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

• multiple tautomers (Scheme 7a) [37][39]. Relative stability of these tautomers is ranked as follows: 2-i > 2-ii > 2-iii > 2-iv > 2-v [74][75][76]. Therefore, compounds 3n and 4n may exist in equilibrium, with the enolic form being slightly more stable, which could explain the unusual behavior in their NMR

• through intramolecular hydrogen bonding. By comparing the data for λabs and λem, it is evident that the compounds exhibit significant Stokes shifts with values above 2,100 cm−1, reflecting their stability in the excited state [87][88][89]. The highest values of Stokes shifts were observed in polar protic

• , protonation of these compounds resulted in a lowering of the HOMO energy level, leading to an increase in the HOMO–LUMO gap and, consequently, greater molecular stability. In contrast, deprotonation led to an increase in the LUMO energy level, with little influence on the HOMO energy. Notably, the neutral

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

• stability of intramolecular hydrogen bonds in the peptide backbone, thereby promoting the formation of stable secondary structures (such as α-helices or β-sheets) in cyclic peptides. Spectra acquired in H2O, 0.01×PBS, and 30% TFE (Table S1, Supporting Information File 1) demonstrate: (i) definitive β-sheet

• signatures (217 nm minima) in 1, 3, 4; (ii) enhanced β-sheet stability from constrained macrocycles in 2, 7, 8, 10; (iii) universal α-helix induction by TFE in 1–10, with 5 and 6 retaining helicity in aqueous buffers. Conclusion We have developed an efficient and reliable solid-phase synthesis strategy for

Silica gel with covalently attached bambusuril macrocycle for dicyanoaurate sorption from water

• Michaela Šusterová and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2025, 21, 2604–2611, doi:10.3762/bjoc.21.201

• competing dicyanoargentate(I) anions. We also examine the recyclability of the material and assess its stability in organic solvents, comparing its performance with that of a previously developed material containing noncovalently bound bambusuril. Keywords: anion binding; anion extraction; anion receptor

• report a new material, SG-NHCO-BU1, in which the BU1 macrocycle is covalently grafted onto the surface of silica gel. We demonstrate that this hybrid material can be used for the selective dicyanoaurate(I) sorption from water. Moreover, it is shown that unlike SG-BnBU, SG-NHCO-BU1 exhibits good stability

• minimal decomposition at temperatures below 800 °C as confirmed by the analysis. In contrast, a-SG, SG-NHCO-BU1, and SG-BU1 exhibited reduced thermal stability due to the presence of organic substituents (Figure 1A and Supporting Information File 1, Figure S1C). A weight loss of 10% for BU1, SG-NHCO-BU1

Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• equivalents, which is crucial in dual or triple catalytic cycles. The electron-rich carbene center facilitates faster SET processes in photocatalytic reactions. Triazolium-based NHCs exhibit higher oxidative and photochemical stability, making them well-suited for visible-light-driven catalytic

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

• atmosphere significantly suppressed side reactions, yielding the cyclized product in excellent yield and selectivity. This indicates that N-formylsaccharin, beyond acting as a CO-releasing agent, may function as a ligand in the catalytic cycle to regulate the palladium catalyst’s activity and stability

Synthesis and characterization of a isothiouronium-calix[4]arene derivative: self-assembly and anticancer activity

• Giuseppe Granata,
• Loredana Ferreri,
• Claudia Giovanna Leotta,
• Giovanni Mario Pitari and
• Grazia Maria Letizia Consoli

Beilstein J. Org. Chem. 2025, 21, 2535–2541, doi:10.3762/bjoc.21.195

• , it is generally accepted that values higher than ±40 mV are associated with strong stability by repulsion, preventing further aggregation phenomena. Cytotoxicity and cancer cell selectivity Thiouronium-containing molecules can inhibit cancer cells, inducing apoptosis or necrosis, by different

Isoorotamide-based peptide nucleic acid nucleobases with extended linkers aimed at distal base recognition of adenosine in double helical RNA

• Grant D. Walby,
• Brandon R. Tessier,
• Tristan L. Mabee,
• Jennah M. Hoke,
• Hallie M. Bleam,
• Angelina Giglio-Tos,
• Emily E. Harding,
• Vladislavs Baskevics,
• Martins Katkevics,
• Eriks Rozners and
• James A. MacKay

