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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
- 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.
- Subjects :
- Proteases
Glutamine
medicine.medical_treatment
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Antiviral Agents
01 natural sciences
03 medical and health sciences
chemistry.chemical_compound
Hydrogenolysis
medicine
Humans
Protease Inhibitors
Coronavirus 3C Proteases
030304 developmental biology
chemistry.chemical_classification
0303 health sciences
Protease
SARS-CoV-2
010405 organic chemistry
Organic Chemistry
COVID-19
Note
Oxime
Combinatorial chemistry
0104 chemical sciences
Amino acid
chemistry
Pharmacophore
Subjects
Details
- ISSN :
- 15206904 and 00223263
- Volume :
- 86
- Database :
- OpenAIRE
- Journal :
- The Journal of Organic Chemistry
- Accession number :
- edsair.doi.dedup.....15796783896a2db67c1af3811377aae0