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

• molecule which plays an important role in the biorefining industry. It was first isolated in 1832 by the German chemist Johann Wolfgang Döbereiner, and its structure was determined in 1901 by German chemist Carl Harries. In 1922, the Quaker Oats Company produced furfural on a large scale using oat hulls

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

• stereocenters, two of which are all-carbon quaternary stereocenters. Such a skeletally extraordinary structure poses significant challenges for total synthesis. In 2024, Stoltz and co-workers finished the divergent enantioselective total synthesis of (−)-hunterine A and (−)-aspidospermidine by utilizing a Ru

• sesquiterpenoids, toxicodenanes A–C and E (see representative structure 16 in Scheme 7) were isolated from Toxicodendron vernicifluum in 2013 to 2015 [63][64], whose structures feature the all-carbon bicyclic skeleton and four to seven contiguous stereocenters, posing significant challenges to their synthesis

• 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

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

• reported structures of alkaloids aspera chaetominines A and B have been synthesized. Moreover, the four-step synthesis of the reported structure of aspera chaetominine B generated another diastereomer that was converted in one-pot to (–)-isochaetominine C, which turned out to be the revised structure of

• , we have communicated the revision of the structure of versiquinazoline H to 11. During and after the latter work, we undertook further investigation on the last step of our approach to chaetominine-type alkaloids, namely, the lactamization reaction for synthesizing 3,14-cis-chaetominines and the DMDO

• (–)-isochaetominine A (4) and a diastereomer; 2) the diastereo- or enantiodivergent syntheses of chaetominine-family alkaloids and stereoisomers, and 3) the reported structures of aspera chaetominines A and B (12 and 13) and revised structure of aspera chaetominine B: 6 [(–)-isochaetominine C]. Results and Discussion

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

• biological evaluation of novel indolo[1,2-c]quinazoline derivatives, with a particular focus on their antiproliferative potential against human cancer cells. We introduced structural modifications at positions 5, 6, and 12 of the indolo[1,2-c]quinazoline core to explore the structure–activity relationships

• , offering valuable insights into their SAR and paving the way for a future evaluation of these compounds as anticancer therapeutics. Keywords: antiproliferative activity; antitumor agents; indolo[1,2-c]quinazoline; modification; structure–activity relationship; Introduction Organic compounds featuring

• for more extensive structure–activity relationship investigations. This work represents the first systematic evaluation of the anticancer potential of indolo[1,2-c]quinazoline derivatives, a chemotype previously studied mainly for synthetic accessibility but not for biological activity. Unlike prior

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

• , people began to be aware of the capability of mankind in making natural organic molecules. Since then, organic scientists are brave to challenge the complex organic structure of natural products given by nature [2][3][4][5]. To achieve the growing structural complexity of natural products, the synthetic

• against P-388 (mouse lymphocytic leukemia). Attracted by the novel bridged structure and in order to further determine the structure, particularly the absolute configurations, we explored the total synthesis of chabranol [19]. Structurally, this molecule contains an oxa-[2.2.1] bridge, with two quaternary

• the structure further, X-ray diffraction analysis of the derivative of bicycle 9 was obtained. This approach established the first total synthesis of chabranol in a concise way through the bioinspired Prins-triggered double cyclization strategy to rapidly construct the bicycle. Total syntheses of

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

• . Grossman et al. synthesized azobenzene-functionalized single-walled carbon nanotubes (SWCNTs) (Figure 3a) and demonstrated their application as solar thermal fuels [43]. The conformational restriction imposed by the chromophore-template structure combined with photochemically generated spatial strain

• light-harvesting carbazole units with photoresponsive azobenzene units in a unique macromolecular architecture (Figure 4c) [48]. The resulting cross-linked polycarbazole structure led to a high solar thermal storage capacity of 179.9 J/g and an extended half-life at 60 °C, increasing from 7 min for the

• Azobenzene small-molecule derivatives can be systematically categorized based on molecular structure into monoazobenzene derivatives [61][62][63][64][65][66][67][68][69], multiazobenzene derivatives [70][71][72][73], heteroaromatic azobenzene derivatives [74][75][76][77][78][79][80][81], and macrocyclic

