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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.

SUBMITTER: Manchoju A

PROVIDER: S-EPMC8781509 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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

Manchoju Amarender A Zelli Renaud R Wang Gang G Eymard Carla C Oo Adrian A Nemer Mona M Prévost Michel M Kim Baek B Guindon Yvan Y

Molecules (Basel, Switzerland) 20220117 2

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 <i>N</i>-glycosylations and re ...[more]

PMID: 35056878

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