Switchable pathways of multicomponent heterocyclizations of 5-amino-1,2,4-triazoles with salicylaldehydes and pyruvic acid

• Yana I. Sakhno,
• Oleksander V. Buravov,
• Kostyantyn Yu. Yurkov,
• Anastasia Yu. Andryushchenko,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2030–2035, doi:10.3762/bjoc.21.158

• control of the reaction, while oxygen-bridged heterocycles 4 are formed under thermodynamic control. The purity and structure of compounds 4 and 5 were established by elemental analysis, mass spectrometry, 1H and 13C NMR spectroscopy, and X-ray diffraction study (Figure 1). For example, the 1H NMR spectra

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

• spectrum also indicating the presence of significant amounts of the imidazolium salt IMeH+ (characteristic C2–H signal at δ = 8.94 ppm; 28%) and benzoate species (BzO−, ortho-C–H signals at δ = 7.98 ppm; 50%). To confirm the photocatalytic nature of the novel carbonyl reduction process, a series of control

• higher reduction potential of this comparatively electron-rich compound. Purification of the crude reaction mixture from 1 by column chromatography allowed for the isolation of pure product 5 as a colorless oil in 59% yield. A control reaction performed under the same conditions in the dark resulted only

Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization

• Miao Xiao,
• Liuyang Pu,
• Qiaoli Shang,
• Lei Zhu and
• Jun Huang

Beilstein J. Org. Chem. 2025, 21, 1964–1972, doi:10.3762/bjoc.21.152

• that control many essential biological processes in animals and humans [1][2][3][4]. In particular, prostaglandin D2 (PGD2, 3) is a key pathophysiological mediator in a number of human diseases and biological pathways, such as systemic mastocytosis and inflammation. Therefore, the development of

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• enantioselective desymmetrization of prochiral 1,3-diols within complex structures can be realized using organometallic catalysts composed of copper or zinc salts and different types of chiral ligands. In general, the ability to control the stereoselectivity of the product by using the enantiomer of the ligand in

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

• acquiring the control LSV of HSA, 10 µL of each alkylating agent was introduced separately into the albumin solution. As soon as the alkylating agent was added, the characteristic oxidation wave of the albumin nearly vanished or became drastically reduced. Control experiments confirmed that compounds 1–3

• , 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

• measured at 590 nm using an Infinite M200 microplate reader (Tecan, Switzerland). Cell viability was calculated relative to the untreated control (set at 100%). Data were processed and analyzed using GraphPad Prism 10 software. Electrochemistry. Linear sweep voltammograms were recorded using a BASi Epsilon

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

• co-workers [44], the presence of a strong protic acid, such as methanesulfonic acid, MsOH, is essential to promote the intramolecular coupling. A control experiment revealed that when the electroreduction of 1a was performed in the absence of MsOH (Table 1, entry 3), no formation of the desired

• precedents involving electroreduction of activated imines and diiminium species [19]. Furthermore, control experiments conducted in the absence of methanesulfonic acid (Table 1, entry 3) resulted in no observable product formation, highlighting the acid activation in driving this transformation. Cyclic

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

• novel inherently chiral ligands have been explored. For example, they demonstrated excellent enantioselectivity control in some asymmetric reactions, such as the Rh/diphosphine ligand 66-catalyzed asymmetric addition reaction between cyclic enone and arylboronic acid. In 2024, our group reported the

• diverse catalytic abilities, precise stereoselectivity control and mild reaction conditions. In this Review, we systematically summarized the advancements in the CPA-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules. Various CPA-catalyzed reactions, such

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

• protocol, a set of control experiments was conducted to gain insight into the reaction mechanism, as depicted in Scheme 4. To clarify the significance of oxidative conditions, the standard reaction was initially conducted under an inert atmosphere by replacing oxygen with nitrogen (reaction 1). Under these

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

• -controlled, diffusion-controlled, osmotic-controlled (which encompasses osmotic pressure and swelling control), chemically controlled, nanoparticle systems, and supramolecular controlled-release systems. Among these, supramolecular controlled-release systems have advantages such as dynamic adjustability

