Knoevenagel condensation of 4,5- and 1,8-diazafluorenes

• Darya S. Cheshkina,
• Christina S. Becker,
• Alina A. Sonina and
• Maxim S. Kazantsev

Beilstein J. Org. Chem. 2026, 22, 803–812, doi:10.3762/bjoc.22.62

• to the iminium cation occurs via the methylene carbon of the corresponding enamine tautomeric form 1B or 2B. Thus, this process is limited by the concentration of this form which is expected to be higher for 1,8-diazafluorene (2) due to the activation by the neighboring nitrogen atoms via the

• mesomeric effect. On the other hand, diazafluorenes are potentially capable of reversible protonation by acetic acid, which is a competing process decreasing the equilibrium concentration of the enamine form (Scheme 2). Furthermore, an electrostatic repulsion between the protonated diazafluorene (1A/1A’ or

Synthetic study of vic-bromination of diarylacetylenes, easy purification and separation

• Akane Togo,
• Hiyono Suzuki,
• Yuto Akai,
• Makoto Matsumoto,
• Yoshinori Suzuma,
• Hidehiko Kodama and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2026, 22, 795–802, doi:10.3762/bjoc.22.61

• brine (20 mL), and dried over Na2SO4. After this, filtration and concentration were performed; the organic phase was passed through a short column of silica gel using CH2Cl2 (100 mL) to remove inorganic materials and others; then it was concentrated under reduced pressure to give the crude product. This

Halogenated azobenzene acrylates: from efficient solution photoswitching to stable solid-state photochromic materials

• Martina Vachtlová,
• Michaela Fecková,
• Vítězslav Zima,
• Jan Podlesný,
• Milan Klikar,
• Oldřich Pytela,
• Patrik Pařík,
• Jakub Opršal,
• Eliška Juhaňáková,
• Veronika Chrtová and
• Filip Bureš

Beilstein J. Org. Chem. 2026, 22, 782–794, doi:10.3762/bjoc.22.60

• the E-isomers as compared to the Z-isomers. Linear optical properties Fundamental optical properties of the target azobenzenes 1a–f in solution were investigated by electronic absorption spectra at 20 °C in DCE at a concentration of 4 × 10−5 M. The absorption maxima for both isomers (λE/Zmax) and the

Design, synthesis, and biological evaluation of FXR/ASK1 dual-target modulators

• Xi Zhang,
• Jingyan Wang,
• Ziqiang Zhao,
• Caiyi Wang,
• Zenghui Ye,
• Wei-Yuan Ma,
• Jian-Xing Xu and
• Fengzhi Zhang

Beilstein J. Org. Chem. 2026, 22, 771–781, doi:10.3762/bjoc.22.59

• -luciferase reporter gene assay. As demonstrated in Figure 1, among the designed dual-target modulators, compounds Z8, Z11, Z17, and Z30 exhibited the most potent effects at a concentration of 10 μM. ASK1 Inhibition The inhibitory activity against ASK1 was evaluated using the ADP-Glo™ kinase assay. A screen

• of the designed dual-target modulators identified 17 compounds that inhibited ASK1 (Figure 2). Among the compounds examined, Z8 demonstrated the greatest potency, exhibiting an inhibition rate of 84.59% at a concentration of 10 μM. Lipid-modifying activity In light of the prevalence of the reduction

Synthesis and biological evaluation of new brassinosteroid analogs with C-22 benzoate function

• María Núñez,
• Camila Escobar,
• Mario Párraga,
• Mauricio Soto,
• Luis Espinoza-Catalán,
• Katy Díaz and
• Andrés F. Olea

Beilstein J. Org. Chem. 2026, 22, 753–762, doi:10.3762/bjoc.22.57

• inhibition of root and hypocotyl elongation in Arabidopsis thaliana seedlings, among other bioassays. The results show that for the same BRs, the measured effects vary with the bioassay and concentration. For example, in the RLIT the growing effect increases with increasing concentration, whereas on root

