Synthesis and Selected Transformations of New 2‐Aminopyridine Derivatives Based on Furan‐2(5H)‐ones

• Published in: ChemistrySelect (Weinheim) Vol. 8; no. 30
• Main Authors: Hakobyan, Robert M., Shahkhatuni, Astghik A., Attaryan, Hovhannes S., Ayvazyan, Armen G., Melikyan, Gagik S.
• Format: Journal Article
• Language: English
• Published: 11.08.2023
• Subjects: 2-aminopyridine; butenolide; intramolecular cyclization; isoquinoline; proton sponge
• ISSN: 2365-6549; 2365-6549
• DOI: 10.1002/slct.202301183

Compounds with γ‐lactone fragments, as well as derivatives of 2‐aminopyridines and 2‐aminopyridons, are biologically active, and some of them are used as drugs. The condensed combination of γ‐lactones with 2‐aminopyridones, such as the natural alkaloid cerpegin, has a wider spectrum of biological activities. Here we combined γ‐lactone and 2‐aminopyridine derivatives into one molecule via a single bond. A series of such compounds were synthesized in high yields through the transformations of unsaturated furan‐2(5H)‐ones. Interestingly, only two of the obtained compounds underwent intermolecular cyclization and led to new isoquinoline derivatives with skeletons similar to the “proton sponges”. Two biologically active fragments, γ‐lactone and 2‐aminopyridine, were combined in one molecule via a single bond. After a three‐step synthesis we obtain a series of butenolides with various substituted pyridines in the 3rd position of a lactone ring. Compounds with a primary amino substituent on the pyridine ring undergo intramolecular cyclization and lead to new isoquinoline derivatives with skeletons similar to the “proton sponges”.