Highly electrophilic, gem- and spiro-activated trichloromethylnitrocyclopropanes: synthesis and structure

• Ilia A. Pilipenko,
• Mikhail V. Grigoriev,
• Olga Yu. Ozerova,
• Igor A. Litvinov,
• Darya V. Spiridonova,
• Aleksander V. Vasilyev and
• Sergey V. Makarenko

Beilstein J. Org. Chem. 2026, 22, 123–130, doi:10.3762/bjoc.22.5

• biologically active properties. Thus, barbamide exhibits molluscicidal activity [7], and sintokamide A is active against prostate cancer [8] (Figure 1). As derivatives of strained and unique structure and properties [9][10] cyclopropanes are of interest for entering into various transformations along the path

• groups seems attractive for both theoretical chemistry and the synthesis of 2-aminocyclopropanecarboxylic acids, of which representatives have biologically active properties against kynurenine-3-monooxygenase [25] and GABA receptors [26]. Such aminocyclopropane derivatives can be classified as donor

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

• sustained interest from synthetic chemists worldwide due to their pronounced antibacterial and anticancer properties. Since their discovery, bis-THIQ scaffolds have been constructed primarily through the Pictet–Spengler reaction, a cyclization strategy that continues to be widely employed in total synthesis

Advances in Zr-mediated radical transformations and applications to total synthesis

• Hiroshige Ogawa and
• Hugh Nakamura

Beilstein J. Org. Chem. 2026, 22, 71–87, doi:10.3762/bjoc.22.3

• properties [1]. Among its notable physical attributes is its high corrosion resistance: metallic zirconium is exceptionally stable toward acids and bases at ambient temperature and is less susceptible to corrosion than titanium. Its low toxicity and excellent biocompatibility have historically supported the

• available materials, in benzene afforded the Zr(RCNN)2 complex 18. Investigation of the photoredox properties of the synthesized complex revealed trends similar to those of known photosensitizers, suggesting its potential utility as a photosensitizer [15]. Accordingly, the Zr(MeCNN)2 complex was employed as

• widely employed in the field of organic synthesis. This widespread use is underpinned by zirconium’s abundance in the Earth’s crust and its low toxicity, among other advantageous properties. Traditionally, its applications have predominantly involved two-electron processes via hydrozirconation. In recent

Reactivity umpolung of the cycloheptatriene core in hexa(methoxycarbonyl)cycloheptatriene

• Dmitry N. Platonov,
• Alexander Yu. Belyy,
• Rinat F. Salikov,
• Kirill S. Erokhin and
• Yury V. Tomilov

Beilstein J. Org. Chem. 2026, 22, 64–70, doi:10.3762/bjoc.22.2

• , the antiaromatic properties of anion 2 [21] allow to regard these reactions as one of those driven by the relief of antiaromaticity [22][23][24][25][26][27]. Results and Discussion In our previous work [21], we demonstrated that most cycloheptatrienyl anions prefer conformers distorted to an allylic

Sustainable electrochemical synthesis of aliphatic nitro-NNO-azoxy compounds employing ammonium dinitramide and their in vitro evaluation as potential nitric oxide donors and fungicides

• Alexander S. Budnikov,
• Nikita E. Leonov,
• Michael S. Klenov,
• Andrey A. Kulikov,
• Igor B. Krylov,
• Timofey A. Kudryashev,
• Aleksandr M. Churakov,
• Alexander O. Terent’ev and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2025, 21, 2739–2754, doi:10.3762/bjoc.21.211

• , structures, and redox properties, effective synthetic strategies for the construction of N–N and N–O systems remain markedly underdeveloped. Unlike traditional methods for constructing C–C and C–Het bonds, the number of methods for selective N–N [1][5][19][20][21][22][23][24][25][26][27][28][29] and N–O [30

• Griess test results, all synthesized nitro-NNO-azoxy compounds released high fluxes of NO (36–137%) exceeding those of CAS-1609 (22.1%) and NG (15.3%). Interestingly, azoxy derivatives 2a–e,i showed NO-donor properties only in the presence of ʟ-cysteine proposing the thiol-dependent mechanism of NO

