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

• groups by sodium borohydride and then converted to chloromethyl groups by treatment with thionyl chloride, to give compound 2. The reaction of compound 2 with thiourea in THF gave compound 3 as a white solid in 96% yield. Compound 3 was characterized by 1H and 13C NMR in DMSO-d6 as a solvent (Figure 1

• ). The proton signals of the NH₂ and CH₂S groups of the isothiouronium substituents were clearly observed at 9.04 ppm and 4.23 ppm, respectively. Additionally, the carbon signal of the CH₂S group appeared at 169.3 ppm. The NMR signals, consistent with a fully symmetric structure, evidenced the exhaustive

• precipitate was recovered by filtration and washed several times with ethyl ether, to give pure compound 3 (118 mg, 96% yield). Characterization of compound 3: NMR spectra were acquired on a Bruker Avance 400TM spectrometer. Chemical shifts (δ, ppm) are reported referring to the residual peak of the solvent

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

• -connected ortho-bromobenzene subunit analogs failed under microwave irradiation but were successful using conventional thermal heating in yields of 31–65%. The expanded nature of the aromatic ring system following annulation was reflected by the downfield shifting of aromatic 1H NMR signals and the red

• shape differences by allowing such subunits to rotate out of coplanarity due to steric strain, diminishing conjugation between subunits. Formation of pentacyclic ring systems via annulation led to several expected spectroscopic signatures indicating the formation of an expanded aromatic π-system. 1H NMR

• the NMR timescale. These trends were observed similarly for the other analogs of this study (see Supporting Information File 1). Optoelectronic properties of each annulated product and its respective control compound were examined via UV–visible absorption and emission spectroscopy. Figure 6 shows the

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

• UV melting and ITC, Db2 showed especially poor affinity for the U–A base pair in HRP1. To help explain experimental binding results, we turned to computational molecular dynamics modeling using HRP1 and PNA1–3 as a model based on the PNA–dhRNA triplex provided by previous NMR studies [41] (for

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

• the compounds, while chloroform was used for cholesterol and lipid stock solutions. 1H NMR spectra were recorded using Bruker AV III 400 and Bruker AV III 500 spectrometers. 13C NMR was conducted on a Bruker AV III 500 spectrometer. All chemical shifts (δ) are reported in ppm, referencing residual non

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

• thiophene, promoting further study of these structures and reaction mechanism. 1H NMR spectroscopy of the obtained mixture provided the first key information about its nature, namely the presence of two major products 2 and 3, both of which showed three characteristic singlets with signal integration 1:3:3

• -nucleophiles to form sulfide 2 and disulfide 3. Optimization of the reaction conditions for the reduction–alkylation of disulfide 3. Supporting Information Supporting Information File 12: Full experimental details, characterization data, copies of NMR spectra and HRMS for all new compounds. Acknowledgements

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

• thoroughly characterized by 1H and 13C NMR spectroscopy, HRMS, and single-crystal X-ray diffraction analysis (Figure 1). A range of solvents was subsequently screened; however, none provided an improvement over 1,4-dioxane for this transformation (Table 1, entries 2 and 3). In addition to AgNO3, other silver

• of our method. Key mechanistic studies. Optimization studies.a Supporting Information Supporting Information File 9: Experiment details, characterization data, copy of NMR spectra of synthesized compounds, and single-crystal X-ray diffraction data. Supporting Information File 10: CIF file for 2a

Synthesis of the tetracyclic skeleton of Aspidosperma alkaloids via PET-initiated cationic radical-derived interrupted [2 + 2]/retro-Mannich reaction

• Ru-Dong Liu,
• Jian-Yu Long,
• Zhi-Lin Song,
• Zhen Yang and
• Zhong-Chao Zhang

Beilstein J. Org. Chem. 2025, 21, 2470–2478, doi:10.3762/bjoc.21.189

• along IRC path. e) Spin-density analyses of R-24 and F-10 (isovalue = 0.004). f) NBO analyses of the selected transient structures (isovalue = 0.04). Substrate scope. Conditions screening.a Supporting Information Supporting Information File 6: Experimental procedures, characterization data, NMR spectra