• , stimulus responsiveness, specific recognition and binding, and multi-target synergistic action [14][15][16]. These characteristics enable precise control of drug release and targeted drug delivery, thereby improving drug stability and bioavailability, and reducing drug toxicity and side effects

• domain of drug-controlled release. This article mainly reviews the supramolecular drug delivery systems constructed from aromatic macrocycles (Figure 1). These systems achieve intelligent control over drug release through reasonable manipulation of stimuli, including external factors such as pH, light

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• applications. The assembly of nonreducing 1,1′-linked disaccharides presents greater challenges than conventional chemical glycosylation due to the need for simultaneous control of stereochemistry at two anomeric centers. The structural complexity of natural biomolecules entailing 1,1′-disaccharides, which

• synthesis of neotrehalosamines related to the sugar moiety of the nucleoside antibiotic tunicamycin was performed using benzoylated 2-(benzoyloxyimino)-protected GlcN bromide donor 5, which enabled 1,2-cis stereochemical control through the non-participating C-2 benzoyloxyimino group, leading to the

• '-neotrehalosamines 7 and 9, respectively (Scheme 1) [38]. The stereochemical outcome was found to be independent of the initial anomeric configuration of the N-phthalimido-protected lactol acceptor, which was explained by kinetic control and a rapid anomerization in favor of the β-anomer [50]. The applicability of

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

• tubular, continuous tank, bubbling and injection nitration reactor – directly governs thermodynamic control, product distribution, process scalability, and quality assurance [4][5]. Batch systems remain prevalent for low-throughput fine chemicals due to their operational flexibility, whereas continuous

• -flow configurations demonstrate superior safety and efficiency. While the synthetic significance of nitration is underscored by the broad utility of nitro derivatives, persistent technical challenges including regioselectivity control, over-nitration phenomena, and substrate oxidation side reactions

• reactors. For intensely exothermic nitration reactions with rapid kinetics, this technology enables uniform mixing, efficient heat removal, and precise control of critical parameters including reaction temperature and reactant stoichiometry. Crucially, continuous operation permits scalable production of

Structural analysis of stereoselective galactose pyruvylation toward the synthesis of bacterial capsular polysaccharides

• Tsun-Yi Chiang,
• Mei-Huei Lin,
• Chun-Wei Chang,
• Jinq-Chyi Lee and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2025, 21, 1671–1677, doi:10.3762/bjoc.21.131

• biomolecules in organisms. However, the R/S stereochemistry of pyruvate ketal is difficult to control through chemical methods. In this study, the acid-labile pyruvate ketal linked to the 4- and 6-positions of galactose was cautiously constructed, and the X-ray analysis of the R-configured product was

Influence of the cation in hypophosphite-mediated catalyst-free reductive amination

• Natalia Lebedeva,
• Fedor Kliuev,
• Olesya Zvereva,
• Klim Biriukov,
• Evgeniya Podyacheva,
• Maria Godovikova,
• Oleg I. Afanasyev and
• Denis Chusov

Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130

• , the synthesis of the remedy for Parkinson’s disease, piribedil (9), in high yield (80%) demonstrated the practical utility of the elaborated synthetic method (Figure 1). To get insight into the mechanism of the developed approach the reaction mixtures were thoroughly analyzed and several control

• reaction medium, thereby preventing their reduction. This fact and the result of the control experiment where Schiff base was used as a starting material (Scheme 3a) demonstrated that Schiff base was not an intermediate in the developed reaction. The reactions between carbonyl compounds and secondary

• amines proceeded forming products in moderate to high yields. In this process enamine can be the intermediate. Therefore, enamine was tested in the control experiment and the corresponding product was obtained in moderate yield (49%). To validate the experiment with enamine the reductive amination with

pH-Controlled isomerization kinetics of ortho-disubstituted benzamidines: E/Z isomerism and axial chirality