• release. At the same time, compounds 2f–h demonstrated moderate NO-donor properties in the absence of ʟ-cysteine, which can be associated with a more complex mechanism of NO release for these substances. Importantly, azoxy species 3f and 4f showed no difference in NO-donor properties irrespective of the

Competitive cyclization of ethyl trifluoroacetoacetate and methyl ketones with 1,3-diamino-2-propanol into hydrogenated oxazolo- and pyrimido-condensed pyridones

• Svetlana O. Kushch,
• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess,
• Pavel A. Slepukhin,
• Alexandrina S. Volobueva,
• Vladimir V. Zarubaev and
• Victor I. Saloutin

Beilstein J. Org. Chem. 2025, 21, 2716–2729, doi:10.3762/bjoc.21.209

• to be obtained in one stage using commercially available reagents [1][2][3]. Their ambident properties make 3-oxo esters convenient reagents for the use in multicomponent syntheses, with the Hantzsch [4][5] and Biginelli [6][7][8] reactions being the best known. In the transformations, 3-oxo esters

• the one hand, owing to the fact that the pyridine framework is widespread among natural compounds [40][41], and, on the other hand, because of the unique properties of fluorine [42][43][44][45]. In this work, 1,3-diaminopropan-2-ol (3) has for the first time been introduced into the reaction of ethyl

• biological properties of the synthesized compounds. We focused primarily on their potential antiviral activity, since a moderate anti-influenza effect of the related octahydropyrido[1,2-a]pyrimidinones was previously revealed [24]. The series of bicycles 4att, 4a–dct, 4atc, 4acc, 5ctc were tested against

Tandem hydrothiocyanation/cyclization of CF₃-iminopropargyl alcohols with NaSCN in the presence of AcOH

• Ruslan S. Shulgin,
• Ol’ga G. Volostnykh,
• Anton V. Stepanov,
• Igor’ A. Ushakov,
• Alexander V. Vashchenko and
• Olesya A. Shemyakina

Beilstein J. Org. Chem. 2025, 21, 2694–2702, doi:10.3762/bjoc.21.207

• motif in various biologically active molecules and materials due to its unique physical, chemical, and biological properties [28][29][30]. SCN and trifluoromethyl groups have proved to be versatile moieties in the design and development of numerous active pharmaceutical ingredients, agrochemicals, drugs

Synthesis of new tetra- and pentacyclic, methylenedioxy- and ethylenedioxy-substituted derivatives of the dibenzo[c,f][1,2]thiazepine ring system

• Gábor Berecz,
• András Dancsó,
• Mária Tóthné Lauritz,
• Loránd Kiss,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2645–2656, doi:10.3762/bjoc.21.205

• 100 μL platinum pan in 25 mL/min nitrogen atmosphere. Melting properties of the amorphous samples (21b, 38d, 54f) were also studied by a TA Instruments Discovery DSC differential scanning calorimeter in the 25–120 °C temperature range with a 10 °C/min heating rate using 2.5 to 3.0 mg sample in a

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

• compounds 3n and 4n was carried out using torsion angle analysis and 13C NMR chemical shift calculations to evaluate the absence of expected signals in the NMR spectra of these compounds. Their photophysical properties were also assessed, confirming a preference for a fluorescence mechanism via an ICT

• available drugs [1]. These structures exhibit unique properties that influence pharmacokinetic and pharmacodynamic parameters, including lipophilicity, polarity, hydrogen-bonding capacity, and toxicological profiles [2][3][4]. Among them, five-membered multi-heterocyclic (FMMH) rings are privileged

• ], antioxidant [34], cytotoxic [35], and antiproliferative [36]. The structures of these compounds allow the synthesis of a large collection of bioactive molecules due to their nucleophilic and electrophilic properties [37]. One of the forms of modifications is at the methylene group, particularly in the 5

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

• properties (3). Given their unique structural features and pharmacological potential, segetalins have become important targets for both synthetic chemistry and drug development. However, efficient and general synthetic routes to access this family have remained limited over the past decades. Previous

