Direct and Catalytic C-Glycosylation of Arenes: Expeditious Synthesis of the Remdesivir Nucleoside.
Angew Chem Int Ed Engl
; 61(11): e202114619, 2022 03 07.
Article
in English
| MEDLINE | ID: covidwho-1544209
ABSTRACT
Since early 2020, scientists have strived to find an effective solution to fight SARS-CoV-2, in particular by developing reliable vaccines that inhibit the spread of the disease and repurposing drugs for combatting its effects on the human body. The antiviral prodrug Remdesivir is still the most widely used therapeutic during the early stages of the infection. However, the current synthetic routes rely on the use of protecting groups, air-sensitive reagents, and cryogenic conditions, thus impeding a cost-efficient supply to patients. We have, therefore, focused on the development of a straightforward, direct addition of (hetero)arenes to unprotected sugars. Here we report a silylium-catalyzed and completely stereoselective C-glycosylation that initially yields the open-chain polyols, which can be selectively cyclized to provide either the kinetic α-furanose or the thermodynamically favored ß-anomer. The method significantly expedites the synthesis of Remdesivir precursor GS-441524 after a subsequent Mn-catalyzed C-H oxidation and deoxycyanation.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Antiviral Agents
/
Adenosine
/
Adenosine Monophosphate
/
Alanine
/
Nucleosides
Type of study:
Experimental Studies
/
Randomized controlled trials
Topics:
Vaccines
Limits:
Humans
Language:
English
Journal:
Angew Chem Int Ed Engl
Year:
2022
Document Type:
Article
Affiliation country:
Anie.202114619
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