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

Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives

• Loris Geminiani,
• Kathrin Junge,
• Matthias Beller and
• Jean-François Soulé

Beilstein J. Org. Chem. 2025, 21, 2234–2242, doi:10.3762/bjoc.21.170

• the presence of water, highlighting its robustness. Keywords: azo compounds; cross-coupling; domino catalysis; palladium; phosphine ligands; Introduction Azobenzenes are a widely studied class of compounds known for their distinctive photoresponsive properties, rendering them valuable in a variety

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

• File 1, Figures S1–S3). Based on their calculated physicochemical properties, all compounds satisfied Lipinski’s Rule of Five suggested by Wager et al. [34] (molecular weight < 500 Da, logP < 5, number of hydrogen-bond donors < 5, number of hydrogen-bond acceptors < 10) [35], and the topological polar

• regarding their physicochemical and ADME parameters. Based on literature analogy with related compounds, furthermore on calculated properties, and results from kinetic solubility, in vitro membrane permeability and metabolic stability measurements, a tetracyclic derivative, 2,4-dimethyl-2,7,8,9,10,11

A m-quaterphenyl probe for absolute configurational assignments of primary and secondary amines

• Yuka Takeuchi,
• Mutsumi Kobayashi,
• Yuuka Gotoh,
• Mari Ikeda,
• Yoichi Habata,
• Tomohiko Shirai and
• Shunsuke Kuwahara

Beilstein J. Org. Chem. 2025, 21, 2211–2219, doi:10.3762/bjoc.21.168

• Shibazono, Narashino, Chiba 275-0023, Japan Research Center for Materials with Integrated Properties, Toho University, 2-2-1 Miyama, Funabashi, Chiba 274-8510, Japan 10.3762/bjoc.21.168 Abstract We report a method for determining the absolute configurations of chiral amino alcohols, amino acid esters, and

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• organic synthesis [1][2][3][4][5][6][7][8][9][10][11][12][13][14] but also are critical moieties in natural products [15][16][17][18], organic materials [19] and pharmaceuticals [20][21][22][23][24] due to their unique chemical, electrical, optical, pharmacological and biological properties. Gracilioether

• search tools and profiles applied. Review Construction of indoles Indoles, exhibiting interesting photoelectric properties and biological activities, were widely applied in organic synthesis, pharmacology and organic materials science [112][113][114][115][116][117][118][119][120][121][122][123][124][125

• properties and wide applications. Alkynes were extensively used as starting materials or intermediates for the synthesis of five-membered rings. Recently, the electrochemical synthesis of organic five-membered rings from alkynes have been developed due to the superiorities of electrochemical transformations

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

• . Polylactic acid (PLA) and polyglycolic acid (PGA) are most important examples of biopolymers exhibiting interesting biodegradability properties [41]. The co-polymerization of PLA with glycolic acid was reported by Ayyoob and Kim [42]. High molecular weight poly-lactic-co-glycolic acid (PLGA) was obtained by

• ][87][88][89][90][91][92]. Essayem and co-workers reported the conversion of DHA with the help of TiO2-based catalysts having dual properties. Two parallel pathways are as follows: on one hand the catalyst Lewis acidic sites promote the formation of pyruvaldehyde and lactic acid (LA) by a two-step

• introduction of substituents to the seven-methine carbon chain of Cy7 influences its optical properties and ability to interact with biomolecules. A one-pot synthesis of γ-acyloxy-Cy7 from renewable furfural, simple anhydrides, and a quaternary ammonium salt under smooth conditions was reported (Scheme 63

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• quaternary centers isolated from Penicillium cylopium and exhibit various biological properties [68]. The intriguing structure and interesting biological properties have attracted continued synthetic attention [69][70][71]. In a 2023 report, the group of Lee and Han adopted an early-stage desymmetric

Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design

• Daniil V. Khabarov,
• Valeria A. Litvinova,
• Lyubov G. Dezhenkova,
• Dmitry N. Kaluzhny,
• Alexander S. Tikhomirov and
• Andrey E. Shchekotikhin

Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161

• Street, Moscow 11991, Russia 10.3762/bjoc.21.161 Abstract Indolo[1,2-c]quinazoline derivatives have emerged as promising chemotype in drug discovery due to their versatile biological activities, including antimicrobial and antiviral properties. In this study, we report the design, synthesis, and

• systematic analysis of biological properties of indolo[1,2-c]quinazoline derivatives remains to be unexplored. Up to date, only limited results were presented. Rohini et al. have revealed antimicrobial potential in 6-substituted indolo[1,2-c]quinazoline derivatives (Figure 1, top) [15][16]. A series of

• electrophilic reagents. This site offers a strategic handle for introducing diverse substituents to modulate the compound's properties. Although the indolo[1,2-c]quinazolin-6(5H)-one scaffold offers considerable potential for structural diversification, current literature describes only the arylation at

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• studies of these molecules indicated that they exhibit a broad-spectrum activities including antifungal, insecticidal, plant pathogenic properties and phytotoxic activity. Structurally, these molecules basically contain an isocoumarin ring system and a five-carbon side chain. The side chain could further

• ingredients of these plants, and have elucidated a huge number of lignan natural products with novel structural backbones [32][33][34][35] (Scheme 5a). Biologically, the gymnothelignans exhibit a broad-spectrum of properties such as antiviral, antifungal, and insecticidal activities. Structurally