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• products continue to attract considerable research interest due to their intricate chemical architectures and distinctive biological properties. Through decades of dedicated effort, synthetic chemists have accomplished the total synthesis of several members within this family that share a common core

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

• , there remains a wide range of chemical space representing these heterocycles that has not yet been explored. Hence, there is an ongoing interest in identifying synthetic strategies to access unreported ring structures and in characterizing the resulting physical and biological properties of such

• 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

• physical and biological properties of such polycyclic aromatic heterocycles would serve as an initial evaluation of their potential use in chemical, material, and therapeutic applications. Results and Discussion The two-step approach used to prepare the target pentacyclic aromatic heterocycles 13–18 via

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

• photochemical process occurs, which triggers the release from only the vesicles containing EYPC. These findings underscore the significance of both the physical and chemical properties of the bilayer in enabling effective light-triggered cargo release through rotaxane activation. Keywords: lipid membrane

• proteins that are responsible for essential cellular functions [1]. As a result, the function and properties of lipid membranes are significantly influenced by their lipid composition, which varies across various domains of life, including mammalian, prokaryotic, and plant cells, and even between

• bacteria or malignant cells like cancer) [5][6], or to influence membrane protein function and thereby control cellular behavior [7][8]. One promising approach is the development of light-activated molecules that can modulate membrane properties upon irradiation, enabling remote activation with high

Palladium-catalyzed regioselective C1-selective nitration of carbazoles

• Vikash Kumar,
• Jyothis Dharaniyedath,
• Aiswarya T P,
• Sk Ariyan,
• Chitrothu Venkatesh and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2025, 21, 2479–2488, doi:10.3762/bjoc.21.190

• functionalization of carbazoles via C–H activation [48][49][50][51][52][53][54][55][56][57][58][59][60][61]. Among the variously substituted carbazole scaffolds, nitro-substituted carbazoles exhibit a diverse range of medicinal properties and serve as key starting materials for the synthesis of bioactive compounds

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

• trifluoroacetonitrile [24]. Schmidt published the first synthesis of glycosyl trifluoroacetimidates and concluded that their glycosyl-donor properties were similar to the trichloroacetimidates, but more difficult to prepare and purify [24]. In contrast to these observations, Nakajima et al. reported the

The intramolecular stabilizing effects of O-benzoyl substituents as a driving force of the acid-promoted pyranoside-into-furanoside rearrangement

• Alexey G. Gerbst,
• Sofya P. Nikogosova,
• Darya A. Rastrepaeva,
• Dmitry A. Argunov,
• Vadim B. Krylov and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2025, 21, 2456–2464, doi:10.3762/bjoc.21.187

• preferable while for the α-isomers the preference is for the pyranoside. Again, for the phenyl β-ᴅ-galactosides the DLPNO-CCSD(T) approach predicted prevalence of the furanoside form. However, phenyl group differs from methyl in electronic properties and in size. We suppose that these differences may cause

Catalytic enantioselective synthesis of selenium-containing atropisomers via C–Se bond formations

• Qi-Sen Gao,
• Zheng-Wei Wei and
• Zhi-Min Chen

Beilstein J. Org. Chem. 2025, 21, 2447–2455, doi:10.3762/bjoc.21.186

• ]. Selenium is a non-metallic element, but compared with sulfur of the same main group, selenium has a larger atomic radius, smaller electronegativity, and exhibits certain metallic properties. Due to the special physical and chemical properties of selenium between metal and nonmetal, selenium not only has

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• objects for investigating the possibility of using them in the synthesis of compounds of iridoid topology. Iridoids belong to the class of terpenoids and are secondary metabolites of plants, as well as multi-tasking objects [5][17][18]. Studies on the pharmacological properties of iridoids have shown

• ) (Scheme 20). Indanes (benzocyclopentanes) and their derivatives are widely used in materials science and nanotechnology and have important biological properties such as anti-allergic, antitumor, anticonvulsive, antihypercholesteremic, herbicidal, fungicidal and antimicrobial activity [60]. In [58], a