• growth BRs act as root growth promoter at low concentration and the opposite effect is observed at high concentrations [22]. As sensing of BRs by BRI1 is the starting point of the mechanism by which plant responses are produced, this binding process has been extensively studied and it has been shown that

• regions, causing laminar inclination in a concentration-dependent manner. Although the molecular mechanism of this phenomenon remains elusive [35][36], this bioassay has been used with a large number of BR analogs and the obtained results have allowed the establishment of structure–activity relationships

Rongalite addition to dienones: diastereoselectivity in cyclic sulfone synthesis; stereochemical rationalization and prospects as a general conjugate nucleophile

• Melina Goga,
• Hao Zong,
• James Franco,
• Jazmine Prana,
• Rudolph Michel,
• Antonia Muro,
• Elana Rubin,
• Janet Brenya,
• Henk Eshuis and
• Magnus W. P. Bebbington

Beilstein J. Org. Chem. 2026, 22, 742–752, doi:10.3762/bjoc.22.56

• high concentration of ≈80% acetic acid (pH ≈3), it seemed plausible that activation of the dienone carbonyl group would occur by hydrogen-bonding, rather than complete proton transfer to the carbonyl oxygen lone pairs [29]. We therefore included explicit solvation with acetic acid in our computational

Anti-invasive and cytotoxic evaluation of a (+)-pinoresinol-based semisynthetic library against glioblastoma

• Chen Zhang,
• Kah Yean Lum,
• Jonathan M. White,
• Paul I. Forster,
• Nicholas Booth,
• Sunita A. Ramesh and
• Rohan A. Davis

Beilstein J. Org. Chem. 2026, 22, 691–704, doi:10.3762/bjoc.22.54

• (MIC = 25 µM), and Malassezia furfur (MIC = 12.5 µM) [20]; antioxidant activity with the inhibition of CuSO4-induced peroxidation of low-density lipoprotein in a concentration-dependent manner from 0.1−10 µM [21], and anti-invasiveness activity on HT115 human colon cancer cells at a concentration

• evaluations of (+)-pinoresinol (2) and its analogues 3–7 against the U251MG cell line, compound (+)-4,4'-di(3,3-dimethylbutanoyl)pinoresinol (6) showed slight cytotoxicity (19% cell viability reduction) at a concentration of 10 µM. Also, on the KNS42 cell line, only (+)-4,4'-di(3,3-dimethylbutanoyl

• concentration of 1 µM with a treatment time of 5 h, and only (+)-4,4'-di(3,3-dimethylbutanoyl)pinoresinol (6) reduced the invasion of the cells (by ≈50%) when compared to the vehicle control. None of the other compounds tested reduced the invasive capability of the cells (Figure 7A). Based on the results of the

Photoorganocatalytic trifluoromethylation of (het)arenes in green conditions

• Egor N. Boronin,
• Svetlana E. Kaurkina,
• Milena M. Svetlakova,
• Anton S. Bolshakov,
• Maxim V. Arsenyev,
• Vasilii F. Otvagin,
• Alexey Yu. Fedorov,
• Timothy Noël and
• Alexander V. Nyuchev

Beilstein J. Org. Chem. 2026, 22, 662–671, doi:10.3762/bjoc.22.50

• , entries 4 and 5). The influence of catalyst loading was then examined. Raising the photocatalyst concentration to 2 mol % led to yields of 64%, 64%, and 78% under white, violet, and blue light, respectively (Table 1, entries 3–5). A further increase to 5 mol % (Table 1, entry 5) afforded 87% yield

Advantages of PROTACs in achieving selective degradation of homologous protein families

• Luxi Yang,
• Xinfei Mao,
• Jingyi Zhang,
• Jing Shu,
• Wenhai Huang,
• Xiaowu Dong,
• Yinqiao Chen and
• Mingfei Wu

