| Title: |
A mild and atom-efficient four-component cascade strategy for the construction of biologically relevant 4-hydroxyquinolin-2(1H)-one derivatives |
| Authors: |
Dmitrii A. Grishin; Kseniia I. Sharkovskaia; Ilya G. Kolmakov; Daria A. Ipatova; Rostislav A. Petrov; Nikolai D. Dagaev; Dmitry A. Skvortsov; Maria G. Khrenova; Valeriy V. Andreychev; Sergei A. Evteev; Yan A. Ivanenkov; Roman L. Antipin; Olga А. Dontsova; Elena K. Beloglazkina |
| Source: |
Beilstein Journal of Organic Chemistry, Vol 22, Iss 1, Pp 244-256 (2026) |
| Publisher Information: |
Beilstein-Institut |
| Publication Year: |
2026 |
| Collection: |
Directory of Open Access Journals: DOAJ Articles |
| Subject Terms: |
antibacterial activity; 4-hydroxyquinolin-2(1h)-one; ʟ-proline catalysis; meldrum’s acid; michael addition; multicomponent reaction; Science; Organic chemistry; QD241-441 |
| Description: |
A mild and atom-economical four-component cascade reaction has been developed, enabling the efficient and selective synthesis of previously inaccessible 4-hydroxyquinolin-2(1H)-one derivatives. Utilizing readily available 6-halo-4-hydroxyquinolinones, aromatic aldehydes, Meldrum’s acid, and alcohols under ʟ-proline catalysis, the reaction proceeds via in situ formation of arylidene-substituted Meldrum acids followed by sequential Michael-type addition and subsequent cascade transformations. This versatile one-pot protocol delivers structurally diverse open-chain 3-arylpropanoate esters in moderate to good yields (46–69%), while cyclic pyranoquinolinones are formed under kinetically controlled conditions. Subsequent transformations afford isopropyl and cyclohexyl analogues via hydrolysis–esterification. A preliminary biological evaluation revealed low cytotoxicity and modest antibacterial activity against Escherichia coli ΔtolC strains. This sustainable synthetic approach constitutes the first direct access to scarcely explored open-chain quinolinone esters, expanding the medicinal chemistry toolbox with promising scaffolds for drug discovery. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://doi.org/10.3762/bjoc.22.18; https://doaj.org/toc/1860-5397; https://doaj.org/article/4fbddca0eb7d468d934bc9d645b55fcd |
| DOI: |
10.3762/bjoc.22.18 |
| Availability: |
https://doi.org/10.3762/bjoc.22.18; https://doaj.org/article/4fbddca0eb7d468d934bc9d645b55fcd |
| Accession Number: |
edsbas.4E2D1BCC |
| Database: |
BASE |