-carbon stereogenic center involves the use of an intramoleculer photoredox-catalyzed reaction. The nucleoside analogues (NA) hydroxyl functional group at C2 ' was generated by diastereoselective epoxidation. In addition, highly enantioselective and diastereoselective Mukaiyama aldol reactions, diastereoselective N-glycosylations and regioselective triphosphorylation reactions were employed to synthesize the novel NTPs. Two of these compounds are inhibitors of the RNA-dependent RNA polymerase (RdRp) of SARS-CoV-2, the causal virus of COVID-19.

引用

页数：25

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