Rhodopyran, a carboxylated hexahydrocyclopenta[b]pyran from Rhodococcus

• Enjuro Harunari,
• Sara Fushimi and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2026, 22, 1107–1113, doi:10.3762/bjoc.22.89

• metabolites include rhodostreptomycins [7], a quinoline antibiotic [8], rhodopeptins [9], lariatins [10], rhodochelin [11], and the pluramycin-class metabolite rausuquinone [12]. These examples illustrate the chemical diversity within the genus Rhodococcus, but its metabolite space remains far less explored

Palladium-catalyzed benzocyclization reactions of quinoline-2-carboxamides via sequential C–H/N–H functionalization

• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2026, 22, 905–914, doi:10.3762/bjoc.22.71

• University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan 10.3762/bjoc.22.71 Abstract A novel benzocyclization protocol has been developed for the synthesis of quinoline-fused lactams by palladium-catalyzed sequential C–H/N–H functionalization of quinoline-2-carboxamides and 1,2-dihaloarenes. The reaction

• proceeds at the C–H bond on the quinoline adjacent to the amide group and at the amide N–H bond in the presence of 10 mol % Pd(OAc)2 in o-xylene as a solvent to afford the cyclized product in 34% yield. The yield increases to 81% when the reaction is carried out with 80 mol % P(4-MeOC6H4)3 as a ligand and

• ; sequential reaction; Introduction Cyclic structures comprising nitrogen-containing multifused rings are extremely important because such heterocycle-fused cyclic structures [1][2] are found in various advanced materials [3][4] and biologically essential molecules [5][6][7]. Quinoline is a particularly

Harnessing light energy with molecules

• Grace G. D. Han,
• Mogens Brøndsted Nielsen and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2026, 22, 680–682, doi:10.3762/bjoc.22.52

• study of substituent effects in a large selection of N-acetylated phenylazopyrazole photoswitches. Pittelkow, Antonov, and co-workers [17] present a study on tautomerism and switching in 7-hydroxy-8-(azophenyl)quinoline and similar π-expanded azobenzene compounds. The photoisomerization quantum yield is

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

Recent advances in the stereoselective synthesis of distal biaxially chiral molecules

• Fanxing Zhou,
• Chen Zhang,
• Lingyu Sun,
• Yiyun Fang,
• Siming Zheng,
• Lina Hu,
• Mengyang Shen,
• Zhen Zhao,
• Wei Xu,
• Yunqiang Sun and
• Zi-Qiang Rong

Beilstein J. Org. Chem. 2026, 22, 461–479, doi:10.3762/bjoc.22.34

• ligands (Scheme 3) [44]. The resulting catalysts 18 demonstrated remarkable efficiency in the asymmetric transfer hydrogenation of quinoline derivatives. Along similar lines, Zhang and co-workers introduced an additional axial chirality element into a ligand framework, affording a pair of diastereomeric

• assembly of complex distal biaxial architectures that are difficult to access via direct or stepwise axis formation alone. In 2019, Bertuzzi and co-workers achieved the first enantioselective synthesis of an axially chiral indole–quinoline system (Scheme 25) [64]. They employed a central-to-axial oxidative

• chiral polysubstituted naphthalene scaffolds. Enantioselective Ni-catalyzed Suzuki–Miyaura cross-coupling reaction. The stereoselective synthesis of axial chiral indole–quinoline systems. The synthesis of bisbenzofuran atropisomeric oligoarenes containing two distal C–C stereogenic axes. Funding This

A mild and atom-efficient four-component cascade strategy for the construction of biologically relevant 4-hydroxyquinolin-2(1H)-one derivatives

• 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 and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2026, 22, 244–256, doi:10.3762/bjoc.22.18

• -hydroxyquinoline core – 3-(6-halo-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)-3-(3,4-dimethoxyphenyl)propanoates (Figure 2). The C6 position of the quinoline ring was halogenated with fluorine, chlorine, or bromine, as halogenation at this site is known to influence both the physicochemical properties and biological

• -hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)-3-phenylpropanoic acid have not, to the best of our knowledge, been previously described. Structurally related compounds, such as 4-aryl-4,6-dihydro-2H-pyrano[3,2-c]quinoline-2,5(3H)-diones, have been reported only in a few cases, typically via multicomponent

• in the reaction mixture [44][45]. Previous studies have reported the synthesis of compounds structurally related to our targets – 4-aryl-4,6-dihydro-2H-pyrano[3,2-c]quinoline-2,5(3H)-diones – via multicomponent reactions catalyzed by various agents (Scheme 1) [37][38][39]. These one-pot reactions

