Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• the kinetic resolution at a concentration of approximately ten millimolar (mM) to prevent the Michael retro-Michael equilibrium from affecting the process. Keywords: 1,5-dicarbonyl; equilibrium; kinetic resolution; organocatalysis; retro-Michael; Introduction For many years, enantiomers have been

• promotes the Michael reaction, leading to the formation of the enantiomer (3R,4S) and consequently returning to the racemate. Then, we decided to investigate how concentration affects the rate and selectivity of the reaction at room temperature (Table 4). The retro-Michael reaction mainly occurs at a

• concentration of 0.17 M, producing a nearly racemic mixture of anti-1 (entries 1 and 2, Table 4). Lowering the concentration to 0.10 M slows the reaction and improves the enantiomeric ratio (entries 3 and 4, Table 4), but a nearly racemic mixture is obtained again with longer reaction times (entry 5, Table 4

Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• turn demands large volumes of solvents, negatively impacting the sustainability of light-mediated synthesis as it transitions from academic curiosity to industrial application. Moreover, since the solvent is the reaction component with the highest concentration, competitive side-reactions such as

• mechanochemistry holds potential for unique opportunities for substrate activation while adopting an environmentally benign emerging technology (Figure 2, top). For example, it is well known that molecules in the solid state (or in very high concentration) often exhibit photophysical behaviors distinct from those

• working at this interface have the potential to redefine the landscape of sustainable synthesis, with this Perspective serving as a snapshot of the current state-of-the-art. The Grotthuss–Draper, Einstein–Stark, and Beer–Lambert laws. T: transmittance; ε: molar attenuation coefficient; c: concentration; l

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• water (Figure 2A) [71][72][73], or by binding a hydrophobic substrate and holding it close to a functional(ized) rim (e.g., as in cyclodextrins) that performs a reaction (Figure 2B) [74][75][76][77][78][79]. These effects are driven mostly by effective concentration/molarity (i.e., proximity of reacting

• concentration. As for the macrocycles discussed above, dual confinement/encapsulation [36] and the hydrophobic effect dominate the origin of catalytic rate enhancements [158][159]. To avoid product inhibition, model reactions that increase molecularity (A → B + C) or that generate weakly interacting or less

Identification and removal of a cryptic impurity in pomalidomide-PEG based PROTAC

• Bingnan Wang,
• Yong Lu and
• Chuo Chen

Beilstein J. Org. Chem. 2025, 21, 407–411, doi:10.3762/bjoc.21.28

• reaction was concentration dependent, giving various amounts of 6 under otherwise the same reaction conditions. For example, at 10–30 mM wherein most of the pilot studies were conducted, the ratio of 3 and 6 could be as low as ≈1:50 by 1H NMR and ≈1:10 by MS analysis. Under these conditions, the formation

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• idea of glycosylation mechanisms to enable the readers to have a background idea as a reference before going to describe the role of protecting groups. The mechanistic pathway of glycosylation strongly depends on many factors, especially, the concentration of the participating moieties, the reaction

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• possibility of carrying out subsequent stages of research and selecting promising compounds for the further development of anticancer drugs [30]. The study showed that the IC50 inhibitory concentration of 2-(1,1-dimethyl-1H-benzo[e]indolin-2-yl)-5,6,7-trichloro-1,3-tropolone (7a) against the A431 skin cancer

Synthesis, characterization, antimicrobial, cytotoxic and carbonic anhydrase inhibition activities of multifunctional pyrazolo-1,2-benzothiazine acetamides

• Ayesha Saeed,
• Shahana Ehsan,
• Muhammad Zia-ur-Rehman,
• Erin M. Marshall,
• Sandra Loesgen,
• Abdus Saleem,
• Simone Giovannuzzi and
• Claudiu T. Supuran

Beilstein J. Org. Chem. 2025, 21, 348–357, doi:10.3762/bjoc.21.25

• inhibitory concentration, MIC90) values for compounds 7b and 7h against three different strains of Staphylococcus aureus: susceptible (ATCC 25923), methicillin-resistant (ATCC BAA-41), and multidrug-resistant (ATCC BAA-44). Table 2 shows the MIC90 values for the two halogenated compounds against different

• acetonitrile was added dropwise. Then, the reaction mixture was continued to reflux for 24 h or until the termination of the reaction. Reaction progress was monitored after intervals using TLC. On completion, filtration of the reaction mixture was performed followed by concentration under vacuum. It was then