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

• -1,2,4-triazoles, is important because the formation of different chemotypes of final heterocyclic compounds are possible depending on the structure of the reagents, the solvents and the catalysts, and type of activation methods [7][8][9]. MCRs of aminotriazoles, methylene-active compounds, and

• 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

• spectra probably indicates the formation of both possible diastereomers. The structure of compounds 6a–d was confirmed from the 1H NMR spectra and the mass spectra of mixture by comparison with literature data for similar pyrimidines [17][18]. Conclusion In summary, the multicomponent reaction of 3-amino

α-Ketoglutaric acid in Ugi reactions and Ugi/aza-Wittig tandem reactions

• Vladyslav O. Honcharov,
• Yana I. Sakhno,
• Olena H. Shvets,
• Vyacheslav E. Saraev,
• Svitlana V. Shishkina,
• Tetyana V. Shcherbakova and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2021–2029, doi:10.3762/bjoc.21.157

• ]. Therefore, these molecules can be considered as potential antidiabetic agents. α-Ketoglutaric acid (KGA) is an attractive precursor for medically oriented syntheses using multicomponent reactions due to its chemical structure as a dibasic keto acid and its role as an important component of numerous

• hours. The solvent was then evaporated, the residue dissolved in DCM, and stirred in the presence of Ph3P for 12 hours at 20 °C to give compounds 9c–e in 35–51% yields (Table 3). Identification and structure determination of the compounds obtained was based on elemental analysis, mass spectrometry, 1H

• shift of the signal in the 198 ppm region, corresponding to the carbonyl carbon of compounds 8, to a stronger field in quinoxalinones 9, where cyclization of the keto group has occurred. The structure of quinoxalinones of type 9 was finally assigned based on X-ray diffraction analysis made for 3-(4-(2

Understanding the origin of stereoselectivity in the photochemical denitrogenation of 2,3-diazabicyclo[2.2.1]heptene and its derivatives with non-adiabatic molecular dynamics

• Leticia A. Gomes and
• Steven A. Lopez

Beilstein J. Org. Chem. 2025, 21, 2007–2020, doi:10.3762/bjoc.21.156

• properties of 1, 3, and 5. We considered the molecular orbitals and electrons most critical for describing the electronic structure of the molecules in the reaction. The CASSCF [87]/ANO-S-VDZP [88] active space for 1 is shown in Figure 1; we considered 8 electrons and 9 orbitals, along with their average

• housane derivatives from 2,3-diazabicyclo[2.2.1]hept-2-enes. To determine the dominant mechanistic pathway, we started with a static exploration with the minimum steepest-descent energy path (MEP) from the FC-point along the S1 reaction coordinate. Figure 3 shows the MEP and the structure of S0, the last

• point of MEP, and S1 for 1, 3, and 5. These structures are important for understanding the geometrical changes after light absorption and determining the dominant mechanism pathway, along the S1-reaction coordinate. The MEP for 1 contains 17 geometries leading to the final structure 1-MEP-17, and the

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• aminopentynes 16a–c underwent allylic rearrangement, affording tetrahydropyridines 9 (Scheme 6). The tetrahydropyridine core was confirmed unambiguously by X-ray structure analysis of dinitrobenzamide 9c. More electron-rich acylamides reacted faster and gave less side-products, compared to more electron-poor

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

• intramolecular cyclization of 16 generated benzofuran 17 in 83% yield. After protecting the phenolic hydroxy group of 17, cross-metathesis (CM) with allylic alcohol 18 catalyzed by 13 furnished intermediate 19. Desilylation of 19 produced heliannuol G (20) and heliannuol H (21), with the structure of 21

• of the product in the same process by employing the antipodal ligand, as both enantiomers of the chiral ligand are normally accessible. Additionally, the substrate scope can be broadened by modifying the ligand’s structure. Early in 1984, Ichikawa and co-workers reported a Sn-mediated

• enhanced the reaction performance. However, excessively bulky substituents at C4 and substitutions at both C4 and C5 hindered the coordination between substrate and catalyst, and led to reduced enantioselectivity. As to the structure of 128, the electronic effect of the bromo-substituted pyridine moiety

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• products observed by analytical HPLC. Structures and structure elucidation of intermolecular reaction products. The relevant reactivity modes are indicated by colour: O–H insertion (green); N–H insertion (blue); formal C–H insertion (yellow); and cyclopropanation (pink). Synthesis of α-diazoamide