Beilstein J. Org. Chem. 2026, 22, 628–661, doi:10.3762/bjoc.22.49

• , could induce the degradation of CDK4 and CDK6 in MDA-MB-231 cells. Its DC50 (concentration of 50% protein degradation) was 13 and 34 nmol/L, respectively. That is, compound 5 has a more pronounced ability to degrade CDK4 than CDK6. The same year, Rao, Wu et al. published their work on the design of

• p38 isoforms (β and γ) were not degraded when the concentration was up to 2.5 µM. On the contrary, PROTACs with the long linker in the "phenyl series" showed almost no ability to degrade the p38 subtype (30, 31, 32, 33, Figure 12). When the linker length in the "phenyl series" was reduced to 10 atoms

• degradation selectivity of PROTACs. For example, compound 28 shows submicromolar degradation of two p38 subtypes. Once the linker contains an additional carbon atom, the resulting PROTAC 29 degrades p38α at a nanomolar concentration and p38δ at a micromolar concentration. Similarly, the 10-atom-linker

Towards the targeted protein degradation of CK2: design and synthesis of CAM4066-based PROTACs

• Sophie Day-Riley,
• Sona Krajcovicova,
• Aryaman Raj Sokhal,
• Jan L. Venne,
• Paul Brear,
• Marko Hyvönen,
• Benjamin C. Whitehurst,
• Jason S. Carroll and
• David R. Spring

Beilstein J. Org. Chem. 2026, 22, 611–619, doi:10.3762/bjoc.22.47

• CK2α′ under these conditions was observed, as indicated by unchanged band intensities relative to controls. At the highest concentration (10 μM), PROTAC 24 caused a loss of both CK2α and vinculin bands, suggesting cytotoxicity rather than target-specific degradation. The two CRBN-based PROTACs 28 and

Design and synthesis of an erdafitinib-based selective FGFR2 degrader

• Yumeng Jin,
• Shidong Wang,
• Sihan Pan,
• Shuqi Huang,
• Weichen Zhou,
• Xiaohao Huang,
• Lei Zheng and
• Lingfeng Chen

Beilstein J. Org. Chem. 2026, 22, 583–591, doi:10.3762/bjoc.22.44

• a half-maximal degrading concentration (DC50) of 121.4 nM, and this effect exhibited time- and concentration-dependence. Assessed at the cellular level, LC-JD-6 has a half-maximal inhibitory concentration in the KATO III (IC50) of 96.0 nM and showed low inhibitory activity in normal cells

• gastric cancer cells. Although LC-JD-5, which is the homoisomer of LC-JD-6, is still lacking compared to LC-JD-6. To further verify the potency, LC-JD-6 was prescribed at an extensive concentration range (0.4–10,00 nM) in KATO III cells after 6 hours, with the DC50 of 121.4 nM and a maximal degradation

Get a better glimpse on sequential photoreactions of trisnorbornadienes with ¹⁹F NMR spectroscopy

• Julian Felix Maria Hebborn,
• Ben Eric Merten,
• Thomas Paululat and
• Heiko Ihmels

Beilstein J. Org. Chem. 2026, 22, 527–534, doi:10.3762/bjoc.22.38

• , that is, from monoquadricyclane 2f2,1 to bisquadricyclane 2f1,2 and eventually the trisquadricyclane 2f0,3. The latter was only formed after a sufficient concentration of the intermediates was present (5 min). From this point onwards, the fraction of the starting material 1f and the intermediates 2f2,1

Synthesis and uranyl(VI) extraction performance of a calix[4]pyrrole–tetrahydroxamic acid receptor

• Sara Karnib,
• Rana Baydoun,
• Wissam Zaidan,
• Nancy AlHaddad,
• Omar El Samad,
• Bilal Nsouli,
• Francine Cazier-Dennin and
• Pierre-Edouard Danjou