• concentration under vacuum. It was then diluted with cold water and acidified with 5% cold HCl. The solution was allowed to stand for 15 minutes to complete precipitation. Precipitates were collected via filtration and washed with excess distilled water. The dried product was then recrystallized from absolute

Antibiofilm and cytotoxic metabolites from the entomopathogenic fungus Samsoniella aurantia

• Rita Toshe,
• Syeda J. Khalid,
• Blondelle Matio Kemkuignou,
• Esteban Charria-Girón,
• Paul Eckhardt,
• Birthe Sandargo,
• Kunlapat Nuchthien,
• J. Jennifer Luangsa-ard,
• Till Opatz,
• Hedda Schrey,
• Sherif S. Ebada and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 327–339, doi:10.3762/bjoc.21.23

• screening assays were conducted to explore their antibiofilm properties. According to the crystal violet (CV) assay, both compounds exhibited significant activity in the S. aureus biofilm inhibition assay. Farinosone A (2) (Figure 5A) displayed activity at a concentration as low as 3.9 µg/mL, resulting in

• approximately 68% inhibition of biofilm formation. Similarly, farinosone D (1) demonstrated activity up to a concentration of 15.62 µg/mL, achieving a comparable inhibitory effect of approximately 74% at this dilution. In addition, only farinosone A (2) (Figure 5B) demonstrated moderate activity in the

• preformed biofilm assay, dispersing a 24 hour preformed biofilm up to a concentration of 15.62 µg/mL with an eradication capacity of 43%. To evaluate whether the remaining biofilm biomass in the wells was metabolically active or not, a cell viability (XTT) assay was conducted after 24 hour treatment of S

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• deeper than blue light when comparing the two molar extinction coefficients of [Os(tpy)2]2+ at 450 and 740 nm for a same concentration according to the Beer–Lambert law, hence ensuring more uniform photon exposure and an improved reaction efficiency. This enhanced light penetration is reflected in the

Oxidation of [3]naphthylenes to cations and dications converts local paratropicity into global diatropicity

• Abel Cárdenas,
• Zexin Jin,
• Yong Ni,
• Jishan Wu,
• Yan Xia,
• Francisco Javier Ramírez and
• Juan Casado

Beilstein J. Org. Chem. 2025, 21, 277–285, doi:10.3762/bjoc.21.20

• +) couple. Electrolyte solutions, at a concentration 0.1 M, were prepared from anhydrous, degassed HPLC grade CH2Cl2 and anhydrous Bu4NPF6. Voltammograms were recorded at a sweep rate of 100 mV s−1. Sample concentrations were ca. 1–2 mM. Electronic spectroscopy UV–vis–NIR spectroelectrochemical studies were

• working and counter electrodes, respectively. A Ag wire was employed as the pseudo-reference electrode in a 0.1 M solution of Bu4NPF6 in freshly distilled CH2Cl2. Sample concentration was 1 mM. The spectra were collected by constant potential electrolysis, and the potentials were changed in intervals of

Synthesis and characterizations of highly luminescent 5-isopropoxybenzo[rst]pentaphene

• Islam S. Marae,
• Jingyun Tan,
• Rengo Yoshioka,
• Zakaria Ziadi,
• Eugene Khaskin,
• Serhii Vasylevskyi,
• Ryota Kabe,
• Xiushang Xu and
• Akimitsu Narita

Beilstein J. Org. Chem. 2025, 21, 270–276, doi:10.3762/bjoc.21.19

• intriguing rod-like nano- to microcrystals and/or longer wires, which were visualized by scanning electron microscopy (SEM). Results and Discussion BPP 2 could be prepared by the “DPEX” reaction [12] in 60% yield on a 0.1 g scale from dialdehyde 1 with a concentration of 0.60 mM (Table 1, entry 1). However

• , the yield of BPP decreased to 40% when the amount of 1 was increased to 1.0 g with a concentration of 2.6 mM (Table 1, entry 2). In our attempt to improve the yield of BPP 2, we decreased the equivalent of SnCl2·2H2O and increased the volume ratio of iPrOH, which unexpectedly provided BPP-OiPr 3 as a

Three-component reactions of conjugated dienes, CH acids and formaldehyde under diffusion mixing conditions

• Dmitry E. Shybanov,
• Maxim E. Kukushkin,
• Eugene V. Babaev,
• Nikolai V. Zyk and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 262–269, doi:10.3762/bjoc.21.18

