Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• ][74]. It was furthermore cytotoxic against A549, MG-63, and SMMC-7721 cell lines (IC50 values of 1.47, 2.11, and 7.34 μg/mL, respectively) [123]. It showed antibacterial activity against Staphylococcus aureus including methicillin-resistant S. aureus (MRSA) and quinolone-resistant S. aureus (QRSA

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• the partner might be investigated offering numerous possibilities for the assembly of heterocycles. As early as 1988, Tabaković and Gunić examined the anodic oxidation of aldehyde-derived NH-arylhydrazones 44 in the presence of pyridine and (iso)quinolone derivatives 45 in acetonitrile

Synthesis and optical properties of bis- and tris-alkynyl-2-trifluoromethylquinolines

• Stefan Jopp,
• Franziska Spruner von Mertz,
• Peter Ehlers,
• Alexander Villinger and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1246–1255, doi:10.3762/bjoc.20.107

• is applied as antimalarial agent and furthermore as a bitter flavour component. Mefloquin [5] and ciprofloxacin [6], on the other hand, are synthetic compounds containing a fluorinated quinoline and quinolone core structure and are used as antimalarial and antibacterial agents, respectively (Figure 1

• -bromoaniline (1a) and ethyl trifluoroacetoacetate (2), adapting a known procedure from Schlosser and Marull (Scheme 1) [17]. The cyclization of 1a with 2a chemoselectively afforded 8-bromo-2-trifluoromethyl-4-quinolone (3) rather than 8-bromo-4-trifluoromethyl-2-quinolone. Bromination of 3 with phosphoryl

• electronic push–pull interaction of the thiophene and the quinoline moieties via the alkyne. Finally, we focussed on the synthesis of tris-alkynylated quinolines starting from 3,4,8-tribromo-2-(trifluoromethyl)quinoline (11). Starting material 11 was synthesized in very good yield from quinolone 3 by

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

• avicennae [18]. Inhibition of hepatitis C virus replication by 2-nonyl-4-quinolone, isolated from Ruta angustifolia leaves, has also been reported [19]. Another significant group of natural 4-quinolones are those of microbial origin. The function of these compounds in the microbial world is a matter of

• extensively studied is 2-heptyl-4-quinolone (HHQ) and its oxygenated derivatives 2-heptyl-3-hydroxy-4-quionolone (PQS) and 4-hydroxy-2-heptylquinoline-N-oxide (HQNO) [27][36][37][38]. Considering the importance of 4-quinolones as potential drugs and biological probes, it is not surprising that the development

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• chlorinated product 21 was detected, which with POCl3 gave the cyclized product 22. Also, the synthesis of benzo[b]thieno[2,3-c]quinolone 24 as an anticancer molecule was demonstrated in this approach (Scheme 13). An intermolecular sulfenoamination of alkenes 9 with sulfonamides 25 as the nitrogen source and

Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme

• Josipa Matić,
• Tana Tandarić,
• Marijana Radić Stojković,
• Filip Šupljika,
• Zrinka Karačić,
• Ana Tomašić Paić,
• Lucija Horvat,
• Robert Vianello and
• Lidija-Marija Tumir

Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40

• ). Phen-Py-2 also showed a shoulder at 480 nm (besides the main emission signal at 400 nm) which could be attributed to the excimer formation (Figure S2, Supporting Information File 1). A similar new red-shifted emission band was noticed for other exciplex examples: pyrene–guanine [10] pyrene–quinolone

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• constructed from the corresponding rhenium complexes by using [99mTc(CO)3(H2O)3]+ at pH 7.4 and 90 °C temperature. Santos et al. [39] reported in 2008 the synthesis of CuAAC-ensembled 1,2,3-triazole-linked porphyrin-quinolone conjugates 70a–e by considering the biological significance of both the porphyrin

• and quinolone groups. The click reaction was performed between alkyne-substituted porphyrins 68a–e and 6-azidoquinolone 69 for the preparation of mono-, di-, tri-, and tetratriazoloporphyrin-quinolone conjugates 70a–e in 53–93% yields (Scheme 13). In the following reports, Leroy-Lhez et al. [40] used

