Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

Yordanka Mollova-Sapundzhieva; Plamen Angelov; Danail Georgiev; Pavel Yanev

doi:10.3762/bjoc.19.132

Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

Beilstein J Org Chem. 2023 Nov 23:19:1804-1810. doi: 10.3762/bjoc.19.132. eCollection 2023.

Authors

Yordanka Mollova-Sapundzhieva¹, Plamen Angelov¹, Danail Georgiev², Pavel Yanev¹

Affiliations

¹ Department of Organic Chemistry, University of Plovdiv Paisii Hilendarski, 24 Tsar Asen Str., 4000 Plovdiv, Bulgaria.
² Department of Biochemistry and Microbiology, University of Plovdiv Paisii Hilendarski, 24 Tsar Asen Str., 4000 Plovdiv, Bulgaria.

Abstract

β-Keto amides were used as convenient precursors to both 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides. The utility of this approach is demonstrated with the synthesis of fourteen novel and four known quinolone derivatives, including natural products of microbial origin such as HHQ and its C₅-congener. Two compounds with high activity against S. aureus have been identified among the newly obtained quinolones, with MICs ≤ 3.12 and ≤ 6.25 µg/mL, respectively.

Keywords: 4-quinolones; antibacterial; enaminones; quorum sensing; β-keto amides.

Grants and funding

This research was funded by the Bulgarian National Science Fund, grant number KP-06-N59/14 and the Royal Society of Chemistry (UK), grant number R21-2062713611. Pavel Yanev acknowledges a postdoctoral grant from the National Program of Ministry of Education and Science “Young Scientists and Postdoctoral Students – 2 - 2022”.