Chemoenzymatic synthesis of the cardenolide rhodexin A and its aglycone sarmentogenin

• Fuzhen Song,
• Mengmeng Zheng,
• Dongkai Wang,
• Xudong Qu and
• Qianghui Zhou

Beilstein J. Org. Chem. 2025, 21, 2637–2644, doi:10.3762/bjoc.21.204

• Fuzhen Song Mengmeng Zheng Dongkai Wang Xudong Qu Qianghui Zhou Engineering Research Center of Organosilicon Compounds & Materials (Ministry of Education), Hubei Key Lab on Organic and Polymeric OptoElectronic Materials, College of Chemistry and Molecular Sciences, The Institute for Advanced

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

• (intramolecular charge transfer) process. Keywords: fluorescence; hybridization; imidazo[1,2-a]pyridines; Knoevenagel reaction; thiazolidinone; Introduction Heterocycles are compounds of significant interest to organic chemists as drug candidates due to their already widespread presence in many commercially

• ], diammonium phosphate (DAP) [43], and tetrabutylammonium bromide (TBAB) [44]. Organic bases like morpholine [45], triethylamine [46], ethanolamine, and piperidine [47] and heterogeneous catalysts from Cu [48], Ti [49], and Zn [50] metal compounds have also been used. Common solvents are ethanol [51], toluene

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

• -sized” molecular box has been used to extract various anions from water [12]. Another family of macrocyclic compounds suitable for anion recognition and binding are bambusurils (BUs). BUs act as very potent anion receptors in both organic solvents and water. Furthermore, their portals can be variously

• in organic solvents. Results and Discussion Decoration of silica gel with bambusuril For the modification of silica gel (SG), we selected previously reported bambus[6]uril BU1 (Scheme 1) containing 12 carboxyalkyl substituents [13]. This macrocycle was chosen for several reasons: BU1 can be attached

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

• Vasudevan Dhayalan Department of Chemistry, National Institute of Technology Puducherry, Karaikal-609609, Puducherry, India 10.3762/bjoc.21.200 Abstract Over the past two decades, organocatalyzed visible-light-mediated radical chemistry has significantly influenced modern synthetic organic

• -coupling processes. This cooperative organic dual catalysis has great potential in medicinal, pharmaceutical, and materials science applications, including the development of organic semiconductors and polymers. In recent years, NHC-involved photocatalysis has attracted considerable attention in synthetic

• organic chemistry, and particularly in the late-stage functionalization of bioactive compounds, drugs, and natural products. This review highlights recent advances in NHC–organophotoredox dual catalysis, focusing on methodology development, mechanistic insights, and reaction scope for synthesizing

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

• primary driving forces behind the advancement of organic synthetic chemistry. With rapidly evolving organic synthesis technologies, a diverse array of novel methods and sophisticated strategies continues to emerge. These approaches not only complement and synergize with one another but also significantly

• diterpenoids; synthetic strategy; total synthesis; Introduction Organic synthesis, as a cornerstone of chemical research, is dedicated to constructing complex natural products or target molecules from simple and readily available starting materials via a series of precise and efficient chemical reactions

• ) exhibits high specificity and regulatory effects on ryanodine receptors (RyRs) [19][20]. It is among the few small organic molecules identified to date that can modulate these receptors. Dysfunctions of RyRs are closely associated with various diseases: mutations in RyRs can cause genetic disorders such as

Rapid access to the core of malayamycin A by intramolecular dipolar cycloaddition

• Yilin Liu,
• Yuchen Yang,
• Chen Yang,
• Sha-Hua Huang,
• Jian Jin and
• Ran Hong

Beilstein J. Org. Chem. 2025, 21, 2542–2547, doi:10.3762/bjoc.21.196

• Yilin Liu Yuchen Yang Chen Yang Sha-Hua Huang Jian Jin Ran Hong Faculty of Chemical Engineering and Energy Technology, Shanghai Institute of Technology, 100 Haiquan Road, Shanghai 201418, P.R. China State Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy

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

• Department of Chemistry, Ohio Wesleyan University, Delaware, OH, 43015, USA Department of Chemistry, Binghamton University, 4400 Vestal Parkway East, Binghamton, NY 13902, USA Latvian Institute of Organic Synthesis, Aizkraukles 21, Riga, LV-1006, Latvia 10.3762/bjoc.21.193 Abstract Non-coding ribonucleic

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

• Roman A. Irgashev Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, Ekaterinburg, 620137, Russia 10.3762/bjoc.21.191 Abstract A versatile synthetic route to thieno[3,2-b]thiophenes was elaborated from dimethyl 3-nitrothiophene-2,5-dicarboxylate

• functionalized thieno[3,2-b]thiophenes with potential applications in pharmaceutical and materials chemistry. Keywords: aromatic nucleophilic substitution; disulfide derivative; 3-nitrothiophene; organic disulfides; thieno[3,2-b]thiophene; thiophene ring closure; Introduction Thieno[3,2-b]thiophene (TT