• substrates D1–5 of general structure 2 bearing S(VI) electrophiles. Panel A: Overview of synthesis (see Table 1 for details of synthesis of individual substrates). Panel B: Substrates that were prepared. Synthesis of α-diazoamide substrates of general structure 2 bearing S(VI) electrophiles (see Scheme 1

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

• characterized by NMR spectroscopy, mass spectrometry, and X-ray crystallography. Single crystals suitable for X-ray diffraction measurements of compounds 3a, MC2, and MC3 were successfully obtained to reveal their molecular structures. In the crystal structure of 3a (Figure 2a), the two pyrene units are nearly

• , theoretical calculations were performed to evaluate the energy barriers of isomerization. As shown in Figure S3 (Supporting Information File 1), the configuration observed in the crystal structure has the lower energy by 24.0 kcal mol−1 than that of the isomeric structure with two pyrene units at the same

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

• albumin was chosen as a model protein because of its well‐characterized structure and the presence of reactive sites that are known to be susceptible to alkylation. In standard aqueous media, the electrochemical oxidation of HSA can be observed via LSV as a broad wave, which is often attributed to the

• , tryptophan residues), as well as the overall structure of the protein. The peak intensity and shape can vary depending on pH, ionic strength, and protein conformation. However, under our conditions, the HSA oxidation was consistent, well‐defined, and served as a clear baseline reference. Subsequent to

• into the synthesis, cytotoxic behavior, and biochemical reactivity of glycidyl esters of phosphorus acids. The results support their potential as reactive anticancer candidates and lay a foundation for future structure–activity relationship studies and further development in medicinal chemistry

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

• purified through flash column chromatography on silica gel to give the isolated pure product. X-ray determined structure of chiral piperazine 2b. Synthesis of vicinal diamines via imino-pinacol coupling in the presence of metal-based reductants. Light-promoted imino-pinacol coupling for the synthesis of

• degli Studi di Milano) for provision of beamtime and Prof. Leonardo Lo Presti for structure solution and refinement are acknowledged. Funding The authors thank MUSA – Multilayered Urban Sustainability Action – project, funded by the European Union – NextGenerationEU, under the National Recovery and

Preparation of spirocyclic oxindoles by cyclisation of an oxime to a nitrone and dipolar cycloaddition

• Beth L. Ritchie,
• Alexandra Longcake and
• Iain Coldham

Beilstein J. Org. Chem. 2025, 21, 1890–1896, doi:10.3762/bjoc.21.146

• chromatography on silica gel. The structure of this isomer could not be ascertained with certainty from NOESY analysis and initial crystallisation attempts were unsuccessful. However, through use of encapsulated nanodroplet crystallisation (ENaCt), a high-throughput crystallisation technique which controls the

• , 52.7, 39.4, 26.8; HRESIMS (m/z): [M + H]+ calcd for C18H21N2O6, 361.1400, found: 361.1404. Representative oxindole alkaloids. Orientation for the cycloaddition (left) and the crystal structure of the major stereoisomer 5a (right) with the anisotropic displacement parameters drawn at 50% (oxygen – red

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

• synthesis of helically chiral, planarly chiral and inherently chiral molecules. General structure of CPAs and selected CPAs with various chiral scaffolds. Representative elements of molecular chirality. CPA-catalyzed asymmetric synthesis of azahelicenes via Fischer indole synthesis. CPA-catalyzed asymmetric

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

• , bottom), the thermal lifetimes drop significantly [38]. It is thus crucial to take into account the asymmetric nature of the imine bond and the steric hindrance of the substituents in the design of these photoswitches. For a detailed analysis of the structure–property relationship of these compounds we

• stator [95]. The photoswitching of arylhydrazones was first reported in 1976 by the group of Courtot [96][105], and the structure–property relationships were thoroughly studied by the Aprahamian group [108]. Electron-donating groups generally give a red-shifted spectrum, while electron-withdrawing groups

[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

• bioorganic chemistry [1]. Such substances are actively investigated in drug design, since their rigid 3D structure allows them to bind more selectively and effectively to biological targets in comparison to classical planar heterocycles [1][2][3][4][5]. Spirocyclic derivatives containing at least one five