Beilstein J. Org. Chem. 2026, 22, 486–494, doi:10.3762/bjoc.22.36

• from the decrease in activity concentration. It is important to note that the extraction efficiency of PCP HA was evaluated based solely on the quantification of 238U. Uranium is a naturally occurring radionuclide that exists predominantly as a mixture of three isotopes: 238U, 235U and 234U. Among

Synthesis of a HDAC inhibitor–nanogold probe for cryo-EM visualization in class I HDAC co-repressor complexes

• Wiktoria A. Pytel,
• John W. R. Schwabe and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2026, 22, 480–485, doi:10.3762/bjoc.22.35

• , followed by centrifugation (see Supporting Information File 1 for full details). The resulting Au–(CI-994) conjugate was concentrated to a final volume of 1 mL. The concentration of Au–(CI-994) was determined by UV–vis spectroscopy, using absorbance at 420 nm – a characteristic wavelength for nanogold [19

• ]. Based on the Beer–Lambert law, the concentration was calculated to be 2.69 μM. Attempts at further concentration led to precipitation, indicating limited solubility at higher concentrations. The HDAC inhibitor–nanogold probe inhibits HDAC enzymatic activity in the CoREST complex We first wanted to

• nanogold particle (Au–NH2). Left: Single point concentration HDAC assay. Concentration of Au–NH2 and Au–(CI-994) = 0.54 µM. Concentration of CI-994 = 20 µM. Right: Dose response inhibition of HDAC activity in the CoREST complex with Au–(CI-994). Boc-(Ac)Lys-AMC substrate = 100 µM; CoREST complex = 12.5 nM

Structural reassignment of compound 968, an allosteric glutaminase inhibitor

• Lindsey A. Albertelli,
• Sainabou Jallow,
• Chun Li and
• Scott M. Ulrich

Beilstein J. Org. Chem. 2026, 22, 455–460, doi:10.3762/bjoc.22.33

• cloned into pQE80 were grown at 37 °C overnight in LB supplemented with 100 µg/mL ampicillin. These cultures were diluted 1:100 into 2 L of LB media supplemented with 100 µg/mL ampicillin and grown at 37 °C with shaking at 225 rpm until the OD600 reached 0.6. IPTG was added to a final concentration of

• 9.4), NAD+ (2 mM), glutamate dehydrogenase (1 µL of a 50% glycerol solution, 15 mg/mL), and hydrazine (0.5 µL) and incubated at room temperature for 40 min. The absorbance at 340 nm was measured and converted to glutamate concentration using the extinction coefficient for NADH of 6220 M−1 cm−1. The

Synthesis and anti-cancer activity of naphthalimide–organylselanyl conjugates

• Rajkumar Ravi and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2026, 22, 416–435, doi:10.3762/bjoc.22.29

• concentration of 2 × 10−5 M, as shown in Supporting Information File 1, Figure S21. Both compounds have slightly similar absorption bands. Compound 7 shows an absorption maximum at 395 nm as a broad band peak. In comparison to compound 7, compound 8 displays a slight bathochromic (red) shift, with absorption

• compounds exhibited significant, dose-dependent cytotoxicity, with cell viability decreasing as the concentration increased. Notably, both compounds demonstrated comparable cytotoxic effects against the tested cancer cell line. To assess the significance of variations between concentration and cell

• viability, one-way ANOVA was performed using GraphPad Prism software [64], as shown in Figure 8, comparing the control group to each test concentration of the compound 7 (Figure 8a) and compound 8 (Figure 8b). The results showed no significant differences between the control and 6.12 µM concentrations

Cone p-aminocalix[4]arenes enriched with ‘clickable’ alkyne or azide functionalities

• Ilia Korniltsev,
• Vasily Bazhenov,
• Alexander Gorbunov,
• Dmitry Cheshkov,
• Stanislav Bezzubov,
• Vladimir Kovalev and
• Ivan Vatsouro