Streptoquinolines A and B, new antibacterial meroterpenoids produced by Streptomyces sp. TMPU-A0679

• Akiho Yagi,
• Hitomi Tomura,
• Ami Konno and
• Ryuji Uchida

Beilstein J. Org. Chem. 2026, 22, 185–191, doi:10.3762/bjoc.22.12

• sesquiterpene fused with a highly substituted quinoline moiety. Further structural comparisons and specific rotation data revealed that 1 and 2 were epimers at C-4'. Compounds 1 and 2 both exhibited selective antibacterial activity against Gram-positive bacteria, including VRE and methicillin-resistant

• Staphylococcus aureus, with minimum inhibitory concentrations ranging from 6.25 to 12.5 µg/mL. These results expand the structural and biological diversities of drimane–quinoline-type meroterpenoids and highlight their potential as lead compounds for the development of new antibacterial agents targeting drug

• -resistant Gram-positive pathogens. Keywords: meroterpenoid; quinoline; Streptomyces sp; streptoquinoline; VRE; Introduction The emergence of antimicrobial-resistant bacteria has become a serious public health issue worldwide. Infections caused by these pathogens severely limit available treatment options

Total synthesis of natural products based on hydrogenation of aromatic rings

• Haoxiang Wu and
• Xiangbing Qi

Beilstein J. Org. Chem. 2026, 22, 88–122, doi:10.3762/bjoc.22.4

• saturation the aromatic ring facilitates synthetic chemists to efficiently synthesize natural products with complex three-dimensional structures. Recent advances in catalyst and ligand design have enabled unprecedented progress in the catalytic hydrogenation of (hetero)aromatic systems. Quinoline

• heterocycle part: Quinoline, one of the most accessible heteroaromatic feedstocks from natural and commercial sources, has long attracted interest in both synthetic and medicinal chemistry. A central challenge, however, is the selective catalytic hydrogenation of quinolines to the synthetically valuable

• hydrogenation of the polycyclic aromatic compound PyBQ to PyBTHQ using this catalyst in HFIP (Scheme 5) [50]. Under the optimized conditions, only the heteroaromatic part of quinoline was reduced selectively, while the benzene ring and pyridine remained unchanged. In 2020, Beller and co-workers used a manganese

Pentacyclic aromatic heterocycles from Pd-catalyzed annulation of 1,5-diaryl-1,2,3-triazoles

• Kaylen D. Lathrum,
• Emily M. Hanneken,
• Katelyn R. Grzelak and
• James T. Fletcher

Beilstein J. Org. Chem. 2025, 21, 2524–2534, doi:10.3762/bjoc.21.194

• ][21], and materials [22][23][24]. Numerous examples of 1,4-diaryl-1,2,3-triazoles with quinoline and isoquinoline subunits have been reported, including those with anticancer [25][26][27][28][29], antiviral [30][31], antibacterial [32], antifungal [33], antimalarial [34][35], antitubercular [36], and

• other bioactive properties [37][38][39][40][41][42][43][44]. In contrast, examples of 1,5-diaryl-1,2,3-triazoles with quinoline or isoquinoline subunits are lacking [45]. The neighboring proximity of the arene subunits in such 1,5-regioisomers allows for potential intramolecular annulation to form

• -diaryl-1,2,3-triazoles 7–12 into target pentacyclic aromatic heterocycles 13–18. Yields of annulation reactions for naphthalene-containing analog 13 (90%) was appreciably higher than for quinoline and isoquinoline derivatives 14–18 (31–72%). Due to triazole subunit connectivity to the napththalene

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• synthetic value of this method. In 2017, the Liu group established a precise control over cyclization sequences of 1,2-diphenylacetylenes by modulating the nitrogen-substitution patterns, enabling divergent syntheses of benzo[a]carbazole and indeno[1,2-c]quinoline derivatives (Scheme 9) [16]. When the

• intermediate 40 when using substrates with unsubstituted nitrogen. Concurrent oxygen-involved cyclization then furnished indeno[1,2-c]quinoline 41 (Scheme 9, path b). This work established a pathway-controlled strategy for efficient access to benzo[a]carbazole and indeno[1,2-c]quinoline derivatives. In 2019