• Ryota Kimura,
• Satoshi Ichikawa and
• Akira Katsuyama

Beilstein J. Org. Chem. 2025, 21, 1568–1576, doi:10.3762/bjoc.21.120

• barriers by protonation, providing a novel approach to control the kinetics of isomerization via pH adjustment. The results showed that protonation of the amidine moiety significantly suppresses both C–N bond rotation and C–N/C–C concerted rotation, demonstrating the potential of ortho-disubstituted

• triggered by protonation and deprotonation [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. This class of molecules has the capacity to regulate three-dimensional structures and motions of molecules through simple acid–base stimuli. This provides a high degree of control over their

• of molecules that can precisely control the range of pH to which they can respond. Furthermore, it is also important to discover new molecular skeletons, as there is a lack of variation in the substructures that act as pH-responsive molecular switches. Previously, we reported that chalcogen

Facile synthesis of hydantoin/1,2,4-oxadiazoline spiro-compounds via 1,3-dipolar cycloaddition of nitrile oxides to 5-iminohydantoins

• Juliana V. Petrova,
• Varvara T. Tkachenko,
• Victor A. Tafeenko,
• Anna S. Pestretsova,
• Vadim S. Pokrovsky,
• Maxim E. Kukushkin and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 1552–1560, doi:10.3762/bjoc.21.118

• compounds in two-fold serial (50–100 μM) dilutions. Only DMSO + PBS (phosphate-buffered saline) was used as a control, since the studied compounds were soluble only in DMSO. Cell viability was measured using the standard MTT test [42]. Absorbance was measured at 540 nm using a Multiskan™ FC microplate

Azide–alkyne cycloaddition (click) reaction in biomass-derived solvent Cyrene^TM under one-pot conditions

• Zoltán Medgyesi and
• László T. Mika

Beilstein J. Org. Chem. 2025, 21, 1544–1551, doi:10.3762/bjoc.21.117

• -triazoles in a less toxic and recyclable medium could further control and reduce the environmental impacts of this synthetically very important transformation. Herein, we report a study on the copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reaction in CyreneTM under mild conditions. Results and

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• while 3-iodochromone failed to provide the desired enaminone 9a (Table S7, Supporting Information File 1). Control experiments including the reaction in the absence of visible-light or photocatalyst, showed no product formation (Table 1, entries 16 and 17). Interestingly, the yield of 9a dropped to 30

Azobenzene protonation as a tool for temperature sensing

• Antti Siiskonen,
• Sami Vesamäki and
• Arri Priimagi

Beilstein J. Org. Chem. 2025, 21, 1528–1534, doi:10.3762/bjoc.21.115

• different azo compounds [23][24][25]. More recent work has harnessed protonation to enable red-light switching [12][13][26] and to control the stability of the cis-isomer [27][28][29]. These studies have focused on how protonation affects isomerization, with less attention given on how external stimuli

• influence ion-pairing strength, offering a strategy to further control the protonation behavior and enhance the temperature-sensing performance. With improved understanding of azobenzene–acid interactions and good agreement between computations and experiments, a design-driven approach to temperature

Calcium waste as a catalyst in the transesterification for demanding esters: scalability perspective

• Anton N. Potorochenko and
• Konstantin S. Rodygin

Beilstein J. Org. Chem. 2025, 21, 1520–1527, doi:10.3762/bjoc.21.114

• linoleic acid (57.2%). Additional control experiments were performed with the original carbide slag (CS25) and commercial CaO, Ca(OH)2 and CaCO3 to confirm the main catalyst phase (CaO) as catalytically active species in the reaction and the results of the control experiments are summarized in Table 1

• . Reaction conditions: oil to alcohol molar ratio = 1:12, 1 wt % CS600, 65 °C, 2 h. Control experiments on the example of transesterification of soybean oil with methanol.a Supporting Information Supporting Information File 2: General information, experimental procedures, characterization data, and copies

Highly distinguishable isomeric states of a tripodal arylazopyrazole derivative on graphite through electron/hole-induced switching at ambient conditions

