Synthesis of new tricyclic 5,6-dihydro-4H-benzo[b][1,2,4]triazolo[1,5-d][1,4]diazepine derivatives by [3⁺ + 2]-cycloaddition/rearrangement reactions

• Lin-bo Luan,
• Zi-jie Song,
• Zhi-ming Li and
• Quan-rui Wang

Beilstein J. Org. Chem. 2018, 14, 1826–1833, doi:10.3762/bjoc.14.155

• -dihydro-4(1H)-quinolone 6a [46]. However, it was odd that the oxidation using the hypervalent iodine(III) reagent PhI(OAc)2 as described for phenylhydrazones 7 failed to produce the expected α-acetoxy-ethoxycarbonyl compound 12. Instead, the hydrazone 11 remained intact and was recovered. Therefore, we

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

• inhibited the growth of the marine bacterium Tenacibaculum maritimum, an etiological agent of skin ulcers in marine fish, offering new opportunities to develop antibacterial drugs for fish farming. Keywords: antimicrobial; Burkholderia; quinolone; skin ulcer; Tenacibaculum maritimum; Findings Bacteria of

• correspond to two rings, which constitutes a fused bicyclic structure as suggested by the number of available aromatic carbons (eleven). A 4-quinolone substructure was indicated by a peak-splitting at the 340–320 nm region in the UV spectrum (328 and 322 nm) [13]. Indeed, 1H NMR resonances at the down field

• region was superimposable on those of known 2-heptyl-4(1H)-quinolone (2, Supporting Information File 1, Figure S11). The COSY and HMBC correlations also supported this assignment (Figure 2; Supporting Information File 1, Figures S8 and S10). An extension of a 2-nonenyl group (C9–C17) at C2 was supported

Rhodium-catalyzed C–H functionalization of heteroarenes using indoleBX hypervalent iodine reagents

• Erwann Grenet,
• Ashis Das,
• Paola Caramenti and
• Jérôme Waser

Beilstein J. Org. Chem. 2018, 14, 1208–1214, doi:10.3762/bjoc.14.102

• -pyridinone ring is present in milrinone (1), used to treat heart failure, while a 4-pyridinone is part of mimosine (2), an alkaloid isolated from Mimosa pudica. A benzene-fused pyridinone – a quinolone – can be found in brexpiprazole (3), a drug used against schizophrenia. In addition, the indole core is

• -oxide function, we were able to access 6-(indol-3-yl)pyridinone and 8-(indol-3-yl)quinolone. The developed transformations give access to important heterocyclic building blocks for synthetic and medicinal chemistry and set the stages for the development of other C–H heteroarylation processes based on

• compounds with pyridinone, quinolone and indole cores. C–H functionalization of pyridinones and quinoline N-oxides. Scope and limitations of the Rh-catalyzed C–H activation of [1,2'-bipyridin]-2-one. Scope of the Rh-catalyzed peri C–H activation of quinoline N-oxides. Product modifications. Optimization of

An overview of recent advances in duplex DNA recognition by small molecules

• Sayantan Bhaduri,
• Nihar Ranjan and
• Dev P. Arya

Beilstein J. Org. Chem. 2018, 14, 1051–1086, doi:10.3762/bjoc.14.93

Halogen-containing thiazole orange analogues – new fluorogenic DNA stains

• Aleksey A. Vasilev,
• Meglena I. Kandinska,
• Stanimir S. Stoyanov,
• Stanislava B. Yordanova,
• David Sucunza,
• Juan J. Vaquero,
• Obis D. Castaño,
• Stanislav Baluschev and
• Silvia E. Angelova

Beilstein J. Org. Chem. 2017, 13, 2902–2914, doi:10.3762/bjoc.13.283

• (Experimental part) with ethanol as the reaction medium. It is worth noting that replacement of the methanol with the environmentally more benign and less harmful ethanol significantly decreases the formation of blue-colored self-condensation byproducts (probably a chromophore constructed from quinolone and