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

• in pH, light, and enzyme activity, the binding affinity between the guest and host molecules can be altered, thereby achieving controlled drug release and targeted delivery. (2) Drugs are loaded into self-assembled host–guest systems [29][30][31][32]. The chemical structure or properties of the host

• processes. For example, supramolecular self-assembly technology enhances the targeting of chemotherapeutic drugs to tumor tissues, reducing systemic adverse reactions. (3) Macrocyclic aromatic supramolecular nano-valves have a pseudo-rotaxane structure with host–guest coordination and the kinetic properties

• of supramolecular interactions [33][34]. Different external stimuli, including pH changes, enzymes, light irradiation, hypoxia, and multi-stimuli responses, can alter the supramolecular structure or binding affinity to activate the opening and closing of the nano-valves. In addition to the three

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

• detected in the crystals of (P)-1a and (P)-1b. Angles (θ, α) and distances (d) in racemate rac-1a,b and (P)-1a,b. Crystal structure of racemic quinoline-2-thione rac-2a. Synthesis of N-(2-halophenyl)quinolin-2-ones 1a,b and quinoline-2-thione 2a. Supporting Information Crystallographic data for compounds

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

• advanced materials, particularly those whose properties rely on the polarity and spatial arrangement of C–F bonds within a cyclopropane framework. Keywords: cyclopropane; fluorination; polarity; theoretical calculations; Introduction Cyclopropane, the smallest cycloalkane, has a rigid structure that

• isomer among the 1,2,3,4,5,6-hexafluorocyclohexanes [10]. Although it was initially synthesized via a multistep reaction, it is now readily obtainable through the catalytic hydrogenation of hexafluorobenzene [11]. Its Janus-face-like structure has demonstrated unprecedented potential, particularly due to

• rely on specific properties such as dielectric anisotropy, where the molecular dipole moment aligns parallel to the molecule’s long axis [19]. Compound 1.2.3-c.c. exhibits a "Janus"-face-like structure, characterized by a positively charged region on one side and a negatively charged region on the

Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• function [16][17]. Malassezione (1, also referred to as malathidone [18]) is an AHR agonist [19][20]. Recently, in an effort to identify compounds as glucokinase activators to treat type 2 diabetes, structure-based virtual screening identified malassezione as a potential glucokinase activator [21

• fully consistent with those published previously [20]. The observation of 19 carbon atoms in 1 (HRESIMS) and 10 carbon signals in the 13C NMR spectrum is in accord with the molecule being symmetric. The structure of di-indole 1 was further supported by 2D NMR. The 1H-1H COSY spectrum showed couplings

3,3'-Linked BINOL macrocycles: optimized synthesis of crown ethers featuring one or two BINOL units

• Somayyeh Kheirjou,
• Jan Riebe,
• Maike Thiele,
• Christoph Wölper and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2025, 21, 1719–1729, doi:10.3762/bjoc.21.134

• ). The structure of Me-M16 was additionally verified by single-crystal X-ray analysis (the enantiomeric compound (R)-Me-M16 resulting from a separate synthesis was crystallized, see Figure 4). Due to the macrocyclic structure, the two ethylene glycol units directly attached to each dimethylphenyl linker

• formation of various by-products. Starting from the bistosylates Me/H/iPr-36, reaction with the diols Me/H/iPr-2 in the presence of Cs2CO3 as base (CH3CN, 80 °C) proceeded cleanly to give the desired hexaethylene glycol-linked bis-BINOL macrocycles that feature a 66-membered ring structure. Here, we

• bistosylates 85/6/7/8 (1.0 equiv), Cs2CO3 (2.0 equiv), CH3CN, 80 °C. Molecular structure of macrocycle (R)-Me-M16 in the solid state (hydrogen atoms are omitted for clarity and thermal ellipsoids are set at the 60% probability level). The ethylene glycol chain is partially disordered, only one component is

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

• monosaccharide components of an amino sugar-containing 1,1'-disaccharide require multiple orthogonal protecting or functional groups, the use of a picoloyl group at position 4 or 2 to stabilize the anomeric configuration is not feasible. In such cases, the structure of the lactol acceptor typically relies on 2N