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• and sustainability [95][96][97][98][99][100]. Numerous electrochemical constructions of cyclic compounds from alkynes have been developed. For examples, 2-aryl-3-sulfonyl-functionalized quinoline was formed by an electrochemical annulation of benzoxazinanone and p-arylsulfonyl hydrazide [101]. The

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• reaction with polycyclic arylamines 9 and various aromatic aldehydes 11, resulting in a range of quinoline-containing azahelicenes 12 with moderate yield and excellent enantioselectivity after DDQ-mediated oxidative aromatization (Scheme 3). Notably, they not only expanded the substrate scope to encompass

• enamide 6a and various aldehydes 7 to break the symmetry of substrates 52, which was followed by a one-pot oxidative aromatization mediated by DDQ to yield the quinoline-containing inherently chiral calix[4]arenes 53 (Scheme 15). Notably, the prochiral calix[4]arenes bearing a disubstitution pattern on

• the 1,3-phenyl rings (see 53d) or 1,3-diamino substitution (see 53e) on the calix[4]arene scaffold were also amenable to this method, which yielded a series of structurally diverse novel quinoline-containing inherently chiral calix[4]arenes. Moreover, by using CPA 4 as the optimal catalyst, the

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• -disubstituted and 4-substituted quinoline molecules. The developed strategy involves an earth-abundant Fe-catalyzed C(sp2)–C(sp2) bond cleavage of styrene, followed by the hydroamination of the cleaved synthons with arylamines and subsequent C–H annulation to yield two valuable quinoline derivatives. Key

• activation; C–H annulation; iron metal catalysis; quinolines; styrene; Introduction Quinolines are one of the essential heteroaromatic motifs that play a crucial role across diverse scientific fields due to their wide range of applications. In contemporary medicine, quinoline derivatives frequently appear

• in active pharmaceutical ingredients, therapeutic agents, and agrochemical formulations [1][2][3][4][5][6][7][8][9]. Around 60% of recently FDA-approved drugs contain heterocyclic compounds, with quinoline recognized as a key structural motif due to its significant anticancer, antifungal

Unique halogen–π association detected in single crystals of C–N atropisomeric N-(2-halophenyl)quinolin-2-one derivatives and the thione analogue

• Mai Uchibori,
• Nanami Murate,
• Kanako Shima,
• Tatsunori Sakagami,
• Ko Kanehisa,
• Gary James Richards,
• Akiko Hori and
• Osamu Kitagawa

Beilstein J. Org. Chem. 2025, 21, 1748–1756, doi:10.3762/bjoc.21.138

• )quinoline-2-thione, heterochiral layered polymers, in which (P)- and (M)-atropisomers were alternately connected, were formed through an n–π* interaction between a lone electron pair on the bromine atom and a π* orbital of the quinoline-2-thione. Keywords: atropisomers; C–N bond; halogen bond; quinolinones

• other C–N atropisomeric compounds. In this article, we report the synthesis of atropisomeric N-(2-halophenyl)quinolin-2-ones (1a: X = Br, 1b: X = Cl) and N-(2-bromophenyl)quinoline-2-thione (2a), and the analysis of halogen–mediated intermolecular interactions (halogen bonding and n–π* interaction

• ) observed in their single crystals. Results and Discussion Synthesis of quinoline-2-ones (thione), their enantiomer separation and rotational stability We focused on N-(2-halophenyl)quinolin-2-ones 1 and the thione analogue 2 as alternative substrates to verify chirality- and functional group-dependent

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• the emission into the visible region. The aza analogue demonstrated promising performance in OLEDs, confirming its potential for optoelectronic applications. Concurrently, Shirinian’s group synthesized a series of nitrogen-functionalized quinoline (NFQ)-based aza-oxa[5]helicenes 77a–f exhibiting

Tautomerism and switching in 7-hydroxy-8-(azophenyl)quinoline and similar compounds

• Lidia Zaharieva,
• Vera Deneva,
• Fadhil S. Kamounah,
• Nikolay Vassilev,
• Ivan Angelov,
• Michael Pittelkow and
• Liudmil Antonov

Beilstein J. Org. Chem. 2025, 21, 1404–1421, doi:10.3762/bjoc.21.105

• for clean switching. Obviously, a cooperative effect between substitution in the Ph ring and the 7-OH quinoline part is needed. In Scheme 3 and Table 3 the most suitable examples for cooperative substitution are shown. It seems that the substitution with strong donor substituents in the phenyl ring

• and on position 4 in 7-OH quinoline leads to results that are near to the desired (compounds 4–6). Very interesting is the result with strong electron-acceptor-substituted phenyl ring and donor substitution in 7OHQ part (compounds 7 and 8). Actually 7 and 8 fulfill most of the requirements for clean

