Chemoenzymatic synthesis of the cardenolide rhodexin A and its aglycone sarmentogenin

• Fuzhen Song,
• Mengmeng Zheng,
• Dongkai Wang,
• Xudong Qu and
• Qianghui Zhou

Beilstein J. Org. Chem. 2025, 21, 2637–2644, doi:10.3762/bjoc.21.204

• , affording 4 in 64% yield (Table 1, entry 2). However, at a higher concentration (0.5 g/L), a significant amount of starting compound 5 remained unconverted even after 4 days, and only 30% of 4 was isolated (Table 1, entry 3). To our delight, upon adding 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) [29] as the

• (Table 1, entry 5). Delightfully, after adding 1% Tween 80 to the above fermentation broth, a complete conversion was observed in 4 days, and compound 4 was obtained in 64% yield (Table 1, entry 6). However, further increasing the substrate concentration to 2.0 g/L resulted in a much lower conversion

Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• scans) and 151 MHz for 13C NMR (20,480 scans), using an overnight experiment in DMSO-d6 at a concentration of 0.1 M. Specifically, the spectra showed either an absence of expected signals or a lack of signal multiplicity, which was apparent in both the 1H NMR and, more prominently, in the 13C NMR

Efficient solid-phase synthesis and structural characterization of segetalins A–H, J and K

• Liangyu Liu,
• Wanqiu Lu,
• Quanping Guo and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2025, 21, 2612–2617, doi:10.3762/bjoc.21.202

• , successful macrocyclization was achieved by employing benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate (PyBOP) as the coupling reagent in DMF at a concentration of 10−3 M. After cleavage from the resin and global side-chain deprotection, the crude cyclic peptides were purified by preparative

Silica gel with covalently attached bambusuril macrocycle for dicyanoaurate sorption from water

• Michaela Šusterová and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2025, 21, 2604–2611, doi:10.3762/bjoc.21.201

• concentration in solution reached equilibrium after 15 minutes, consistent with the equilibration time previously established for the non-covalent system SG-BnBU (Supporting Information File 1, Figure S5). Therefore, all subsequent sorption experiments were performed with an equilibration time of 15 minutes

• carried out in nitrogen atmosphere. The dicyanoaurate concentration in solution was determined according to UV–vis spectra recorded with a CARY 60 spectrophotometer (Agilent Technologies). NMR spectra were recorded on a Bruker Avance III 300 spectrometer (300.15 Hz, 298.15 K). Preparation of SG-NHCO-BU1

• min at 250 rpm. Afterwards, SG-NHCO-BU1 or SG-BU1 was left to settle and the supernatant was analyzed. The actual concentration of the anion left in the solution was calculated from a calibration curve. A) Thermogravimetric analyses of BU1, SG, a-SG, and SG-NHCO-BU1. B) UV–vis titration of K[Au(CN)2

Synthesis and characterization of a isothiouronium-calix[4]arene derivative: self-assembly and anticancer activity

• Giuseppe Granata,
• Loredana Ferreri,
• Claudia Giovanna Leotta,
• Giovanni Mario Pitari and
• Grazia Maria Letizia Consoli

Beilstein J. Org. Chem. 2025, 21, 2535–2541, doi:10.3762/bjoc.21.195

• responsiveness to conventional chemotherapy. To the best of our knowledge, calixarene derivatives have not been previously tested as anticancer agents against human renal carcinoma cells. Compound 3 suppressed the proliferation of the renal cancer cells (Figure 3) with a calculated 50% inhibitory concentration

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

• sharing structural similarity regarding N center placement showed antimicrobial activity, as measured by minimum inhibitory concentration assays. MIC values of 2–16 μM towards Gram-positive bacteria Staphylococcus epidermidis and Bacillus subtilis and 8–16 μM towards Saccharomyces cerevisiae yeast were

• bacteria Escherichia coli and Klebsiella aerogenes, and yeast Candida albicans and Saccharomyces cerevisiae was determined using minimum inhibitory concentration (MIC) assays [55][56]. As summarized in Table 4, only five of the twenty-four compounds tested displayed an ability to suppress microbial growth

• control compounds 37–42 (blue lines) in acetonitrile solvent. Synthesis of pentacyclic aromatic heterocycles from varying alkynes.a Synthesis of pentacyclic aromatic heterocycles from varying azides.a Summary of UV–vis absorbance/emission signals. Minimum inhibitory concentration assay results.a

Effect of a photoswitchable rotaxane on membrane permeabilization across lipid compositions

• Udyogi N. K. Conthagamage,
• Lilia Lopez,
• Zuliah A. Abdulsalam and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2498–2512, doi:10.3762/bjoc.21.192