• . The CuAAC click reaction has been shown to bind a variety of chromophores bearing azide or alkyne groups to the porphyrin periphery, including coumarin, xanthone, DNA, ferrocene, corrole, fluorescein, carborane, BODIPY, graphene, carboline, fullerene, NDI, β-cyclodextrin, cholic acid, quinolone, etc

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• studies, one of us (M. R. E. A.) felt intrigued by the potential of chemical hybridization of cholesterol through simple connections of pharmacophores including sugars, chalcones, quinolone, theophylline, and ferrocene using click chemistry [9][10][11]. Following this strategy, cholesterol was

First total synthesis of hoshinoamide A

• Haipin Zhou,
• Zihan Rui,
• Yiming Yang,
• Shengtao Xu,
• Yutian Shao and
• Long Liu

Beilstein J. Org. Chem. 2021, 17, 2924–2931, doi:10.3762/bjoc.17.201

• Plasmodium, which seriously threatens human life and health [1]. Half of the world's population is at the risk of malaria, causing 200 million new infections and killing hundreds of thousands of people each year [2]. Current medicines for malaria include quinolone [3][4], folic acid antagonist [5][6] and

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

• enantioselectivity (up to 98% ee; entries 1–29, Table 23) [51]. Also, the addition reaction to the structurally similar N-Cbz-4-quinolone was tested, resulting in the corresponding products with only low to moderate yields (31–65%) and moderate to good enantioselectivities (40–89% ee; entries 30–38, Table 23) [51

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• ] photocycloaddition of quinolone 170. The proposed mechanism proceeds via hydrogen-bonded complex 171, which is sensitised by the pendant benzophenone to its triplet excited state 171*. The following cycloaddition completes the cycle and generates the desired cyclobutane product 173 in excellent conversion but poor

• Bach’s recent review on the subject [13]. Photocatalyst 174 was first used in a cyclisation reaction where the putative mechanism involves a hydrogen bonding complex 175 between the catalyst and quinolone substrate 176 (Scheme 26) [2]. Subsequent photoexcitation promotes a photoinduced electron transfer

• catalyst to an intermolecular photocycloaddition between quinolone 209 and maleimide 210 (Scheme 32b) [92]. After extensive mechanistic investigations, the proposed mechanism for this reaction is markedly different to the intramolecular example in Scheme 32a. Firstly, the hydrogen-bonded complex 211 that

4-Hydroxy-3-methyl-2(1H)-quinolone, originally discovered from a Brassicaceae plant, produced by a soil bacterium of the genus Burkholderia sp.: determination of a preferred tautomer and antioxidant activity

• Dandan Li,
• Naoya Oku,
• Yukiko Shinozaki,
• Yoichi Kurokawa and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2020, 16, 1489–1494, doi:10.3762/bjoc.16.124

• 939-8630, Japan Department of Bioscience and Biotechnology, Fukui Prefectural University, Eiheiji-cho, Fukui, Japan 10.3762/bjoc.16.124 Abstract 4-Hydroxy-3-methyl-2(1H)-quinolone (1), a molecule known for a long time and recently discovered from a Brassicaceae plant Isatis tinctoria without

• compounds and a synthetic preparation of 1, allowed its first full NMR characterization and identification of 2-quinolone but not 2-quinolinol (2) as the preferred tautomer for this heterocyclic system. While the metal-chelating activity was negligible, compound 1 at 10 μM, a concentration lower than that

• in the host organisms. Keywords: antioxidant; Burkholderia sp; quinolone; soil bacterium; Zn2+ enrichment culture; Findings 4-Hydroxy-2(1H)-quinolone (3) is a unique structural motif mostly found in alkaloids from rutaceous plants (family Rutaceae) [1][2]. This motif has several tautomeric forms

Copper-based fluorinated reagents for the synthesis of CF₂R-containing molecules (R ≠ F)

• Louise Ruyet and
• Tatiana Besset

Beilstein J. Org. Chem. 2020, 16, 1051–1065, doi:10.3762/bjoc.16.92

• , pyrimidine and quinolone derivatives, for instance, when the PhenCuCF2CF3 complex was used as the pentafluoroethyl source (24 examples, up to 99% 19F NMR yield and up to 93% isolated yield, Scheme 15). Note that a complete mechanistic study was recently reported to explain the reactivity of this well