• method was successfully used to generate highly active nitrile oxides and nitrilimines for 1,3-dipolar cycloaddition reactions [19][20][21]. Based on our previous experience with diffusion mixing, we assumed that formaldehyde vapor diffusion into the reaction would lead to an extremely low concentration

• placed an open small vial with a solution of the other starting compounds (Figure 1). During the reaction, formaldehyde vapors from the outer vial were slowly absorbed by the mixture in the inner vial, which ensured an extremely low concentration of CH2O and intermediates in the reaction. An alternative

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• the reaction, an attempt was made to increase the concentration, reducing the amount of solvent to 1 mL (Table 1, entry 12), product 2a was obtained in 67%, and a further reduction to 0.5 mL failed to increase the yield significantly (Table 1, entry 13). Although the amount of solvent used could have

Hydrogen-bonded macrocycle-mediated dimerization for orthogonal supramolecular polymerization

• Wentao Yu,
• Zhiyao Yang,
• Chengkan Yu,
• Xiaowei Li and
• Lihua Yuan

Beilstein J. Org. Chem. 2025, 21, 179–188, doi:10.3762/bjoc.21.10

• polymerization concentration of 17 μM. These polymers were highly concentration-dependent. Establishing this new dimerization motif with shape-persistent H-bonded macrocycles widens the scope of noncovalent building blocks for supramolecular polymers and augurs well for the future development of functional

• H1, G2, and Zn2+ with a respective concentration of 1 mM and 3 mM revealed a nanoglobular suprastructure, and a larger nanoirregular block suprastructure at higher concentration (5 mM, Figure 5). To confirm aggregate formation, 1H NMR titration experiments were carried out, in which different equiv

• addition of the macrocycle to a G2/Zn2+ complex were consistent with the formation of supramolecular polymers. The supramolecular polymers formed were further characterized by viscosity and variable-concentration NMR experiments. One important feature of supramolecular polymers is the dependency of their

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• solute concentration proved ineffective; an alternative approach was needed. Examining the van 't Hoff equation for osmotic pressure, Π = iMRT, four factors play significant roles: solute concentration M (in this case, PEG), the van 't Hoff constant i (which is 1 for non-dissociating molecules

• ), temperature T, and the ideal gas constant R. Increasing the temperature can enhance osmotic pressure, similar to solute concentration. This equation does not directly include membrane permeability as it only relates the osmotic pressure to temperature and concentration. However, membrane permeability

• indirectly affects osmotic pressure difference over the membrane. Permeability influences the concentration gradient of solute particles across the membrane [21], meaning that in this case membrane permeability affects the osmotic pressure that can be exerted on the membrane. Dehydrating polysarcosine by

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• . Using this configuration, the platform can perform a calibration of the reagent and product concentration through a standard addition method. Once the PAT is calibrated, the platform performs dynamic experiments where the concentration of the reagents is ramped to explore the parametric space. Finally

• to maximize the space–time yield (STY) while minimizing either the E-factor of the SNAr reaction or the impurity concentration of the N-benzylation reaction. For both reactions, there were four variables to optimize, including metrics for reaction time, reagent concentration, and temperature. After

Synthesis, characterization, and photophysical properties of novel 9‑phenyl-9-phosphafluorene oxide derivatives

• Shuxian Qiu,
• Duan Dong,
• Jiahui Li,
• Huiting Wen,
• Jinpeng Li,
• Yu Yang,
• Shengxian Zhai and
• Xingyuan Gao

Beilstein J. Org. Chem. 2024, 20, 3299–3305, doi:10.3762/bjoc.20.274

• ORTEP drawing obtained using the X-ray crystallographic data of 7-H. (a) UV–vis absorption spectra of the PhFlOP-based emitters 7 measured at a concentration of ≈10−5 M in toluene at room temperature. (b) UV–vis absorption spectra of 7-H measured at a concentration of ≈10−4 M in different solvents at

Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• , entry 5). Upon increasing the concentration of the PBS solution to 0.4 M, no change in yield was observed (60% yield, 100% conv.; Table 1, entry 6). Lastly, the optimal reaction time was determined to be 3 hours (67% yield, 100% conv.; Table 1, entry 7). Having optimized the reaction conditions, a scope

Efficient synthesis of fluorinated triphenylenes with enhanced arene–perfluoroarene interactions in columnar mesophases