• structure, and saturation, can result in different membrane mechanics, hydration, thickness, intermolecular spacing, and non-covalent interactions with the rotaxane. For example, EYPC bilayer thickness increases linearly with cholesterol concentration and can induce the formation of nanodomains [16]. Such

• S13, respectively. We investigated whether reducing the concentration of rotaxane 1 from 10 mol % to 5 mol % could provide better control over membrane changes in the more fluid bilayers, specifically in pure EYPC and EYPC/Chol 8:2 LUVs. In pure EYPC, both rotaxanes 1 and 2 induced similar levels of

• release at 5 mol % and 10 mol %, reflecting the high intrinsic permeability of this membrane and the difficulty in modulating it (Supporting Information File 1, Table S30 and Figure S21a). As expected, total release in EYPC/Chol 8:2 LUVs decreased significantly at the lower concentration of the molecules

Ex-situ generation of gaseous nitriles in two-chamber glassware for facile haloacetimidate synthesis

• Nikolai B. Akselvoll,
• Jonas T. Larsen and
• Christian M. Pedersen

Beilstein J. Org. Chem. 2025, 21, 2465–2469, doi:10.3762/bjoc.21.188

• is not easily done as the system is now under pressure. The chamber was then opened to release excess gas (on small scale) and the product in chamber B can be obtained by concentration and purification. The use of other bases than DBU, was also investigated. Similar to the synthesis of

An Fe(II)-catalyzed synthesis of spiro[indoline-3,2'-pyrrolidine] derivatives

• Elizaveta V. Gradova,
• Nikita A. Ozhegov,
• Roman O. Shcherbakov,
• Alexander G. Tkachenko,
• Larisa Y. Nesterova,
• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2025, 21, 2383–2388, doi:10.3762/bjoc.21.183

• synthesized spiro[indoline-3,2'-pyrrolidine] derivatives 4 were evaluated for antimicrobial activity via serial dilution assays across a concentration range of 0.5–1000 µg/mL. The minimum inhibitory concentration (MIC) and minimum bactericidal (fungicidal) concentration (MBC/MFC) against a diverse spectrum of

Conformational effects on iodide binding: a comparative study of flexible and rigid carbazole macrocyclic analogs

• Guang-Wei Zhang,
• Yong Zhang,
• Le Shi,
• Chuang Gao,
• Hong-Yu Li and
• Lei Xue

Beilstein J. Org. Chem. 2025, 21, 2369–2375, doi:10.3762/bjoc.21.181

• spectroscopy. Results and Discussion Partial 1H NMR spectra of PBG and WDG after binding to tetrabutylammonium iodide (TBAI) are presented in Figure 2a and 2b, respectively. All 1H NMR titrations were conducted at a fixed concentration of 8.7 mM. With the addition of 2 equivalents TBAI, the NH peak on the PBG

• shifts down by 0.1902 ppm. When the concentration was increased to 5 equivalents, the NH signal peak of carbazole continued to move towards downfield, with a displacement of 0.4004 ppm to 8.3929 ppm. When the concentration was increased to 10 equivalents, the NH signal peak of carbazole continued to move

• the acceptor. For WDG, the carbazole NH peak on WDG was shifted 0.1725 ppm downfield when 2 equivalents TBAI was added. When the concentration increased to 5 equivalents, the NH signal peak of carbazole continued to move downfield, with a displacement of 0.3649 ppm to 8.2273 ppm, while proton signals

Insoluble methylene-bridged glycoluril dimers as sequestrants for dyes

• Suvenika Perera,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 2302–2314, doi:10.3762/bjoc.21.176

• , rhodamine 6G, methyl violet 6B; 7500 rpm, 5 min for acridine orange and methylene violet), and the supernatants were analyzed by UV–vis spectroscopy. To determine the dye concentration remaining in the aqueous solutions, appropriate calibration curves were employed (Figure S12 in Supporting Information File

•  1). The removal efficiency was calculated using Equation 1, where c0 is the initial dye concentration, and ct is the dye concentration after sequestration. The results of these experiments are shown in Figure 4. Quite disappointingly, Figure 4 shows that the benzene, naphthalene, and triphenylene

• could be successfully fitted into the Langmuir isotherm model. Figure 7c shows a plot of the data fitted using Equation 2, where qe (mg g−1) represents the amount of methylene violet adsorbed at equilibrium, c (mol L−1) denotes the residual methylene violet concentration at equilibrium, and K (mol−1