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• , and Grignard reagents. Review Copper-catalysed C–C bond-forming reactions at the heterocycle The direct synthesis of chiral heterocyclic molecules from pyridine, quinolone, or indole derivatives is advantageous due to the abundance of such building blocks. Unfortunately, establishing catalytic

• ]. Initially, the methodology was developed for additions to N-Cbz-4-quinolone-based substrates, and the catalytic system was demonstrated to facilitate the addition of a wide variety of reagents, including linear, α-, β-, and γ-substituted, as well as aryl Grignard reagents. The subsequent broadening of the

• quinolone scope revealed that substrates bearing Me, Br, CF3, ether, amide, and ester substituents, respectively, were also tolerated successfully. In addition, the catalytic system was applied to the synthesis of the natural product (+)-angustureine with an excellent outcome (92% yield, 97% ee) (Scheme 6A

Cyclopropanation–ring expansion of 3-chloroindoles with α-halodiazoacetates: novel synthesis of 4-quinolone-3-carboxylic acid and norfloxacin

• Sara Peeters,
• Linn Neerbye Berntsen,
• Pål Rongved and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2019, 15, 2156–2160, doi:10.3762/bjoc.15.212

• efficient way of synthesizing two synthetically versatile 4-quinolone-3-carboxylate building blocks by cyclopropanation-ring expansion of 3-chloroindoles with α-halodiazoacetates as the key step. This novel transformation was applied towards the synthesis of the antibiotic drug norfloxacin. Keywords

• : catalysis; cyclopropanation; indole; norfloxacin quinoline; quinolone; Rh(II); ring expansion; Introduction The development and use of metal carbenes occupy a central part in the field of the C–H functionalization [1]. Among the metal carbenes, the transient Rh carbenes, usually made by Rh-catalyzed

• indoline cyclopropane intermediate and elimination of HX. The 4-quinolone-3-carboxylic acid scaffold (Figure 1) is regarded as a privileged scaffold in medicinal chemistry, due to the frequent appearance of this structural subunit in many commercial drugs [16][17][18][19][20][21], and a large variety of

Catalyst-free assembly of giant tris(heteroaryl)methanes: synthesis of novel pharmacophoric triads and model sterically crowded tris(heteroaryl/aryl)methyl cation salts

• Rodrigo Abonia,
• Luisa F. Gutiérrez,
• Braulio Insuasty,
• Jairo Quiroga,
• Kenneth K. Laali,
• Chunqing Zhao,
• Gabriela L. Borosky,
• Samantha M. Horwitz and
• Scott D. Bunge

Beilstein J. Org. Chem. 2019, 15, 642–654, doi:10.3762/bjoc.15.60

• State University, Kent, OH 44242, USA 10.3762/bjoc.15.60 Abstract A series of giant tris(heteroaryl)methanes are easily assembled by one-pot three-component synthesis by simple reflux in ethanol without catalyst or additives. Diversely substituted indoles (Ar1) react with quinoline aldehydes, quinolone

• ternary heteroarylmethane-inspired hybrids by coupling diversely substituted indoles (Ar1) with quinoline aldehydes, quinolone aldehydes, chromone aldehydes, and fluorene aldehydes (Ar2CHO) and coumarins (Ar3) in 1:1:1 ratio by simple reflux in ethanol solvent to form the corresponding highly crowded tris

• by hydride abstraction from (Ar1Ar1Ar2)CH are also demonstrated. Results and Discussion At the onset a series of non-commercial N-alkylindoles 1{4–10} and quinoline-/quinolone aldehydes 6{1-7} were prepared (Scheme 3 and Scheme 4). The N-methyl-, N-butyl- and N-benzylindoles 1{4–10} were synthesized

Study on the regioselectivity of the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide

• Pedro N. Batalha,
• Luana da S. M. Forezi,
• Maria Clara R. Freitas,
• Nathalia M. de C. Tolentino,
• Ednilsom Orestes,
• José Walkimar de M. Carneiro,
• Fernanda da C. S. Boechat and
• Maria Cecília B. V. de Souza