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

• determined by 1H NMR spectroscopy. (A) Conformers arising during the rotation around the C5–C6 bond in pyranosides. (B) Furanoside ring conformers of monosaccharide 2 in the pseudorotation diagram. The dashed colored circles denote the initial conformations taken for optimization. Solid colored circles

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

• transition state (Scheme 2). Meanwhile, the diastereomeric ratio of interest can be determined by integrating the 1H NMR spectra, in particular by selecting the appropriate signal pairs (one from each diastereomer) belonging to the respective cycloaddition product. An example of these selected protons (trans

• in Table 1, entry 9. As illustrated in Table 5, the product yields obtained from the reactions are presented alongside the observed cis/trans diastereoisomer ratios in the presence of the respective catalysts. However, upon examination of the 1H NMR spectra of compound 3a synthesized in the presence

• performed using silica gel (60 F254, Merck, Darmstadt, Germany) plates. Melting points were recorded using a Büchi melting point B-540 apparatus (Büchi Labortechnik AG in Flawil, Switzerland). The IR spectra were measured by Spectrum Two FT-IR spectrometer (PerkinElmer, Massachusetts, USA). The NMR spectra

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

• mmol scale experiment. The scope of the Fe-catalyzed spirocyclization. aIsolated yield of the 4.2 mmol scale experiment. The proposed mechanism of product 4 formation. Supporting Information Supporting Information File 2: General reaction procedures, compound characterization data, and copies of NMR

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• . Supporting Information Supporting Information File 34: Characterization data and 1H NMR, 13C NMR spectra of the compounds. Acknowledgements The authors sincerely acknowledge all of the anonymous reviewers for their valuable comments and suggestions. Funding We are grateful for financial support from the Qin

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

• rotationally restricted, all its accessible conformations constitute a subset of PBG's conformations. The binding constants and conformational change mechanisms of the two analogs were quantitatively evaluated by proton nuclear magnetic resonance spectroscopy (1H NMR), ultraviolet–visible absorption

• . Experimental PBG (CCDC Number: 2070280) and WDG were synthesized from phenyl- and fluorenyl-substituted precursors, respectively, via Friedel–Crafts alkylation (Scheme 1) according to our previous work [22]. Structural characterization was performed using 1H NMR (Figures S1 and S2) and mass spectrometry

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

• reported the first [3]rotaxane with three azobenzene units in the axle and two α-cyclodextrins as the macrocycle. The rotaxane was obtained as a single stereoisomer, where the two narrow rings of the cyclodextrin point to each other. Although no photoswitching studies were conducted, 1H NMR results showed

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

• but insoluble in CHCl3, CH2Cl2, methanol, acetone, acetonitrile, and hexane; G2W4: soluble in CHCl3, CH2Cl2, acetonitrile, DMSO, and TFA but insoluble in methanol, acetone, and hexane). The new hosts G2W1–G2W4 were fully characterized spectroscopically (1H and 13C NMR, IR, MS) and the data is in

• accord with the depicted C2v-symmetric structures. Figure 3 shows the 1H NMR spectra recorded for G2W1–G2W4 in DMSO-d6 at 400 MHz. As expected, all four hosts display two singlets for the equatorial CH3 groups (a, b), two pairs of doublets for the diastereotopic CH2 groups (c,c’ and d,d’) in the expected

• deshielding effect of the lone pairs on the adjacent OCH3 group and the neighboring aromatic ring. Similarly, the number of resonances in the 13C NMR recorded for G2W1 (19 observed, 19 expected), G2W2 (17 observed, 17 expected), G2W3 (13 observed, 13 expected), G2W4 (11 observed, 11 expected) are also

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

• fluorination attempts. Maintaining some residual solvent allowed for the characterization of compound 13 by NMR spectroscopy. Stereochemical assignment in 13 was based on a large trans-axial coupling constant JH2exo-H3 = 10.6 Hz in the 1H NMR spectrum and interactions between H3endo and H7endo on the