Research towards selective inhibition of the CLK3 kinase

• Vinay Kumar Singh,
• Frédéric Justaud,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Blandine Baratte,
• Thomas Robert,
• Stéphane Bach,
• Chada Raji Reddy,
• Nicolas Levoin and
• René L. Grée

Beilstein J. Org. Chem. 2025, 21, 2250–2259, doi:10.3762/bjoc.21.172

• kinase activities are expressed in % of maximal activity, i.e., measured in the absence of inhibitor but with an equivalent dose of DMSO (solvent of the tested compounds). ATP concentration used in the kinase assays was 10 µM (values are means, n = 2). Kinases are from human origin (Homo sapiens) except

Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• Table 3. The preliminary ADME investigation, characterized by first-order kinetics due to low substrate concentration (≤10 µM), aids in establishing intrinsic clearance (Clint), which indicates the predicted elimination efficacy of drugs [43]. According to the generally accepted Clint ≈ 10 μL/min/kg (or

• KGaA, Darmstadt, Germany), adjusting the pH with HCl. Water for buffer and eluent preparation were provided by a Millipore Milli-Q water purification system. Kinetic aqueous solubility assay. All compounds were dissolved in DMSO to make stock solutions at 10 mM concentration. In the case of 7i, 7j, and

• (E)-9b, the highest concentration achieved in DMSO was 0.5 mM, while for (E)-9a it was 1 mM (DMSO solubility results of the compounds can be found in Supporting Information File 1). 5 μL of the stock solutions was pipetted into a 96-well plate containing 495 μL PBS (pH 6.5) in each well to achieve

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• acid (ALA), and benzylic acid (BA). These acids were oxidized and gave formaldehyde, acetaldehyde, acetone, benzaldehyde, acetophenone, and benzophenone, respectively. By increasing pH and concentration, the rate of the reactions increased, but decreased upon increasing the amount of Cl− ions (Scheme

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• and 17). The obtained diene 10a contained 13–15% of silylindene 11a as impurity. Products 10a and 11a are separable by preparative HPLC. Lowering the starting material concentration in the reaction mixture to 0.05 mmol/mL significantly decreased the diene 10a yield due to the formation of other

• in the context of 1,2-silyl shift and potential cyclization. Competing mechanistic pathways for diene 10 and indene 11 formation. Reaction scope for the synthesis of arylated tetrahydrofurans 8. Conditions: All reactions were performed on a 0.47 mmol scale. aStarting material 7d concentration: 0.1

Photochemical reduction of acylimidazolium salts

• Michael Jakob,
• Nick Bechler,
• Hassan Abdelwahab,
• Fabian Weber,
• Janos Wasternack,
• Leonardo Kleebauer,
• Jan P. Götze and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153

• followed by 1H NMR over the course of 48 h. As shown in Figure 3, at the start of the reaction, rapid consumption of the benzoylazolium starting material was observed with concomitant formation of O-benzoylated product 3. The concentration of this species then slowly decreased over the remaining reaction

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• products were obtained (see Figure 3 and Table 2). The marked improvement in product yields, compared to those observed with D1–3, may reflect the change to the workflow, i.e., variation in stock concentration to improve solubility. The diversity of the obtained products was increased by the multiple

Synthesis of N-doped chiral macrocycles by regioselective palladium-catalyzed arylation

• Shuhai Qiu and
• Junzhi Liu

Beilstein J. Org. Chem. 2025, 21, 1917–1923, doi:10.3762/bjoc.21.149

• (c) MC3. (d) Molecular arrangements of MC3. Hydrogen atoms are omitted for clarity. (a) Absorptions and (b) emissions of compounds 3a, 3b, MC1, MC2, and MC3 measured in dichloromethane at room temperature. The inset shows the photographs under UV light at 365 nm. The concentration is 10 μM

Synthesis, biological and electrochemical evaluation of glycidyl esters of phosphorus acids as potential anticancer drugs

• Almaz A. Zagidullin,
• Emil R. Bulatov,
• Mikhail N. Khrizanforov,
• Damir R. Davletshin,
• Elvina M. Gilyazova,
• Ivan A. Strelkov and
• Vasily A. Miluykov

Beilstein J. Org. Chem. 2025, 21, 1909–1916, doi:10.3762/bjoc.21.148

• glycidyl esters of phosphorus acids 1–3, their cytotoxic effects were assessed using the MTT assay on two tumor cell lines (PC-3 and MCF7) and one non-cancerous line (HSF). The assay measures the concentration of each compound required to inhibit cellular metabolic activity by 50% (IC50). All experiments

• dissolving the compounds in the culture medium to a final concentration of 25 mM. These stock solutions were stored and used for subsequent treatments. Cell treatment. 24 hours after seeding, cells were treated with the test compounds at final concentrations of 25 μM, 50 μM, 100 μM, 250 μM, 500 μM, 750 μM