• the quinolone moiety is consistent with the experimentally observed behavior (TO-7Cl compared to TO). There is no difference in the predicted maxima for TO-7Cl and 5a, so the experimentally observed 4 nm red shift upon replacement of the methyl by a benzyl group in the same moiety is not manifested in

• lower absorption wavelength of TO. In compounds 5a–d the HOMO was found to be populated over the entire molecular system except for the benzyl fragment and the substituents in position 7 in the quinolone moiety. The LUMO was found to be delocalized over the quinolinium and, to a lesser extent, the

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• -tetramethylpiperidine 1-oxyl), the detection of Ag(0) by X-ray photoelectron spectroscopy, the retardation of the reaction in absence of air and an 18O-labeling reaction led the authors to propose the mechanism described in Scheme 4 [23]. Because some limitations appeared with heterocycles such as quinolone, indole

Solvent-free copper-catalyzed click chemistry for the synthesis of N-heterocyclic hybrids based on quinoline and 1,2,3-triazole

• Martina Tireli,
• Silvija Maračić,
• Stipe Lukin,
• Marina Juribašić Kulcsár,
• Dijana Žilić,
• Mario Cetina,
• Ivan Halasz,
• Silvana Raić-Malić and
• Krunoslav Užarević

Beilstein J. Org. Chem. 2017, 13, 2352–2363, doi:10.3762/bjoc.13.232

• derivatives and it was largely helpful for calculating the Raman spectra for monitoring purposes. It corroborated the substitution of the phenyl-1-(1,2,3-triazolyl)methyl unit at O-4 position of the quinolone heterocycle and formation of the 1,2,3-triazole ring in compounds 5–8 (Figure 5 and Supporting

Continuous-flow processes for the catalytic partial hydrogenation reaction of alkynes

• Carmen Moreno-Marrodan,
• Francesca Liguori and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2017, 13, 734–754, doi:10.3762/bjoc.13.73

• more usual strategy is the so-called “selective poisoning”, i.e., the improvement of the catalyst’s selectivity by the addition of variable, often large, amount of contaminants, either organic ligands (quinolone [65][66], phosphine [67]), carbon monoxide [68], sulfides [69], sulfoxides [70][71] defined

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• after 24 h. Remarkably, when the catalyst loading was reduced to 1 mol %, the product could still be obtained in 69% yield after 96 h. Although the hidden acid catalysis due to the trace amounts of HI was not ruled out, the proposed N-halogen bond formation between quinolone and perfluoroiododecane

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

• coordinate the production of its broad spectrum of virulence factors to facilitate colonization and infection of its host. Hereby, the enzyme PqsD is a virulence related quorum sensing signal synthase that catalyzes the central step in the biosynthesis of the Pseudomonas quinolone signals HHQ and PQS. We

• . 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

Amidofluorene-appended lower rim 1,3-diconjugate of calix[4]arene: synthesis, characterization and highly selective sensor for Cu²⁺

• Rahman Hosseinzadeh,
• Mohammad Nemati,
• Reza Zadmard and
• Maryam Mohadjerani

Beilstein J. Org. Chem. 2016, 12, 1749–1757, doi:10.3762/bjoc.12.163

• ]arene bearing anthraceneisoxazolymethyl [3], quinolone [28], 5-nitrosalicylaldehyde [29], 3-alkoxy-2-naphthoic acid [30], coumarine [31] and benzothiazole [10][15] groups. In continuation of our studies on developing novel chemosensors containing fluorenyl moieties as fluorogenic group [32][33][34], we

Discovery of an inhibitor of the production of the Pseudomonas aeruginosa virulence factor pyocyanin in wild-type cells

• Bernardas Morkunas,
• Balint Gal,
• Warren R. J. D. Galloway,
• James T. Hodgkinson,
• Brett M. Ibbeson,
• Yaw Sing Tan,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2016, 12, 1428–1433, doi:10.3762/bjoc.12.137