Beilstein J. Org. Chem. 2025, 21, 2513–2523, doi:10.3762/bjoc.21.193

• nucleobases that showed enhanced triplex stability through cooperative effects compared to the control thymine base. In a follow up study, the pendant amide was removed from the Io core to determine the importance of the third hydrogen bond. To our surprise, these second-generation Io derivatives retained

• phenomenon was observed previously with V and this design element was intentionally incorporated with an expectation toward aiding in triplex stability [33]. For Db1, calculations reveal that the intended H-bond between the cationic –NH2+– moiety did in fact form (ca. 2.1 Å, Figure 7A). However, the distal

• stabilizing H-bond but rather formed a hydrogen bond with the U in the U–A base pair (ca. 2.2 Å, Figure 7B). This interaction resulted in pushing the entire residue towards the RNA backbone where the Io base could further bind to a phosphate which likely explains why Db2 shows the lowest triplex stability of

Assembly strategy for thieno[3,2-b]thiophenes via a disulfide intermediate derived from 3-nitrothiophene-2,5-dicarboxylate

• Roman A. Irgashev

Beilstein J. Org. Chem. 2025, 21, 2489–2497, doi:10.3762/bjoc.21.191

• visible region, and improved morphological stability [4][5][6]. Recent reports have shown that the development of alkyl-supported TT-based semiconductors has led to high-performance, air-stable OFETs [7], while integration of TT frameworks into donor–acceptor architectures has enabled the development of

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

• , as described by Schmidt [24]. The acetylated glucosyl trifluoroacetimidate 4 was synthesized in 66% yield (Figure 2). The slightly higher isolated yield is reflecting the higher stability of the product and hence an easier purification. The two-chamber method clearly works for the generation of

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

• multiple stereocenters, including contiguous quaternary carbons. As a result, the carboborative ring contraction reaction is conveniently used for structural modification of natural products containing a cyclohexene ring and in the synthesis of new compounds to increase their activity, metabolic stability

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

• criteria (availability, price, recyclability, grade, synthesis, toxicity, biodegradability, performance, stability, flammability, storage, renewability) with a view to defining the concept of green solvents [71]. Methyl laurate, predicted as the main potential green solvent in this study, fulfils almost

• solvent in a wide range of organic reactions that necessitate elevated temperatures. Furthermore, the oxidative stability index of methyl laurate at temperatures of 80 °C and 110 °C is greater than 40 (h), and the oxidation onset temperature is 198.5 °C which is better than those of methyl oleate [105

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

• interplay between conformational selection and induced-fit mechanisms in isomeric systems remains underexplored. Cram’s preorganization theory [13] posits that prestructured hosts with minimized solvation exhibit enhanced binding stability. Recent advances [14][15][16] highlight the pivotal role of

• synergistic binding mechanism driven by cavity complementarity, and the energy of the PBG–iodide complex is lower than that of the WDG–iodide complex, it indicates that PBG forms a thermodynamically more stable complex with iodide ions compared to WDG. This stability difference arises from the distinct

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

• -stilbenes have 5-membered rings fused to the carbon–carbon double bond, are more photostable, and undergo reversible photoisomerization with higher efficiency (Figure 2) [75]. Notably, their cis isomer exhibits higher thermal stability than that of other commonly used photoswitches, such as azobenzene. This

• . However, most photoswitchable rotaxanes developed to date have been designed for use in organic solvents or non-biological environments. To fully harness their potential in biomedical and biotechnological settings, it is essential to establish new design principles that ensure biocompatibility, stability

• motion of [2]rotaxane based on a stiff-stilbene photoswitch. Figure 13 was reproduced with permission of The Royal Society of Chemistry, from [81] (“Toward bidirectional photoswitchable colored photochromic molecules with visible light stability” by T.-G. Zhan et al., Chem. Commun., vol. 54, issue 67

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• sofosbuvir (2). Fluorination at C2 in the nucleoside results in metabolic stability and resistance to hydrolysis as it destabilizes the formation of a C1 oxocarbenium ion [5][6]. Trifluoromethylated γ-butyrolactones also find applications as antiviral agents, for example, lactone 4 which has activity against