Beilstein J. Org. Chem. 2026, 22, 399–415, doi:10.3762/bjoc.22.28

• spectra. Upon tuning the reaction conditions, it was found that a more complete nitration of calixarene 6 along with some suppression of the undesired side reactions could be achieved by decreasing the nitric acid excess (to ≈10 equiv per calixarene aromatic unit) and its concentration in dichloromethane

• (to ≈1 M), reducing the content of acetic acid in the mixture (to 1 mol per mol of HNO3) and extending the room-temperature reaction time to 72 h. Yet, under these conditions, the desired calix[4]arene 11 was obtained in only 31% yield (Scheme 2), and further variations in reagent excess/concentration

• conditions. In line with this, compounds 8–10 having less sterically hindered narrow-rim substitution patterns were found to be more resistant to side reactions during wide-rim nitration as well as to the target exhaustive nitration itself. These reactions required a higher nitric acid concentration of ≈2.5

Design, synthesis and biological evaluation of 2,5-diaryloxazolo[4,5-d]pyrimidin-7-ylamines as selective cytotoxic agents against HeLa cells

• Maryna V. Kachaeva,
• Agnieszka B. Olejniczak,
• Marta Denel-Bobrowska,
• Victor V. Zhirnov,
• Yevheniia S. Velihina,
• Stepan G. Pilyo and
• Volodymyr S. Brovarets

Beilstein J. Org. Chem. 2026, 22, 390–398, doi:10.3762/bjoc.22.27

• antiproliferative and cytotoxic activity against the tested NCI60 cancer cell lines. Also, several other 7-(1,4-diazepan)- and 7-piperazine-substituted [1,3]oxazolo[4,5-d]pyrimidines (structures A and B in Scheme 1) showed cytotoxic activity in the micromolar concentration range against most breast cancer cell

• cells. Therefore, regardless of the concentration in effect, the compound with greater selectivity should be favored. According to this criterion, compounds 1, 7, and 9 show the most significant appeal for further testing as potential agents against cervical cancer. Unfortunately, none of these

• of 670 nm was measured in an ELISA reader (VarioskanLux, Thermo Scientific) and CC50 (50% cytotoxic concentration) was calculated. ADMET analysis Available online web sites of an integrated online platform for Windows: ADMETlab 3.0 [24] and Deep-PK [25] were applied to explore ADMET properties of the

Spirobarbiturates with a pyrrolizidine moiety: synthesis, structure and biological evaluation

• Arthur A. Puzyrkov,
• Andrew S. Drachuk,
• Ekaterina A. Popova,
• Alexander V. Stepakov and
• Vitali M. Boitsov

Beilstein J. Org. Chem. 2026, 22, 274–288, doi:10.3762/bjoc.22.20

• compounds against human cervical carcinoma (HeLa), erythroleukemia (K562), and melanoma (Sk-mel-2) cell lines. It was found that the studied spiro-fused adducts reduced the cell proliferation in a time- and concentration-dependent manner. The results of these investigations for 24 h and 72 h are presented

• tryptanthrin, 11H-benzo[4,5]imidazo[1,2-a]indol-11-one or indolin-2-one instead of the barbituric moiety [58][59][60]. The most interesting effect however, was the increased Sk-mel-2 cell viability under treatment with compounds 4f and 4g at the lowest concentration tested (5 µg/mL). Actin cytoskeleton changes

Configuration–packing synergy enabling integrated crystalline-state RTP and amorphous-state TADF

• Ruiyan Wang and
• Yunan Wu

Beilstein J. Org. Chem. 2026, 22, 224–236, doi:10.3762/bjoc.22.16

• tetrahydrofuran (THF) solution at a concentration of 1.0 × 10−5 M, the steady-state fluorescence spectrum of 1 was recorded, and its phosphorescence spectrum was subsequently measured at a temperature of 77 K to investigate its low-temperature behavior (Figure 3). Following the established spectroscopic