• -oxododecanoyl)-L-homoserine lactone (OdDHL) and it’s cognate receptor LasR (Figure 1) [20][21][22]. Interlinking these two AHL signalling systems is a third signaling system utilising a quinolone signalling molecule (termed Pseudomonas quinolone signal, PQS) [20] to form an intricate hierarchical signaling

• knowledge, compounds of this structural sub-class have never been screened for the ability to modulate pyocyanin production (or any other quorum sensing-regulated phenotypes). Thus, quinolone 4 was evaluated for its ability to inhibit pyocyanin production by the wild-type P. aeruginosa strain PAO1 (Figure

• mode of action of 4 and structure–activity relationship studies are ongoing and results will be reported in due course. BHL and OdDHL are two natural AHL-based signaling molecules used by P. aeruginosain quorum sensing. PQS is a natural quinolone signaling molecule also used by P. aeruginosa in quorum

Reactions of N,3-diarylpropiolamides with arenes under superelectrophilic activation: synthesis of 4,4-diaryl-3,4-dihydroquinolin-2(1H)-ones and their derivatives

• Larisa Yu. Gurskaya,
• Diana S. Belyanskaya,
• Dmitry S. Ryabukhin,
• Denis I. Nilov,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2016, 12, 950–956, doi:10.3762/bjoc.12.93

• of compounds 5 and 6 with arenes in TfOH were checked. Analogously to other heteroaromatic aldehydes of the series of pyridine [19], quinolone [20], pyrazol [21], and imidazole [22], the superelectrophilic activation of the formyl group in 5 was expected. Indeed, compounds 5a,b and d reacted with

Iridium/N-heterocyclic carbene-catalyzed C–H borylation of arenes by diisopropylaminoborane

• Mamoru Tobisu,
• Takuya Igarashi and
• Naoto Chatani

Beilstein J. Org. Chem. 2016, 12, 654–661, doi:10.3762/bjoc.12.65

• a 1.1:1 mixture of 2-borylated and 2,5-diborylated products under our standard conditions (Table 2, entry 10). 2-Substituted thiophenes 14 and 15 and furan 16 were borylated successfully at the 5-positions (Table 2, entries 11–13). Electron-deficient heteroarenes such as pyridine and quinolone

Synthesis of quinoline-3-carboxylates by a Rh(II)-catalyzed cyclopropanation-ring expansion reaction of indoles with halodiazoacetates

• Magnus Mortén,
• Martin Hennum and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2015, 11, 1944–1949, doi:10.3762/bjoc.11.210

• commercially available indoles in combination with the scope of the reaction makes the cyclopropanation-ring expansion an attractive method for an efficient synthesis of quinolone-3-carboxylates. Experimental Detailed experimental procedures and analytical data for the compounds are available in Supporting

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• , dihydroacridine, and quinolone cores are features regularly found in these alkaloid skeletons. The lack of hydrogen atoms next to quaternary carbon atoms for two or three rings makes the chemical shift assignment a difficult task. In this regard, one of the aims of this review is the compilation of previously

• comprised of four to eight fused rings including heterocycles [34][35][36][37][38][39]. Acridine, acridone, dihydroacridine, and quinolone cores [33][40] are features regularly found in these alkaloid skeletons. The high conjugation of their structure induces a strong electron delocalization, leading to

• was subsequently transformed into a quinolone benzyl ether under reflux conditions. A quinoline triflate ester was prepared from the quinolone and coupled to trimethyl(2-nitrophenyl)stannane by Stille coupling catalyzed by palladium acetate. The afforded nitrophenylquinoline was hydrolyzed and

Consequences of the electronic tuning of latent ruthenium-based olefin metathesis catalysts on their reactivity

• Karolina Żukowska,
• Eva Pump,
• Aleksandra E. Pazio,
• Krzysztof Woźniak,
• Luigi Cavallo and
• Christian Slugovc

Beilstein J. Org. Chem. 2015, 11, 1458–1468, doi:10.3762/bjoc.11.158

• complexes possess some practical properties, namely they tend to be thermally stable, enabling applications at elevated temperatures. Being aware of the various advantages of such systems, we set out to study substituted quinolone–ruthenium chelates in view of their trans–cis susceptibility and its