• the study of inflammatory diseases and other bioactive properties. Epoxidation of 230 with m-chloroperoxybenzoic acid (m-CPBA) gave the epoxide 231. Subsequent addition of excess BF3·OEt2 led to a semipinacol rearrangement, affording 232 in 65% yield as a single diastereomer. The aldehyde 232 was then

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• , toxicity, pesticide similarity, and biodegradability of methyl laurate in comparison with a series of conventional organic solvents, water, some fatty acids and their derivatives. The findings of this investigation revealed that methyl laurate exhibited better green solvent properties when evaluated

• of these solvents have been observed to degrade under conditions that are particularly severe [20]. For instance, although ionic liquids are well-known green solvent alternatives with superior properties compared to conventional organic solvents, their recovery from the reaction medium can be quite

• formation of the five-membered isoxazolidine ring motif, which displays a range of biologically active properties [26][27][28][29][30]. It is notable that the fused pyrrolo-isoxazolidines represent a particularly versatile class of heterocyclic compounds and intermediates, which have been demonstrated to

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

• bioactive molecules (Figure 1). This scaffold exhibits a broad range of pharmacological activities, including significant in vitro antimycobacterial properties [4], potent antitumor effects against melanoma cell lines [5], and antagonism of TH2 lymphocyte function [6]. Due to their wide-ranging biological

• protocol highlights its potential for further derivatization and the discovery of valuable properties. Natural and synthetic bioactive spiro[indoline-3,2'-pyrrolidine] derivatives. Previous approaches and our work. The reaction of 2-arylindoles 1 with α,β-unsaturated ketones 2. aIsolated yield of the 5

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

• ) and WDG (rigid fluorene backbone), were synthesized via Friedel–Crafts reactions. Their iodide (I−) recognition properties were systematically explored using 1H NMR, UV–vis absorption, and fluorescence spectroscopy. Quantitative analysis via the Benesi–Hildebrand equation and nonlinear fitting

• variations in fluorescence properties, leading to deviations from the linear Stern–Volmer relationship governing the quenching mechanism. The flexible benzene ring of the PBG allows the cavity to be conformationally adjusted to fit the size of I−, while the rigid fluorenyl group of the WDG results in steric

Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• for precise control over their structural, dynamic, and functional properties. By harnessing light as a non-invasive stimulus with high spatial and temporal resolution, these photoswitches allow for the modulation of the rotaxanes’ intra- and intermolecular interactions, optoelectronic properties, and

• azobenzene serves as a recognition site for an α-cyclodextrin macrocycle [22]. This material demonstrated remarkable mechanical properties, including a rupture strain of 2800%, which was attributed to the stress-dispersive sliding motion of the rotaxane cross-links. Moreover, the polymeric network exhibits

• –guest interaction induces a chiral signal, while the azobenzene chromophore imparts photoswitching properties to the molecule. Furthermore, solvent-mediated hydrogen-bonding interactions tailored within the inner cyclodextrin cavity, combined with photocontrolled isomerization of the azo moiety, enable

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

• reactive dyes from textile wastewater streams [27][28][29]. More recently, our group has synthesized water-soluble acyclic cucurbit[n]urils (e.g., M1, Figure 1) and demonstrated that they retain the essential molecular recognition properties of macrocyclic CB[n] [30]. Acyclic CB[n] are more easily

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• lactone 26. The Zhang group has extended the chiral metalloradical catalysis to cyclopropanation by the intermolecular reaction between styrenes and ketodiazoacetates [59]. Cyclopropanes were obtained in good yields with high relative and absolute stereocontrol. Properties, such as relatively high earth

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

• could be further derivatized (e.g., via borylation, epoxidation), establishing a versatile platform for accessing fused-ring natural products. Substituent-controlled cyclization of 1,n-enynes In transition metal-catalyzed cyclization reactions, the electronic properties and steric hindrance of

• reaction. Catalyst-controlled cyclization of 1,n-enynes The core function of a catalyst lies in providing a new, energetically more favorable pathway for the reaction. Different catalytic systems, with their unique physical structures, chemical compositions, and electronic properties, could form distinct