• substitution in 7-OH quinoline, where the most of the requirements for clean switching are achieved if the K tautomer is considered as off-state and the E one as on-state. Experimental Synthesis and structure elucidation Materials The starting reagents and solvents were purchased from Sigma-Aldrich and

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• by Jutz and Kirchlechner in 1966 (Scheme 3) [36]. Condensation between phenalene 15 and pentafulvene 16 gave pentafulvene 17. Pentafulvene 17 was finally subjected to Ziegler–Hafner reaction in quinoline at 180 °C, resulting in the π-extended azulene 18 in 60% yield. A similar synthetic strategy was

• employed by Hara and co-workers in 1975 (Scheme 3) [37]. Compound 19 reacted with cyanine 20 to give pentafulvene 21. Compound 21 was later cyclized in quinoline at 180 °C giving non-alternant isomer of benzo[a]pyrene 22 in 62% isolated yield. PAH 22 has remarkable re-shifted optical absorption with λmax

• ]. Interestingly, initial attempts to convert 65 into 66 using various procedures for the palladium-catalysed C–H activation were unsuccessful, even when conducted at elevated temperatures. However, treatment of 65 with KOH in refluxing quinoline successfully yielded the desired PAH 66, albeit in a modest 15

Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-a]pyrazine scaffold

• Henry S. T. Smith,
• Ben Giuliani,
• Kanchana Wijesekera,
• Kah Yean Lum,
• Sandra Duffy,
• Aaron Lock,
• Jonathan M. White,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2025, 21, 1126–1134, doi:10.3762/bjoc.21.90

• Plasmodium parasites and recommends artemisinin combination therapy (ACT) for the treatment of both uncomplicated and severe malaria as a frontline treatment [1]. ACT includes the use of an artemisinin agent in concert with a partner drug (most often a quinoline drug), which possesses a different mechanism

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• exhibited higher stability compared to 4d and 5d transition metals. Through the study of a series of previous experiments, it was shown that the electron density of the nitrogen atom in the quinoline structure significantly affects the efficiency of nickel-electrocatalysis; however, other N,N- or N,O

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• this context, quinoline and its derivatives are privileged structures in several natural products and biologically active compounds, rendering this scaffold an important synthetic target. An attractive strategy to afford tetrahydroquinolines and quinolines is the Povarov reaction, a type of aza-Diels

• remarkable example, when formaldehyde was used, the reaction did not provide the desired quinoline 6 as the main product but rather julolidines 7 (Scheme 7) [31]. However, the use of paraformaldehyde and glycine can produce the desired products with low yields, but very expensive catalysts and complex

• compound and MMS, undergoes an aza-Diels–Alder cyclization with the alkyne, and after oxidation and aromatization steps generates quinoline II. Unfortunately, under these gentle and greener conditions, aliphatic alkynes remain unreacted, compared to the metal-catalyzed version developed by Xu et al. [37

Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• reaction of 2 with formamide was performed within only 3 h (Scheme 3), yielding the N-substituted thienopyrimidones 5a–e in 30–99% total yield (2 steps), as well with aliphatic and (hetero)aromatic substituents. Quinoline derivatives are prevalent in nature, and many exhibit a range of biological

• obtained 15 diversely substituted heteroannulated pyrimidones, employing privileged thiophene, quinoline and indole scaffolds in a rapid fashion, without the need of column chromatography, in a parallel setup. Heteroannulated pyrimidones in drug discovery: blockbuster drugs that are based on the privileged

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• motifs such as a benzofuran, indazole, and quinoline were also shown to undergo the desired Markovnikov amidation with high efficiency (23j–l). Several mechanistic experiments were performed to rationalize the reaction pathways. As shown in Figure 7, copper hydride, generated from a copper precatalyst

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• , Huang, and Mei et al. explored Cu-catalyzed electrochemical C(sp2)–H bromination of 8-aminoquinoline amide at the C5 site of quinoline using NH4Br as a brominating reagent under anoxic oxidation conditions (Figure 13) [64]. This catalytic reaction has a broad substrate scope, and further investigation

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• the coupling with copper triflate as catalyst, without ligand, co-catalyst or other additives. The reaction involved the formation of the imine XVII followed by alkynylation to propargylamine XVIII, cyclization, and oxidation to quinoline 23 (Scheme 17) [34]. Three component oxidative annulation to