• oxymethylene bridge in the 2D NOESY NMR spectrum. Given the instability of fluoro-ketone 13, a one-pot procedure was developed in which the reaction mixture containing 13 was subjected to the Baeyer–Villiger oxidation with H2O2 giving the fluorinated and stable lactone 14, which is the expected kinetic product

Research towards selective inhibition of the CLK3 kinase

• Vinay Kumar Singh,
• Frédéric Justaud,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Blandine Baratte,
• Thomas Robert,
• Stéphane Bach,
• Chada Raji Reddy,
• Nicolas Levoin and
• René L. Grée

Beilstein J. Org. Chem. 2025, 21, 2250–2259, doi:10.3762/bjoc.21.172

• Supporting Information Supporting Information File 26: Detailed experimental procedures and spectral data, kinase inhibition studies, molecular modelling studies, analysis of dose-dependent effect of VS-77 on the kinase activity of Mm_CLKs and copies of the 1H and 13C NMR spectra. Acknowledgements We thank

A chiral LC–MS strategy for stereochemical assignment of natural products sharing a 3-methylpent-4-en-2-ol moiety in their terminal structures

• Rei Suo,
• Raku Irie,
• Hinako Nakayama,
• Yuta Ishimaru,
• Yuya Akama,
• Masato Oikawa and
• Shiro Itoi

Beilstein J. Org. Chem. 2025, 21, 2243–2249, doi:10.3762/bjoc.21.171

• A terminal 3-methylpent-4-en-2-ol (MPO) moiety is a common structural feature in various polyketide natural products. Stereochemical assignments of this moiety have mainly relied on computational analyses of NMR, ECD, and specific rotation data. However, none of these approaches can be applied to

• research areas, including the development of synthetic methodologies, the investigation of modes of action, and the evaluation of pharmacological potential, among others. Advancements in spectroscopic techniques, such as nuclear magnetic resonance (NMR) and mass spectrometry (MS), have enabled the

• typically determined using NMR-based techniques, such as coupling constant analysis and NOE experiments, sometimes with the aid of computational chemistry [3][4][5][6][7]. In contrast, absolute configuration remains more challenging to determine, as it frequently requires chemical degradation or

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

• from phenylhydrazine and aryl bromides. The gray box provides a detailed list of all identified side-products. Supporting Information Supporting Information File 20: Details of optimization experiments, full characterization data, and NMR spectra (1H, 13C, 19F) for all products. Funding L.G

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

• variety of new tri-, tetra- and pentacyclic ring systems. The structural characterization of (E)- and (Z)-hydrazones was supported by 2D NMR techniques, while that of the target compounds by single-crystal X-ray measurements. The hydrazone intermediates and the new title compounds were subjected to a

• spatial proximities obtained from either NOESY or ROESY NMR measurements. The NH moiety is close to N=CH in the (E) isomer, while NH is close to CH2 in the (Z) isomer. As an example, in case of hydrazone 7h, a selective 1D NOESY spectrum was recorded with the excitation of NH (Figure 2 and Figure 3). In

• both Figures, beside the selective 1D NOESY spectrum (upper part in Figure 2 and Figure 3), the 1H NMR spectrum (lower part) is also presented. The spatial proximity of NH with N=CH (marked with a red arrow in Figure 2) or with CH2 (red arrow in Figure 3) proves the (E) or (Z) configuration of the N=C

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

• , empirical approaches based on 1H NMR anisotropy method have gained attention as alternative strategies for stereochemical assignment of chiral molecules. Among these, the modified Mosher method, which utilizes the ring current effects of aryl substituents, has been extensively applied to chiral alcohols [2

• used without further purification. Melting points were obtained with a Mel-Temp capillary apparatus and were not corrected. IR spectra were obtained as KBr disks on a JASCO FT/IR-410 spectrophotometer. The FAB mass spectra were recorded using a JEOL 600H mass spectrometer. 1H and 13C{1H} NMR spectra