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

• confirmed that the cyclization pathways were controlled by the influence of substituents on the stability of the intermediates. This work expanded the scope of gold-catalyzed reactions through systematic cycloisomerization studies of 1,6-enynes and an ethyl 4-oxocyclohexanecarboxylate-derived 1,7-enyne. In

• , whereas internal alkynes favored the 8-endo-dig pathway due to steric constraints and carbocation stability. This strategy facilitated efficient and selective synthesis of macrocyclic amines, with precise ring size control via substituent modulation. In 2021, Liu group reported a BiCl3-mediated

• ligands could enhance catalytic activity and efficiency while enabling fine control over chemo-, regio-, stereo-, and enantioselectivity of reactions. Ligands enhance both the thermal/chemical stability and solubility profiles of catalysts in specific reaction media. Thus, ligands function as a regulatory

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

• metabolic stability of the most promising derivatives was also determined using human liver microsomes. Keywords: early ADME characterization; Fischer indole cyclization; heterocycles; indoles; lead-likeness; new ring systems; physicochemical characterization; Introduction Considering the published

• physicochemical characterization, we conducted standardized metabolic stability assessments on pooled human liver microsome (HLM) isolates of the primary and secondary lead compounds identified during the solubility and permeability studies. The measured values are summarized in the last column of Table 2 and

• 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

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

• of levulinic acid-derived molecules. The same group later reported a more active heterogeneous catalyst, Ru–MnOx/Al2O3, providing 2-butanol with yields up to 98.8% [242]. Conversion to 2-methyltetrahydrofuran: 2-Methyltetrahydrofuran is a promising biofuel with high energy density, high stability and

Solar thermal fuels: azobenzene as a cyclic photon–heat transduction platform

• Jie Yan,
• Shaodong Sun,
• Minghao Wang and
• Si Wu

Beilstein J. Org. Chem. 2025, 21, 2036–2047, doi:10.3762/bjoc.21.159

• [35][36][37][38][39][40][41]. Notably, the utilization of azobenzene-based materials in solar thermal storage applications is gaining considerable attention due to their advantages in low synthesis cost, facile molecular design, exceptional cycling stability, and superior fatigue resistance [6][8

• transition behavior, achieving high gravimetric energy densities (300–400 J/g) with long-term storage stability (Figure 6d). Grossman and Durgun proposed methods for incorporating azobenzenes into macrocyclic structures [82]. Their computational models indicated that the molecular rings connecting the

• -molecule azobenzene derivatives achieve gravimetric energy densities of 300–400 J/g with long-term storage stability. However, solvent dependence or steric hindrance in multiazobenzene units remains an inherent challenge dictated by material type. These materials show promising applications in device

Synthesis of N-doped chiral macrocycles by regioselective palladium-catalyzed arylation

• Shuhai Qiu and
• Junzhi Liu

Beilstein J. Org. Chem. 2025, 21, 1917–1923, doi:10.3762/bjoc.21.149

• rings. In the molecular arrangement, a pair of enantiomers exists in each cell for MC3 (Figure 2d). Considering the C–C single bonds between the π-subunits, isomerization among different molecular configurations might occur via rotations. To further investigate the conformational stability of MC3

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

• terminal aromatic rings [17]. Despite lacking asymmetric stereogenic centers, this nonplanar scaffold exhibits intrinsic P/M chirality due to the helical arrangement of the π-extended skeleton. Renowned for their high thermal stability and structural rigidity, chiral helicenes have emerged as prominent

• conducted a thorough evaluation of the stability of the helical chirality across the synthesized quinohelicenes, indicating a high racemization barrier. In 2024, our group further extended the CPA-catalyzed sequential Povarov reaction and aromatization strategy by using 2-vinylphenols 14 as the olefin

• , thermal stability studies demonstrated high configurational stability of these planarly chiral macrocycles, a critical feature that enhances their potential for future utility. In 2023, Zhao and co-worker reported the asymmetric synthesis of planarly chiral paracyclophanes through either catalytic kinetic

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• conjugated with the chromophore structure, will influence its absorption spectrum and stability [4]. The solvent will also affect the properties, as it can stabilise or destabilise either the ground or the excited state, resulting in a red- or blue shift of the spectra. The thermal half-life (t1/2) measures