Synthesis and spectroscopic properties of β-triazoloporphyrin–xanthone dyads

• Dileep Kumar Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2015, 11, 1434–1440, doi:10.3762/bjoc.11.155

• porphyrins with diverse functionalities such as quinolone [19], ferrocene [20], carbohydrate [21] and fullerene [22] through a copper(I)-catalyzed Huisgen–Sharpless–Meldal 1,3-dipolar cycloaddition reaction [23][24]. Some of these triazolo-bridged porphyrin dyads have shown an efficient intramolecular energy

A new and efficient procedure for the synthesis of hexahydropyrimidine-fused 1,4-naphthoquinones

• Marcelo Isidoro P. Reis,
• Vinícius R. Campos,
• Jackson A. L. C. Resende,
• Fernando C. Silva and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2015, 11, 1235–1240, doi:10.3762/bjoc.11.137

• naphthoquinones (Figure 1) such as naphtho[2,3-b]furan [5][6][7][8][9][10][11][12][13][14], naphtho-pyran [15][16][17][18], benzo[f]indole [19][20][21][22][23][24], benzo[g]quinolone [25], benzo[b]carbazole [26], naphtho[2,3-b]thiophene [27][28][29][30][31][32][33] and naphtho[2,3-b]]oxazole [34] have been

Natural phenolic metabolites with anti-angiogenic properties – a review from the chemical point of view

• Qiu Sun,
• Jörg Heilmann and
• Burkhard König

Beilstein J. Org. Chem. 2015, 11, 249–264, doi:10.3762/bjoc.11.28

• , acylphloroglucinols, quinolone-substituted phenols and 4-amino-2-sulfanylphenol derivatives are discussed. Some important aspects of the described pharmacological activities of the compounds are summarized in Table 3. Review 4-Hydroxybenzyl alcohol 4-Hydroxybenzyl alcohol (HBA, 1) (Figure 1) is a well-known phenolic

• acts to suppress the signaling pathways mediated by VEGFR2, inducing apoptosis in endothelial cells. Quinoline-substituted phenols To date, quinolone-substituted phenols (Qsps) have not been reported as natural secondary metabolites, although quinolone and alkylated phenols are common structural

• , −40 °C; −40 °C → rt, 3 h; (2) Na2S2O4, rt, 30 min; (c) MeOH/H2O 1:1, reflux. Synthesis of quinolone-substituted phenol 20. Reagents and conditions: (a) Ac2O, 2-hydroxybenzaldehyde, 130 °C; (b) (1) Br2, AcOH, (2) Ac2O; (c) (1) DBU, THF, (2) Ac2O; (d) Na2CO3, MeOH/THF. Synthesis of quinolone-substituted

Syntheses of fluorooxindole and 2-fluoro-2-arylacetic acid derivatives from diethyl 2-fluoromalonate ester

• Antal Harsanyi,
• Graham Sandford,
• Dmitri S. Yufit and
• Judith A.K. Howard

Beilstein J. Org. Chem. 2014, 10, 1213–1219, doi:10.3762/bjoc.10.119

• structurally sophisticated selectively fluorinated systems. For example, 2-fluoromalonate esters have been used for the preparation of various α-fluorocarboxylic acids [28][29][30][31][32], heterocycles, such as fluoropyrimidine [33] and quinolone [34] derivatives, alkylated [35] and Michael addition [36][37

Aza-Diels–Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome

• Amitabh Jha,
• Ting-Yi Chou,
• Zainab ALJaroudi,
• Bobby D. Ellis and
• T. Stanley Cameron

Beilstein J. Org. Chem. 2014, 10, 848–857, doi:10.3762/bjoc.10.81

• -a]isoquinolinone which has been isolated from Berberis darwinii [1][2][3]. Cryptolepine is an indolo[3,2-b]quinolone alkaloid found in west African shrub Cryptolepis sanguinolenta, a plant used in traditional medicine for the treatment of malaria [3]. This alkaloid has shown potent antiplasmodial [4