• were recorded on a Jeol ECP400 spectrometer (400 MHz) and a Bruker AVANCE II spectrometer (400 MHz). All NMR spectroscopic data of CDCl3 solutions are reported in ppm (δ) downfield from TMS. UV and CD spectra were recorded on JASCO V-650 and JASCO J-820 spectrometers, respectively. X-ray single-crystal

Synthesis of triazolo- and tetrazolo-fused 1,4-benzodiazepines via one-pot Ugi–azide and Cu-free click reactions

• Xiaoming Ma,
• Zijie Gao,
• Jiawei Niu,
• Wentao Shao,
• Shenghu Yan,
• Sai Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 2202–2210, doi:10.3762/bjoc.21.167

• 1H NMR spectra are different (Figure 2). The most evident differences are the disappearance of the signal for the alkyne H at 2.36 ppm in the spectrum of 6a and the appearance of a peak at 8.14 ppm for the proton on the triazole ring of 8a. The aromatic protons in 8a show two distinct doublets and

• 7a–k in 36–90% yields, 8a–g in 77–92% yields. Note: When 2-yn-1-amine hydrochlorides 2b–e were employed in this one-pot reaction, Et3N (0.3 mol, 1.5 equiv) was added into the vessel at the initial stage. Some bioactive molecules bearing triazole, tetrazole, and 1,4-benzodiazepin rings. 1H NMR spectra

Further elaboration of the stereodivergent approach to chaetominine-type alkaloids: synthesis of the reported structures of aspera chaetominines A and B and revised structure of aspera chaetominine B

• Jin-Fang Lü,
• Jiang-Feng Wu,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2025, 21, 2072–2081, doi:10.3762/bjoc.21.162

• intermediate 17 [65] yielded the thermodynamically stable C2/C11-trans and C3/C14-trans diastereomers 19 and 20 (dr = ca. 1:1) in a combined yield of 75% (Scheme 2). The 1H NMR spectrum of this diastereomeric mixture shows only one set of resonance signals, but two sets of resonance signals were observed on

• the 13C NMR spectrum. We have succeeded in preparing a single crystal from the oxidation products. Interestingly, the X-ray diffraction analysis [66] showed that the single crystal contained two diastereomers (19/20) with the structures displayed in Scheme 2. Similarly, the DMDO oxidation of

• cytopathogenicity in MDCK cells with IC50 values of 15.5 and 24.5 μM, respectively. Attracted by both their structure and bioactivities, we anticipated their synthesis. The author determined the structure by means of spectroscopic (1H, 13C NMR, HSQC, HMBC, and 1H-1H COSY), and MS analysis, and claimed that “their

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

• a series of 6-aminomethyl-substituted indoloquinazoline derivatives 14а–d (Scheme 5). The structures of all compounds were analyzed and confirmed by NMR and HRMS methods. Samples of all indolo[1,2-c]quinazoline derivatives with good analytical purity (HPLC, ≥95%) were further subjected to biological

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

• products capillosanol and chabranol, respectively [18]. Chabranol was identified to contain a new bridged skeleton through extensive NMR experiments. However, no single-crystal X-ray diffraction analysis was conducted, making the structural determinations not that solid. It showed moderate cytotoxicity

• subsp. brachystachys, and discovered a series of complex natural products named sargalmides A–E [43] (Scheme 7a). To clearly elucidate the complex structures, Yue and co-workers used multiple methods including extensive spectroscopic analysis (NMR, IR and MS), X-ray crystallography, quantum-chemical

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

• characterized by the following signals in the 1H NMR spectra: a proton singlet of the pyrimidine NH group at 8.30–8.31 ppm, a multiplet of aromatic protons in the region of 6.95–7.51 ppm, a proton multiplet of the CH group at 4.65–4.68 ppm and singlet for protons for the triazole CH3O group at 3.7 ppm. The 1H

• NMR spectra of heterocyclic acids 5a–c exhibited a broad singlet of proton of the carboxyl group at 11.88–14.02 ppm, a singlet of proton of the hydroxy group at 9.41–9.86 ppm, a singlet of proton of the pyrimidine NH group at 7.72–7.91 ppm, a singlet of proton of the triazolylamine NH group at 7.44