• strongly overlapped, resulting in a less efficient switching. Conversely, di-ortho-chlorinated 9f has lower thermal stability because of the steric clash with the bulky chlorine substituents (Figure 5). An interesting study shows how the Z-isomer thermal lifetime changes between two phenylazoindole

• substituted products 35e–g [51]. Examples Because of their red-shifted absorption and inverse stability, diazocines are suitable substitutes for azobenzenes in biological environments. Light with longer wavelengths can penetrate biological media, such as tissue, more effectively, and is less harmful to living

[3 + 2] Cycloaddition of thioformylium methylide with various arylidene-azolones in the synthesis of 7-thia-3-azaspiro[4.4]nonan-4-ones

• Daniil I. Rudik,
• Irina V. Tiushina,
• Anatoly I. Sokolov,
• Alexander Yu. Smirnov,
• Alexander R. Romanenko,
• Alexander A. Korlyukov,
• Andrey A. Mikhaylov and
• Mikhail S. Baranov

Beilstein J. Org. Chem. 2025, 21, 1791–1798, doi:10.3762/bjoc.21.141

• thermodynamically stable cis- and trans- isomers were also obtained in the reaction with azomethine ylides [20]. Finally, we performed preliminary derivatization studies of the obtained spiro-tetrahydrothiophenes. Compounds 7 and 9 demonstrated remarkable stability under both acidic and basic hydrolysis conditions

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

• , 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

• disintegration to avert reversibility. Given the benefits of the chemical stability of most aromatic macrocycles, creating stimulus-responsive complexes usually requires the guest components to undergo stimulus-triggered changes that affect their ability to bind with the host macrocycles. The controllable

• encapsulate DOX. This structure integrates multiple non-covalent interactions, such as hydrophobic interactions and π–π stacking, endowing the micelles with both structural stability and pH responsiveness. When targeted to the tumor microenvironment (acidic pH), the core of the micelles dissociates to achieve

Unique halogen–π association detected in single crystals of C–N atropisomeric N-(2-halophenyl)quinolin-2-one derivatives and the thione analogue

• Mai Uchibori,
• Nanami Murate,
• Kanako Shima,
• Tatsunori Sakagami,
• Ko Kanehisa,
• Gary James Richards,
• Akiko Hori and
• Osamu Kitagawa

Beilstein J. Org. Chem. 2025, 21, 1748–1756, doi:10.3762/bjoc.21.138

• ) observed in their single crystals. Results and Discussion Synthesis of quinoline-2-ones (thione), their enantiomer separation and rotational stability We focused on N-(2-halophenyl)quinolin-2-ones 1 and the thione analogue 2 as alternative substrates to verify chirality- and functional group-dependent

• poor (11% ee and 9% ee) [31]. In addition, rotational stability about the C–N bond in 1a,b was not mentioned at all. We prepared racemates rac-1a,b in accordance with Scheme 1 and separated their enantiomers [(P)-1a,b and (M)-1a,b] through medium pressure liquid chromatography (MPLC) using a semi

• be isolated because of the low rotational stability [32]. Quinolinone rac-1a was converted to quinoline-thione rac-2a by reaction with Lawesson’s reagent, and subsequently, the enantiomers [(P)-2a and (M)-2a] were separated by MPLC using a chiral IH column. Unfortunately, the barrier value of

Thermodynamics and polarity-driven properties of fluorinated cyclopropanes

• Matheus P. Freitas

Beilstein J. Org. Chem. 2025, 21, 1742–1747, doi:10.3762/bjoc.21.137

• cyclopropyl ring [9]. Building on these insights, the relative stability of all possible fluorinated cyclopropanes, from mono- to perfluorocyclopropane (Figure 1), was quantum chemically evaluated in this study. Polarity-dependent properties of the most polar compound were also analyzed to inform potential

• its ability to form ion complexes and self-assemble into a stacking arrangement [12][13][14]. Therefore, understanding the energetics and polarity of fluorinated cyclopropanes is crucial for elucidating the intramolecular forces that govern the stability of molecular structures. Moreover, these

• preclude its synthesis, as the all-cis-1,2,3-trifluorocyclopropane framework has been successfully prepared in earlier studies [17]. To better understand the intramolecular interactions that govern the stability of fluorinated cyclopropanes, the sets of di-, tri-, and tetrafluorinated cyclopropane isomers