• carbonate (K2CO3) with a concentration of 1 g/mL (3 mL) was added. Subsequently, tetrakis(triphenylphosphine)palladium(0) (0.07 g, 0.06 mmol) was introduced to the reaction mixture to promote the coupling reaction. The mixture was then heated to reflux and maintained at this temperature for an overnight

Synthesis of diaryl phosphates using phytic acid as a phosphorus source

• Kazuya Asao,
• Seika Matsumoto,
• Haruka Mori,
• Riku Yoshimura,
• Takeshi Sasaki,
• Naoya Hirata,
• Yasuyuki Hayakawa and
• Shin-ichi Kawaguchi

Beilstein J. Org. Chem. 2026, 22, 213–223, doi:10.3762/bjoc.22.15

• potassium peroxodisulfate aqueous solution (4.0 w/v %, 5 mL) was added to the diluted phytic acid solution (25 mL), and the resulting mixture was autoclaved (121 °C, 30 min). Thereafter, the solution was diluted with deionized water to a concentration of approximately 1 µg P/mL. Step 3 (measurements): The

• total P concentration was measured via absorption spectrophotometry. The coloring agent (2 mL) was added to the diluted samples (25 mL), thoroughly mixed, and left for 15 min. After 15 min, the absorbance of each sample was measured at 880 nm using a V-650 spectrophotometer (JASCO, Tokyo, Japan). A

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

• incubated at 37 °C for 24 hours. Bacterial growth was assessed by measuring turbidity at 550 nm using a spectrophotometer. The MIC was defined as the lowest concentration of the test compound that inhibited ≥90% of bacterial growth relative to the control (no compound). Structures of streptoquinolines A (1

Improved synthesis and physicochemical characterization of the selective serotonin 2A receptor agonist 25CN-NBOH

• Adrian G. Rossebø,
• Hannah G. Kolberg,
• Anders E. Tønder,
• Louise Kjaerulff,
• Poul Erik Hansen,
• Karla A. Frydenvang,
• Jesper Østergaard and
• Jesper L. Kristensen

Beilstein J. Org. Chem. 2026, 22, 175–184, doi:10.3762/bjoc.22.11

• sufficient for most biological applications given the high potency of the compound both in vitro and in vivo [6]. Here, we show that if solutions with a higher concentration are needed, pure water could be considered. According to HPLC analysis, 1·HCl was found to be stable in solution in phosphate buffer at

• aqueous solutions of 1·HCl may be prepared and stored well in advance of any application or investigation. Subsequently, the apparent pKa values (concentration-based) for 1 were determined to be 8.4 ± 0.1 and 10.7 ± 0.1 for the protonated amine and phenol, respectively, and the calculated pH-dependent

• h in a temperature-controlled incubator at 25 °C. The concentration of 1 in the buffer solution before and after partitioning, ci and cw, respectively, was determined by HPLC, from which distribution coefficients, D, were calculated according to where Vw and Vo are the volume of the buffer solution

Symmetrical D–π–A–π–D indanone dyes: a new design for nonlinear optics and cyanide detection

• Ergin Keleş,
• Alberto Barsella,
• Nurgül Seferoğlu,
• Zeynel Seferoğlu and
• Burcu Aydıner

Beilstein J. Org. Chem. 2026, 22, 131–142, doi:10.3762/bjoc.22.6

• −, signals of 2b protons have completely disappeared, and the protons of the new species become apparent. An increase in cyanide concentration did not cause any further changes in spectra. This result indicates that cyanide gives a mono-addition to the vinyl group (Scheme 2). DFT results To further confirm

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• caliche deposits in Chile [2]. This concentration of supply raises potential concerns regarding long-term availability and geopolitical vulnerability. Recent interest in alkenyl chlorides has been driven by their occurrence in bioactive natural products (Figure 1) [3][4][5], pharmaceuticals (Figure 2) [6