• ) derivatives are a valuable class of fused heteroaromatic compounds characterized by rigid planar π-conjugated backbones that provide narrow band gaps, high charge carrier mobility, and intermolecular π–π stacking interactions, making them particularly attractive for the design of organic materials. Indeed

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

• are ubiquitous and privileged heterocyclic scaffolds in various functional organic materials and naturally occurring products. Although extensive efforts have focused on developing synthetic strategies toward carbazole derivatives, direct regioselective functionalization of the carbazole core remains

• valuable platform for the selective functionalization of carbazoles, offering potential applications in optoelectronics, functional organic materials, and related areas while contributing to the advancement of C–H activation methodologies. Keywords: C–H activation; carbazole; catalysis; nitration

• strategies in streamlining access to nitro-functionalized carbazoles for applications in organic synthesis and materials science. Experimental A 15 mL pressure tube was charged with Pd2(dba)3 (18.3 mg, 0.02 mmol, 10 mol %), N-(pyridin-2-yl)-9H-carbazole 1 (0.2 mmol, 1.0 equiv), and AgNO3 (41 mg, 0.24 mmol

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

• donor; haloacetimidates; haloacetonitrile; two-chamber reactor; Introduction Trifluoroacetonitrile is an electrophilic reagent that has seen a variety of uses, mostly for incorporating trifluoromethyl groups into organic compounds [1]. As an example it has been successfully utilized for the synthesis

• danger of working with this toxic gas, restricts its use in laboratory scale synthesis. Consequently, when used in organic synthesis, trifluoroacetonitrile is typically synthesized on demand. The most common method is by dehydration of trifluoroacetamide using Gilman’s method with phosphorous pentoxide

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

• Alexey G. Gerbst Sofya P. Nikogosova Darya A. Rastrepaeva Dmitry A. Argunov Vadim B. Krylov Nikolay E. Nifantiev Laboratory of Glycoconjugate Chemistry, N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, 119991 Moscow, Russian Federation 10.3762/bjoc

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

• many applications in industry, but also plays an important role in many fields, such as electronics [3], agriculture [4], environmental protection [5] and cosmetics [6]. Chiral organic selenium-containing compounds also have important applications in organic synthesis and biomedicine [7][8]. These

• compounds can participate in asymmetric synthesis reactions and construct chiral molecules with specific stereoconfiguration, which is particularly critical for drug synthesis [9]. In the field of organic catalysis, chiral organic selenium-containing compounds can be used as chiral ligands or catalysts to

• participate in various types of asymmetric reactions, significantly improving the selectivity of reactions (Figure 1) [10][11][12][13][14]. Catalytic asymmetric synthesis is the main method to construct chiral organic selenium-containing compounds. Centrally chiral selenium-containing compounds can be

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

• -dihydronaphthalenes. Silva et al. have also developed an effective method for the stereoselective oxidation of tetralone derivatives using chiral hypervalent iodine reagents [61][62]. Hypervalent iodine compounds are widely used in organic synthesis as selective oxidants and enantiomerically pure reagents. In terms

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

• against other solvents. Keywords: cycloaddition; fused isoxazolidines; renewable solvent; reusable solvent; trans-diastereoselectivity; Introduction It is an established fact that a significant number of conventional organic solvents, which are widely utilized in both industrial and academic contexts

• different sources [4][5]. In order to fulfil this requirement, a considerable number of green solvents of various classes have been developed for a range of applications, including the extraction of natural compounds [6][7][8][9], food analysis [10][11][12], pharmacology [13][14][15], and organic synthesis

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

• -unsaturated ketone; dearomatization; indole; spirocyclization; spiro[indoline-3,2'-pyrrolidine]; Introduction Spiro[indoline-3,2'-pyrrolidine] derivatives represent an important class of organic compounds found in both natural products (e.g., coerulescine [1], horsfiline [2], and elacomine [3]) and synthetic

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

• supported by the National Natural Science Foundation of China (No. 62074081), the Project of State Key Laboratory of Flexible Electronics, Nanjing University of Posts and Telecommunications (No. ZS030ZR24020), the Synergetic Innovation Centre for Organic Electronics and Information Displays and the Priority

Adaptive experimentation and optimization in organic chemistry

• Artur M. Schweidtmann and
• Philippe Schwaller

Beilstein J. Org. Chem. 2025, 21, 2367–2368, doi:10.3762/bjoc.21.180

• de Lausanne (EPFL), Lausanne, Switzerland National Centre of Competence in Research (NCCR) Catalysis, École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland 10.3762/bjoc.21.180 The field of organic chemistry is undergoing a remarkable transformation. The convergence of laboratory

• automation and artificial intelligence is creating unprecedented opportunities for accelerating chemical discovery and optimization [1][2]. This thematic issue explores how adaptive experimentation, automation, and human–AI synergy are reshaping organic chemistry research. Several key technological advances

• this field and the exciting opportunities ahead. As methods for adaptive experimentation continue to advance, maintaining focus on effective human–AI collaboration will be crucial for realizing the full potential of these technologies in organic chemistry. This integration of automation, machine