• Yang Chen,
• Jiao He,
• Hang Lin,
• Hai-Feng Wang,
• Ping Hu,
• Bi-Qin Wang,
• Ke-Qing Zhao and
• Bertrand Donnio

Beilstein J. Org. Chem. 2024, 20, 3263–3273, doi:10.3762/bjoc.20.270

• concentration of 1 × 10−5 mol/L and in solid-state thin film. DFT calculated frontier molecular orbitals and optimized molecular structures for F1 and G11. Synthesis, yields, and nomenclature of 1,2,4-trifluoro-6,7,10,11-tetraalkoxy-3-(perfluorophenyl)triphenylene (Fn, n = 3–12) and corresponding 1,1',3,3',4,4

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• OD600 and resazurin (RSZ) metabolic assay, respectively. The final concentration of DMSO in the assays was 1% (v/v). The negative controls consisted of inoculum and 1% DMSO. The antibiotic tobramycin (Sigma-Aldrich; 16 µg/mL) was used as a positive control. The initial OD600 and final OD600 were read

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• reaction with Cs2CO3 (1.3 equiv) produced 3a in a much improved 60% yield (Table 1, entry 2). We screened other solvents and tested the impact of other inorganic bases but none of these changes improved the formation of the ylide 3a (Table 1, entries 3–6). And while increasing the reaction concentration

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• inhibitors, and their effects were investigated using the Amplex-Red® kit in C. elegans. Individuals exposed to compounds 2a, 2b, 2c, 2d, 2e, and 2f at a concentration of 1 mM were analyzed for AChE activity in their extracts. The results revealed significant inhibition of AChE levels, with compound 2e

• and 31.6 μM, respectively), which is the concentration required to double the specific luciferase reporter activity, compared to melatonin (CD = 66.4 µM). The results suggest that compounds 3a and 3b are promising as potent antioxidant therapeutic agents. Furthermore, the results of the ORAC-FL assay

• conducted at a concentration of 10 μM, with donepezil serving as a positive control. To measure their impact on cellular tau oligomerization, the fluorescence resonance energy transfer (FRET) signal intensity was quantified in a cellular tau FRET assay at the same 10 μM concentration, using MK-886, a known

Controlled oligomerization of [1.1.1]propellane through radical polarity matching: selective synthesis of SF₅- and CF₃SF₄-containing [2]staffanes

• Jón Atiba Buldt,
• Wang-Yeuk Kong,
• Yannick Kraemer,
• Masiel M. Belsuzarri,
• Ansh Hiten Patel,
• James C. Fettinger,
• Dean J. Tantillo and
• Cody Ross Pitts

Beilstein J. Org. Chem. 2024, 20, 3134–3143, doi:10.3762/bjoc.20.259

• to how favoring the path to INT2 may be achieved in practice through increasing concentration of 1. Subsequently, INT2 could abstract a Cl atom from SF5Cl via TS3 to form 2 or add to a third equiv of 1 through TS4, leading to INT3. Once again, Cl atom abstraction is thermodynamically (ΔΔG = −11.7

• here that the free energy of activation is lower for chlorination, albeit only by 0.4 kcal/mol. This is consistent with the notion that the kinetic preference can be overcome by increasing the concentration of 1 relative to CF3SF4Cl. In the second product-determining step, Cl atom abstraction by INT5

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• to Fc+) was reported to be very slow and independent of HTB concentration in the absence of 18 (H2TPP), suggesting that the porphyrin macrocycle is necessary for the O2 reduction to H2O2 (Figure 21a). From these observations, the authors concluded that O2 binding to the diprotonated form of 18 (H2TPP

• ) via NH+···O2 hydrogen bonds initiated the ORR, whereas an increase in the HTB concentration inhibited the ORR by blocking NH+ binding sites for O2. Further, the role of the proton source on ORR was confirmed by testing a stronger acid, TFA: in this case, the O2 reduction rate is decreased to almost

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• = 20,000), revealing that the average number of penetrated CDs could be controlled from 3 to 125 (theoretical maximum was 227) by adjusting the concentration ratio of α-CD to PEG, the reaction temperature, and the end-capping method (Scheme 4B) [65]. Concurrently, in 2007, Jouini and co-workers reported

• of 8 shaped two CD rings movable along the polymer main chains. Thus, the applied stress can be distributed to the entire material by the movement of the crosslinking points to avoid a stress concentration, leading to a higher toughness than the conventional materials. Since a lot of existing review