• Himani Malik,
• Sudha Devi,
• Debapriya Gupta,
• Ankit Kumar Gaur,
• Sugumar Venkataramani and
• Thiruvancheril G. Gopakumar

Beilstein J. Org. Chem. 2025, 21, 1496–1507, doi:10.3762/bjoc.21.112

• were subjected to control AFM experiments to check for any contamination or impurities on the surface. We also note that no traces of ethanol remained on the surface after pumping, as confirmed by AFM images. Instrumentation All AFM and STM measurements were performed using an Agilent 5500 in soft

Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

• . Finally, control experiments without irradiation gave only traces of the benzamide 2aa showing no activation by the Ru complex at room temperature (Table 1, entry 24). An experiment conducted under an air atmosphere yielded only 9% of 2aa (Table 1, entry 25) indicating that the presence of atmospheric

• reactivity pattern in the current transformation, a reaction mechanism was proposed taking into the account the known data and control experiments (Scheme 4). Upon irradiation with blue light, the Ru(II) catalyst undergoes photoexcitation, followed by an oxidative single-electron transfer (SET) process with

• the iodonium salt, leading to the generation of an aryl radical, aryl iodide, and Ru(III). The formation of the aryl radical was corroborated through a trapping experiment utilizing TEMPO as a radical scavenger (Scheme 4 and Supporting Information File 1, 5. Control experiments, Figure S18). The

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

• illustrating how subtle atomic substitutions can significantly influence the conformational stability of helical molecules (Table 19). These studies illustrate how precise heteroatom modulation enables fine control over CPL directionality and emission lifetimes, offering promising avenues for the development

N-Salicyl-amino acid derivatives with antiparasitic activity from Pseudomonas sp. UIAU-6B

• Joy E. Rajakulendran,
• Emmanuel Tope Oluwabusola,
• Michela Cerone,
• Terry K. Smith,
• Olusoji O. Adebisi,
• Adefolalu Adedotun,
• Gagan Preet,
• Sylvia Soldatou,
• Hai Deng,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2025, 21, 1388–1396, doi:10.3762/bjoc.21.103

• cell line are given below), after which the Alamar Blue cell viability reporter was added and the fluorescence recorded using an FLx 800 plate reader (BioTek) with excitation wavelength 535/540 nm and emission wavelength at 590/610 nm using Gen5 Reader Control 2.0 Software (BioTek). EC50 values were

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• reactions were carried out at ambient pressure (control) and under HHP (up to 3.8 kbar) conditions. These representative reactions provided higher yields for the products and HHP enabled truly green processes that are catalyst- and solvent-free, to occur with high yields and producing only non-toxic by

• , thus the actual reaction mixture remains in a liquid state, making it ideal for HHP-assisted reactions. The first reaction in the optimization effort was the control experiment at atmospheric pressure. Under these conditions, no product formation was observed even after 10 h reaction time. However, 8

• parentheses. As shown in Table 4 and Scheme 4, the HHP reactions occurred at 50 °C with low to moderate yields, and with nearly quantitative yields at 80 °C. HHP reactions afforded the products in higher yields than those of the control experiments under the same conditions (time, temp. etc.) but only at 1

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• loadings were necessary for ortho-substituted phenyls. Control experiments and DFT calculations revealed that the oxetane ring is formed before the tetrahydrofuran in the domino process. In 2023, Shigehisa and co-workers published a new cycloisomerisation strategy for the construction of oxetane rings from

• after deprotonation of a suitably functionalised ether at the α-carbon. Therefore, a stabilising group must be incorporated to control regioselectivity of the deprotonation as well as to increase the acidity of the α-hydrogen. Mordini et al. showed that even weakly stabilising groups such as phenyl

• still runs smoothly, if the aryl is substituted for cyclohexyl. The proposed mechanism, supported by control experiments, deuterium exchange studies and energy calculations, consists of the following steps: conjugate addition of the carbene to the allenoate, regioselective addition of the resulting