Beilstein J. Org. Chem. 2019, 15, 388–400, doi:10.3762/bjoc.15.35

• group, in a regiosselective way. In this work, we employed DFT methods to investigate the regiosselective ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide, evaluating its acid/base behavior and possible reaction paths. Keywords: alkylation; carboxamide; oxoquinoline; quinolone

Thiol-free chemoenzymatic synthesis of β-ketosulfides

• Adrián A. Heredia,
• Martín G. López-Vidal,
• Marcela Kurina-Sanz,
• Fabricio R. Bisogno and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2019, 15, 378–387, doi:10.3762/bjoc.15.34

• moieties occurring in bioactive molecules, such as the immunosuppresor oxisurane [49], quinolone vasodilator flosequinan [50], and potential drugs for the treatment of diabetes [51]. As such, employing simple transformations, compound 2a was conveniently oxidised in moderate to good isolated yields (45

Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS

• Sven Thierbach,
• Max Wienhold,
• Susanne Fetzner and
• Ulrich Hennecke

Beilstein J. Org. Chem. 2019, 15, 187–193, doi:10.3762/bjoc.15.18

• are associated with quorum sensing and virulence of the human pathogen Pseudomonas aeruginosa, have been prepared. While the synthesis by direct methylation was successful for 3-unsubstituted 2-heptyl-4(1H)-quinolones, methylated derivatives of the Pseudomonas quinolone signal (PQS) were synthesized

• unsaturation and can be O- or N-methylated [1][2][3]. In the opportunistic pathogen Pseudomonas aeruginosa, AQ derivatives with heptyl or nonyl side chains are prevalent [3][7][8][9]. 2-Heptyl-3-hydroxy-4(1H)-quinolone (Pseudomonas quinolone signal, PQS) and its biosynthetic precursor 2-heptyl-4(1H)-quinolone

• (HHQ, 1) are important signaling molecules involved in quorum sensing and as such play an important role in virulence regulation [3][10][11][12]. Another metabolite from the AQ biosynthesis pathway of P. aeruginosa is 2-heptyl-1-hydroxy-4(1H)-quinolone (generally referred to as 2-heptyl-4

Synthesis and biological evaluation of 1,2-disubstituted 4-quinolone analogues of Pseudonocardia sp. natural products

• Stephen M. Geddis,
• Teodora Coroama,
• Suzanne Forrest,
• James T. Hodgkinson,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2018, 14, 2680–2688, doi:10.3762/bjoc.14.245

• analogues was observed to inhibit production of the virulence factor pyocyanin in the human pathogen Pseudomonas aeruginosa, which may be a result of their similarity to the Pseudomonas quinolone signal (PQS) quorum sensing autoinducer. This provided new insights regarding the effect of N-substitution in

• PQS analogues, which has been hitherto underexplored. Keywords: antibiotics; cross-coupling; heterocycles; quorum-sensing; structure–activity relationships; Introduction The quinolone core has long been implemented in structures possessing formidable activity in a broad range of fields, including

• antibiotics, bacterial signalling and iron metabolism [1]. Structural optimisation of quinolones possessing intriguing properties can lead to the discovery of important drug classes, as demonstrated by the fluoroquinolone antibiotics, which were inspired by the observation of an antibacterial quinolone side

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• coordinate population-wide group behaviours in the infection process like concerted secretion of virulence factors. One very important signalling network is the Pseudomonas quinolone signal (PQS) QS. With the aim to devise novel and innovative anti-infectives, inhibitors have been designed to address the

• disruption of the Pseudomonas quinolone signal quorum sensing system (pqs QS). Review Antimicrobial resistance and clinical relevance of Pseudomonas aeruginosa P. aeruginosa is one of the threatening ESKAPE pathogens and has regularly been attributed with the label ‘superbug’ [11]. In 2017, the World Health

• been described that the amount of quinolone-based quorum sensing (pqs QS; vide infra) in those patients correlates with a negative prognosis and might function as a possible biomarker for the severity of the infection [21]. Quroum sensing (QS) In general, the term quorum sensing describes a population

Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections

• Matthew B. Calvert,
• Varsha R. Jumde and
• Alexander Titz

Beilstein J. Org. Chem. 2018, 14, 2607–2617, doi:10.3762/bjoc.14.239

• , multiple QS mechanisms exist within one species. For example in P. aeruginosa, four signaling systems have been identified to date, which are highly interconnected and mutually influence each other [30]. Some bacteria employ rather specific quorum sensing molecules, such as the Pseudomonas Quinolone Signal

Impact of Pseudomonas aeruginosa quorum sensing signaling molecules on adhesion and inflammatory markers in endothelial cells

• Carmen Curutiu,
• Florin Iordache,
• Veronica Lazar,
• Aurelia Magdalena Pisoschi,
• Aneta Pop,
• Mariana Carmen Chifiriuc and
• Alina Maria Hoban

Beilstein J. Org. Chem. 2018, 14, 2580–2588, doi:10.3762/bjoc.14.235

• cells were stimulated with 20 µM of main P. aeruginosa QSSMs (OdDHL = N-(3-oxododecanoyl)-L-homoserine lactone, C4HSL = N-butyryl-L-homoserine lactone, PQS = 2-heptyl-3-hydroxy-4(1H)-quinolone and HHQ = 2-heptyl-4-quinolone). Adherence to endothelial cells, inert substratum and biofilm formation was

• infections. P. aeruginosa produce two types of quorum-sensing signaling molecules (QSSMs): N-acylhomoserine lactones (AHL) and 2-alkyl-4-quinolone (PQS) derivatives. The AHLs molecules described so far in P. aeruginosa belong at two quorum sensing (QS) systems: las and rhl systems whose autoinducer (AI

• ) molecules are N-(3-oxododecanoyl)homoserine lactone (OdDHL, 3-oxo-C12-HSL), and N-butyryl-L-homoserine lactone (C4-HSL), respectively. AHL systems are interconnected by a third mechanism that uses signaling molecules such as 2-alkyl-4-quinolone (AQ), the most relevant one being 3-hydroxy-4-quinolone (PQS

Gold-catalyzed post-Ugi alkyne hydroarylation for the synthesis of 2-quinolones

• Xiaochen Du,
• Jianjun Huang,
• Anton A. Nechaev,
• Ruwei Yao,
• Jing Gong,
• Erik V. Van der Eycken,
• Olga P. Pereshivko and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2018, 14, 2572–2579, doi:10.3762/bjoc.14.234

• . Subjecting these adducts to a gold-catalyzed intramolecular alkyne hydroarylation process allowed to efficiently construct the 2-quinolone core bearing a branched substituent on the nitrogen atom. Keywords: gold catalysis; hydroarylation; 2-quinolones; Ugi reaction; Introduction Quinoline and its oxidized

• derivatives, 2-quinolone and 4-quinolone, are the core structural elements of many natural products and pharmaceutical agents [1][2][3]. In particular, 2-quinolone derivatives show a broad range of biological activities including antiviral [4][5][6][7], antimicrobial [8][9], antiparasitic [10][11], anti

• functionalization [25][26][27][28][29] of the 2-quinolone scaffold has become a budding research trend. In the last decade, a great number of efficient approaches has been developed utilizing transition metal-catalyzed [30][31][32], Lewis acid-mediated [33], and radical cyclizations [34] of various aniline

Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives

• Nicholas G. Jentsch,
• Jared D. Hume,
• Emily B. Crull,
• Samer M. Beauti,
• Amy H. Pham,
• Julie A. Pigza,
• Jacques J. Kessl and
• Matthew G. Donahue

Beilstein J. Org. Chem. 2018, 14, 2529–2536, doi:10.3762/bjoc.14.229

• the benzene ring of the quinolone [13]. The known synthesis of quinoline core 8 has been published in a one-pot, two-step reaction from 4-bromoaniline (7) and diethyl acetylsuccinate in 36% yield (Scheme 2) [14][15]. However, our attempts to repeat and scale-up this procedure beyond a few hundred

• intramolecular 6-exo-trig cyclization and subsequent proton transfer to the aminal oxygen D. Elimination of the 2-hydroxy group from D then affords the 4-quinolone E that tautomerizes via [1,5]-hydride shift to form quinoline 10. Given the success of employing ethyl acetoacetate in the quinoline