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Improved Synthesis of a Cyclic Glutamine Analogue Used in Antiviral Agents Targeting 3C and 3CL Proteases Including SARS-CoV-2 Mpro

Authors :
John C. Vederas
Wayne Vuong
Source :
The Journal of Organic Chemistry
Publication Year :
2021
Publisher :
American Chemical Society (ACS), 2021.

Abstract

An intermediate in the synthesis of numerous antiviral protease inhibitors is the glutamine analogue, (3S)-pyrrolid-2-one-3-yl-l-alanine. Preparations of compounds based on this pharmacophore are hindered by the lack of a reliably high yielding synthesis of protected forms of this amino acid. We describe an improved scalable route with readily available reagents and facile purification. This methodology employs γ-allylation of dimethyl N-BocGlu, further Boc N-protection, OsO4-periodate oxidation, O-Me oxime formation, and RaNi-catalyzed hydrogenolysis with concomitant cyclization under basic conditions.

Details

ISSN :
15206904 and 00223263
Volume :
86
Database :
OpenAIRE
Journal :
The Journal of Organic Chemistry
Accession number :
edsair.doi.dedup.....15796783896a2db67c1af3811377aae0