• , 1,000 μM, 2,500 μM, and 5,000 μM. Each concentration was tested in triplicate. Control wells received an equivalent volume of culture medium without compounds and served as untreated negative controls. Cytotoxicity analysis of compounds. After 48 hours of treatment, MTT reagent was added to each well at

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• . Doubling the substrate concentration (Table 1, entry 7) also failed to provide a significant advantage in terms of yield, leading to the formation of the desired product in 64% yield. The replacement of both working cathode and counter anode to stainless steel electrodes caused a decrement of the yield to

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• excitation depends on the molar extinction ε of each isomer. It is the absorbance A normalised by the concentration c and the path length l, calculated according to the Beer–Lambert law: For this reason, careful choice of the excitation wavelength is important, as it affects how well one isomer can be

• of the metastable isomer [5][6][7], thus they are also important factors to consider when choosing the solvent and the concentration of the solution. The half-life can be extrapolated by monitoring the photoswitch in the metastable form over time by various spectroscopic methods (UV–vis, NMR) in the

• tautomerism is an intermolecular process that depends not only on the choice of aryl rings and substituents but also on concentration, solvent polarity, and the presence of proton sources [5][15]. In conclusion, the choice of aryl rings, substituents, and substitution position are all crucial to determine the

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• efficacy [2][3][4]. Nowadays, there are technologies that can better confine the action of drugs to where they are needed. Drug delivery is a technology that administers drugs to patients, which can specifically increase the concentration of drugs in certain parts of the body, thereby enhancing the

• nanoparticles [62]. Their morphologies mainly depend on molecular structure, concentration, and environmental properties. The cylindrical geometry of vesicles [63] promotes the arrangement of amphiphilic molecules with their hydrophobic tails pointing inward and hydrophilic heads pointing outward, forming a

• length of the alkyl chain, and the nature of the polar head group [71]. Compared with traditional surfactants, amphiphilic CAs have a lower critical micelle concentration and are more likely to self-assemble into various forms of aggregates, such as spherical micelles [72], vesicles, and spherical

Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• . Concentration under reduced pressure refers to the removal of solvent using a rotary evaporator, unless stated otherwise. All NMR spectra were obtained using a Bruker ASCEND 400 MHz spectrometer at the Nuclear Magnetic Resonance Research Resource (NMR-3, Dalhousie University). Chemical shifts (δ in ppm) for

Continuous-flow-enabled intensification in nitration processes: a review of technological developments and practical applications over the past decade

• Feng Zhou,
• Chuansong Duanmu,
• Yanxing Li,
• Jin Li,
• Haiqing Xu,
• Pan Wang and
• Kai Zhu

Beilstein J. Org. Chem. 2025, 21, 1678–1699, doi:10.3762/bjoc.21.132

• solvent and source of the active electrophilic NO2+ species. The attack of NO2+ on the nitration substrates is the rate-determining step in the nitration reaction. Therefore, the effect of sulfuric acid concentration on the nitration reaction must be considered to obtain intrinsic kinetic data, which is

• analysis can be obtained from the Mc function-correlated rate equation. The linearized equation requires prior determination of two key parameters: (i) the acidity function Mc and (ii) the concentration ratio of , to resolve the values of k* and n. According to the works of Marziano et al. [64][65][66

• ], quantitative correlations between the Mc function and both sulfuric acid concentration and temperature could be established. The values of are governed by both temperature and sulfuric acid concentration. The experimental determination of across varying temperature and H2SO4 concentrations has been widely

Synthesis of optically active folded cyclic dimers and trimers

• Ena Kumamoto,
• Kana Ogawa,
• Kazunori Okamoto and
• Yasuhiro Morisaki

Beilstein J. Org. Chem. 2025, 21, 1603–1612, doi:10.3762/bjoc.21.124

• diiodobenzene 5 using a Pd2(dba)3/PPh3/CuI catalytic system in toluene and Et3N under diluted conditions (monomer concentration = approximately 1.3 × 10−3 M) was performed. The corresponding cyclic dimer (Sp)-6 and trimer (Sp)-7 were detected mainly by thin-layer chromatography (TLC) and separated roughly using

• lifetime measurement was performed on a Hamamatsu Photonics Quantaurus-Tau fluorescence lifetime spectrometer system. Specific rotations ([α]Dt) were measured with a HORIBA SEPA-500 polarimeter: concentration “c” is g/dL. Circular dichroism (CD) spectra were recorded on a JASCO J-1500 spectropolarimeter