• isoindolo[2,1-a]quinolone derivatives involves N-acyliminium ions or appropriate electron-deficient Schiff bases and subsequent [4 + 2] inverse-demand hetero-Diels–Alder cycloadditions with alkenes [11][12][13][14][15][16][17]. Vinylic systems from isoeugenol [11], cyclopentadiene [12], enones [13], vinyl

• the N-aryl group undergo intramolecular electrophilic addition to the alkene yielding isoindolo[2,1-a]quinolines under acidic conditions [18]. Isoindolo[2,1-a]quinolone cores have also been prepared via an aldol-type intramolecular cyclization reaction of N-(2-acetylaryl)phthalimide under anhydrous

New syntheses of 5,6- and 7,8-diaminoquinolines

• Maroš Bella and
• Viktor Milata

Beilstein J. Org. Chem. 2013, 9, 2669–2674, doi:10.3762/bjoc.9.302

• -benzoselenadiazole skeleton while the pyridine ring can be obtained by transformation of the pyridone core [15]. The synthesis of 7,8-diaminoquinoline (3) starting from selenadiazolo[3,4-h]quinolone 1 is depicted in Scheme 1. In the first step, the aromatization of the pyridone ring by chlorination with POCl3 in DMF

• , which worked reliably on related azoloquinolones [15], was attempted. However, in the case of selenadiazolo[3,4-h]quinolone 1, only decomposition products were observed. On the other hand, chlorination with neat POCl3 at 90 °C afforded 6-chloroselenadiazoloquinoline 2 in 74% yield after

• hydrochloride 5 with diimine 7 [18][19] proceeded smoothly at room temperature affording pyridoquinoxaline 8 in high yield (Scheme 2). The same reaction sequence (chlorination and reductive deselenation) was applied to selenadiazolo[3,4-f]quinolone 9 (Scheme 3). The treatment of selenadiazoloquinolone 9 with

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• ] and neatly introduces the required chloride substituent at the 5-position. While isolated pyridines are a vital component in numerous drugs the related quinoline/quinolone scaffolds are becoming increasingly common. One such example is nalidixic acid (1.101, in fact a naphthyridone, Figure 2

• ). Nalidixic acid is a prototype quinolone antibiotic that has been used extensively as an effective treatment against both gram positive and gram negative bacteria. In general, quinolone antibiotics act by interfering with the enzymes DNA-gyrase and/or topoisomerase of bacteria [55]. Moxifloxacin (1.102

• from the bacterial cell. Due to the elaborate substitution pattern of the parent quinolone ring systems these compounds are usually prepared via a linear consecutive sequence. In the case of moxifloxacin, an intramolecular base catalysed nucleophilic aromatic substitution is used to prepare the

Synthesis and biological activities of the respiratory chain inhibitor aurachin D and new ring versus chain analogues

• Xu-Wen Li,
• Jennifer Herrmann,
• Yi Zang,
• Philippe Grellier,
• Soizic Prado,
• Rolf Müller and
• Bastien Nay

Beilstein J. Org. Chem. 2013, 9, 1551–1558, doi:10.3762/bjoc.9.176

• Products, Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research (HZI) and Pharmaceutical Biotechnology, Saarland University, Campus C2 3, 66123 Saarbrücken, Germany 10.3762/bjoc.9.176 Abstract Aurachins are myxobacterial 3-farnesyl-4(1H)-quinolone derived

• class of compounds is characterized by a quinolone or quinoline nucleus substituted in position 3 or 4 by a farnesyl chain. In addition, aurachins can further be functionalized by biosynthetic oxidative processes [2][3][4][5]. Since then, additional members of this natural product family were discovered

• at an IC50 around 20 ng/mL (i.e., aurachins B, C and E, whereas aurachin D was 100- to 200-fold less active) [6]. This antimalarial activity was comparable to that of endochin (5) [13][14] and 2-methyl-4(1H)-quinolone analogues as determined in the course of important structure–activity optimization