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

Abstract

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.

• Authors: Amarender Manchoju, Renaud Zelli, Gang Wang, Carla Eymard, Adrian Oo, Mona Nemer, Michel Prévost, Baek Kim, Yvan Guindon
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 27 Issue 2 (Jan 17 2022) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 35056878 (Publication Type: Journal Article)

Chemical References

• Antiviral Agents
• Heterocyclic Compounds, 4 or More Rings
• Nucleotides
• Carbon
• RNA-Dependent RNA Polymerase

Topics

• Antiviral Agents (chemical synthesis, chemistry, pharmacology)
• Carbon (chemistry)
• Heterocyclic Compounds, 4 or More Rings (chemical synthesis, chemistry, pharmacology)
• Nucleotides (chemical synthesis, chemistry, pharmacology)
• RNA-Dependent RNA Polymerase (antagonists & inhibitors)
• SARS-CoV-2 (drug effects, enzymology)
• Stereoisomerism