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

• stiff-stilbene facilitated the formation of aggregates, resulting in organic room-temperature phosphorescence. The phosphorescent properties can be modulated by inducing macrocycle translation through acid–base stimuli or by disrupting the aggregates via stiff-stilbene photoisomerization. The authors

• . 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

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

• due to its simplicity, efficiency, low cost, and the absence of hazardous byproducts [6]. Many different adsorptive materials have been investigated including activated carbon [7][8][9], hybrid nanomaterials [10], metal oxide-based hybrid materials [11], metal organic frameworks [12], polymers [13

• that β-cyclodextrin (Figure 1)-based polymers could remove organic micropollutants from water [15][16]. For example, in 2021, Sessler and co-workers reported the synthesis of a calix[4]pyrrole (Figure 1)-based porous organic polymer, which exhibits the rapid uptake of dyes from water [17]. In addition

• -type receptors (e.g., H2) and studied their use as sequestrants for organic micropollutants [39]. In this paper, we extend this line of inquiry toward the use of the water-insoluble glycoluril dimer-derived acyclic CB[n] as sequestrants for dyes. Results and Discussion This Results and Discussion

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

• transformations is also discussed. Keywords: chiral Lewis acid; electrochemistry; enantioselective radical reaction; organocatalysis; photoenzymatic catalysis; photoredox; Introduction Asymmetric catalysis plays an integral role in the enantioselective synthesis of organic compounds. A wide variety of

• enantioenriched catalysts ranging from chiral organometallic complexes to organocatalysts (small organic molecules) have been designed, synthesized, and successfully used in several organic transformations [1][2][3]. Despite these advances, catalytic methods involving radical intermediates were very rare until

• include the use of transition metals or photoredox catalysts. In photoredox catalysis, radical generation often involves single-electron transfer (SET) to or from a photoexcited state of a photoredox catalyst, usually a metal complex or organic molecule. Two other notable strategies for radical generation

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

• rapid molecular diversification, offering transformative potential for green chemistry and pharmaceutical applications. By unifying mechanistic insights with practical synthetic design, this review provides valuable guidance for future innovations in precision organic synthesis. Keywords: economical

• synthesis; 1,n-enynes; pathway economy; small-molecule skeletons; Introduction As organic synthesis concepts continue to evolve, economical synthesis remains a foundational principle for synthetic chemists [1][2][3][4][5][6][7]. The essence of economical synthesis lies in the conservation of materials and

• importance of reducing the time required for reaction processes and conducting multistep reactions within a single pot (Scheme 1a) [6][7]. Contemporary organic synthesis is progressively approaching ideal synthesis – achieving highly functionalized target molecular frameworks in a single step. This paradigm

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

• off and washed with EtOAc (3 × 5 mL). The organic phase was washed with water (5 mL) and brine (5 mL), dried over MgSO4 and evaporated to give crude products 3, which were purified by flash chromatography. 2,4-Dimethyl-2,7,8,9,10,11-hexahydro[1,2,3]thiadiazino[6,5-a]carbazole 1,1-dioxide (3e

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

• Lifen Peng Ting Wang Zhiwen Yuan Bin Li Zilong Tang Xirong Liu Hui Li Guofang Jiang Chunling Zeng Henry N. C. Wong Xiao-Shui Peng Key Laboratory of Theoretical Organic Chemistry and Functional Molecule of Ministry of Education, School of Chemistry and Chemical Engineering, Hunan University of

• of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, P. R. China 10.3762/bjoc.21.166 Abstract Organic five-membered rings have shown significant applications in the fields of organic synthesis, natural products, organic materials and pharmaceuticals for their unique

• reaction mechanisms are disclosed if available. Keywords: alkyne; catalysis; cyclization; electrochemistry; five-membered ring; Introduction Organic five-membered rings, an essential class of organic compounds, not only are frequently used as important starting materials, intermediates or ligands in

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 Science and Technology, 1037 Luoyu road, Wuhan 430074, China 10.3762/bjoc.21.165 Abstract The carbonyl group is central in organic synthesis, thanks to its ability to undergo a vast range of different chemical transformations on its carbon center or at the neighboring positions. Due to the high

• organic synthesis. Therefore, synthetic chemists can base strategies on the existing reactivity of carbonyl compounds for defining novel routes converting biobased platform molecules containing carbonyl groups to prepare fine organic chemicals [21][22]. Following this approach, researchers can obtain

• evolves towards cyclic acetals (Scheme 4) [32]. Exploring methods for the conversion of glycolaldehyde (GCA) to 3-(indol-3-yl)-2,3-dihydrofurans in organic solvents, Gu et al. reported a three-component reaction combining GCA, ethyl acetoacetate as 1,3-dicarbonyl component and indole. Using glycolaldehyde

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

• dicarbonyl substrates, as well as their applications in the synthesis of various complex natural products will become a focal point in the field of organic synthetic chemistry. Several representative terpenoid and alkaloid natural products synthesized by applying desymmetric enantioselective reduction