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

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 functiona...

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Vydané v:	Molecules (Basel, Switzerland) Ročník 27; číslo 2; s. 564
Hlavní autori:	Manchoju, Amarender, Zelli, Renaud, Wang, Gang, Eymard, Carla, Oo, Adrian, Nemer, Mona, Prévost, Michel, Kim, Baek, Guindon, Yvan
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Switzerland MDPI AG 17.01.2022 MDPI
Predmet:	Alcohol Antiviral Agents - chemical synthesis Antiviral Agents - chemistry Antiviral Agents - pharmacology Carbon Carbon - chemistry Coronaviruses COVID-19 Enzymes epoxidation Heterocyclic Compounds, 4 or More Rings - chemical synthesis Heterocyclic Compounds, 4 or More Rings - chemistry Heterocyclic Compounds, 4 or More Rings - pharmacology Laboratories nucleoside analogues Nucleotides - chemical synthesis Nucleotides - chemistry Nucleotides - pharmacology Phosphorylation quaternary stereocenter RdRp RNA polymerase RNA-Dependent RNA Polymerase - antagonists & inhibitors SARS-CoV-2 SARS-CoV-2 - drug effects SARS-CoV-2 - enzymology Severe acute respiratory syndrome coronavirus 2 Stereoisomerism Viruses COVID-19 SARS-CoV-2 epoxidation RdRp nucleoside analogues quaternary stereocenter glycosylation triphosphorylation
ISSN:	1420-3049, 1420-3049
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Popis
Shrnutí:	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.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 This paper is dedicated to Professor Stephen Hanessian-a mentor, colleague and friend.
ISSN:	1420-3049 1420-3049
DOI:	10.3390/molecules27020564