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 and
• Pavel Yanev

Beilstein J. Org. Chem. 2023, 19, 1804–1810, doi:10.3762/bjoc.19.132

• ., 4000 Plovdiv, Bulgaria 10.3762/bjoc.19.132 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: antibacterial; β-keto amides; enaminones; 4-quinolones; quorum

• sensing; Introduction Among the vast number of biologically active quinoline derivatives [1][2], the subclass of 4-quinolones (also referred to as 4-oxo-1,4-dihydroquinolines, quinolin-4(1H)-ones, or 4-hydroxyquinolines) is of great importance with its rich variety of bioactive compounds. Perhaps the

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• -2,3-dihydro-4-quinolones 99 were obtained in good yields of up to 95% and good ee (58–72%) (Table 22) [61]. 2. Covalent-bonding organocatalysis of aza-Michael reactions This category of organocatalysts includes N-heterocyclic carbenes and pyrrolidine derivatives. 2.1 Catalysis by N-heterocyclic

• acids have been shown to catalyze the reactions via single or double hydrogen bonding [57][58]. Saito et al. accomplished the chiral phosphoric acid-catalyzed intramolecular aza-Michael addition reaction of N-unprotected 2-aminophenyl vinyl ketones 90 to obtain chiral 2-substituted 2,3-dihydro-4

• -quinolones 92 in very good yields (67–95%) with high ee (82–97%) (Table 20) [59]. Following a similar approach, Yang et al. reported asymmetric aza-Michael additions of anilines 94 to β-nitrostyrenes 93 using a chiral binol-derived phosphoric acid diester catalyst (cat. 95). They succeeded in preparing β

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• acids to 3-methyl-2-cyclohexanone catalysed by L9/Pd(TFA)2 [49]. Addition reaction of phenylboronic acid to various enones, lactones, and chromones catalysed by L9/Pd(TFA)2 [48][51]. Addition reactions of arylboronic acids to substituted chromones and N-Cbz-4-quinolones catalysed by L9/Pd(TFA)2 [51

Two new 2-alkylquinolones, inhibitory to the fish skin ulcer pathogen Tenacibaculum maritimum, produced by a rhizobacterium of the genus Burkholderia sp.

• Dandan Li,
• Naoya Oku,
• Atsumi Hasada,
• Masafumi Shimizu and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2018, 14, 1446–1451, doi:10.3762/bjoc.14.122

• -1 Yanagido, Gifu 501-1193, Japan 10.3762/bjoc.14.122 Abstract Exploration of rhizobacteria of the genus Burkholderia as an under-tapped resource of bioactive molecules resulted in the isolation of two new antimicrobial 2-alkyl-4-quinolones. (E)-2-(Hept-2-en-1-yl)quinolin-4(1H)-one (1) and (E)-2

• [21][22][23][24][25], Gram-positive [26][27] and Gram-negative bacteria [28][29][30], and a marine sponge [31]. Among a variety of substituted 4-quinolones, 2-alkyl-4-quinolones are the most common core in antibiotics [32], which were originally discovered as anti-anthrax metabolites produced by

• revealed 5-lipoxygenase inhibitory activity [33], plant-growth promoting activity [32][34], and IGF-dependent cell-specific cytotoxicity [14]. A recent metabolomic analysis using LC–MS verified the presence of more than 50 2-alkyl-4-quinolones [35], most of which remain chemically and biologically

Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa

• Michaela Prothiwa,
• Dávid Szamosvári,
• Sandra Glasmacher and
• Thomas Böttcher

Beilstein J. Org. Chem. 2016, 12, 2784–2792, doi:10.3762/bjoc.12.277

• . This simple signaling strategy thus regulates bacterial behaviour in dependence of population density. One of these quorum sensing systems, the pqs system, uses 2-alkyl-4-quinolones (AQs) as signals of which the Pseudomonas quinolone signal (PQS) and its biosynthetic precursor 2-heptyl-4-quinolone (HHQ

• combination, our probes and their inhibitors represent a valuable toolkit for investigating this important virulence-related enzyme. Quinolone signals of Pseudomonas aeruginosa. A) Structures of HHQ and PQS. B) Proposed mechanism for the synthesis of 2-alkyl-4-quinolones [12][13][14]. Synthesis of

The Elbs and Boyland- Sims peroxydisulfate oxidations

• E. J. Behrman

Beilstein J. Org. Chem. 2006, 2, No. 22, doi:10.1186/1860-5397-2-22

• -reaction and so increases the yield of the expected Elbs product, orotic acid 5-sulfate. Quinolones are another interesting case: 4-quinolones give reasonable yields of the expected 3-substitution products whereas 2-quinolones do not. [6] An explanation has been suggested which concerns the stability of