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

• [52], acetic acid [53], or solvent-free processes [54]. Ionic liquids, such as [Bu4N][OH] [55], [bmim][OH] [56], and [Et3NH][HSO4] [57], and deep eutectic solvents (DES) [58] have been introduced to improve efficiency. Traditional methods for synthesizing these compounds, however, face several

• inconsistency made it challenging to rely on NMR as the primary method for confirming the structure of the expected products. To overcome this limitation, other analytical techniques, such as mass spectrometry and infrared (IR) spectroscopy, were employed. These methods successfully corroborated the formation

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

• ][2][3][4][5][6]. Recently developed photocatalysis affords sustainable, regioselective green methods for producing a wide range of functionalized carbonyl compounds and their related bioactive chiral intermediates under mild conditions, employing dual organic photoredox catalysis [7][8][9][10][11

• continued integration of this versatile photocatalytic platform with sustainable methods such as visible-light harvesting and the use of earth-abundant catalysts is expected to further enhance its impact across diverse research fields, including chemical biology, pharmaceuticals, agrochemicals, polymers

• cross-coupling between the C-centered and N-centered radicals. These methods are expected to open new avenues for visible-light- and NHC/4CzIPN-catalyzed carbon–heteroatom bond-forming processes (Scheme 1) [51]. In 2021, Studer et al. developed a novel method for the 1,3-difunctionalization of

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

• Zhi-Qi Cao Jin-Bao Qiao Yu-Ming Zhao Key Laboratory of Applied Surface and Colloid Chemistry of MOE & School of Chemistry and Chemical Engineering, Shaanxi Normal University, Xi’an, 710119, China 10.3762/bjoc.21.198 Abstract Innovations in synthetic methods and strategic design serve as the

• 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

• focuses on reviewing the efficient application of ring-construction methods and synthetic strategies in the total synthesis of highly oxidized Ryania diterpenoid natural products, emphasizing the pivotal role of novel synthetic methods and strategic innovations. Keywords: natural products; Ryania

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

• promising candidates for further investigations as a drug delivery system. The entrapment of different drugs combined with the intrinsic anticancer activity of the nanoassemblies could provide new agents for a combination multidrug anticancer treatment. Experimental Materials and methods: All chemicals were

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

• Supporting Information Supporting Information File 4: Description of materials, experimental methods, synthetic procedures, analytical characterization and copies of NMR spectra for novel compounds. Funding Research reported in this publication was supported by the National Institute of General Medical

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

• perform equally well using conventional heating methods. Aniline 10 and carboxylic acid 13 were combined under standard (HBTU) amide coupling conditions to afford benzyl ester 14 in 52% yield. Compound 14 was subsequently debenzylated via hydrogenolysis to afford the target Db2 monomer 15 in 77% yield

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

• and functional materials (Scheme 1a) [62][63][64][65][66]. Traditional electrophilic aromatic substitution methods for the nitration of carbazole typically result in a mixture of 1-nitro-, 2-nitro-, and 3-nitro-substituted isomers (Scheme 1b) [67]. Therefore, developing a method for the regioselective

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

• formation of unique radical intermediates [9][10]. We previously demonstrated the Ir-catalyzed [2 + 2] cyclization/retro-Mannich reaction of a tryptamine-substituted cyclopentenone F, which led to the formation of indoline J (Figure 1b) [15]. Unlike other reported methods [16][17][18], the PET reaction of F

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

• [10] (Figure 1), Swern conditions [11][12], PPh3 and CCl4 under basic conditions or by using trifluoroacetic anhydride in pyridine [13]. Other methods involving HF or small fluorinated gaseous compounds at high temperatures have been developed, but are not practical in a standard research laboratory

• synthesis of several glycosyl haloacetimidates and benzyl fluoroacetimidates, with different substituent patterns. The method allows for a larger substrate scope of halonitriles than earlier methods and is easily facilitated by low cost commercially available equipment. Examples of methods for the synthesis

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

• ] and vaccines [15][16][17][18]. That is why new efficient and stereoselective methods for the synthesis of both Galf-containing mono- and oligosaccharide derivatives are highly demanded. It is a well-known fact that galactofuranose form constitutes only 5% in water solution of unprotected ᴅ-galactose

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

• catalytic asymmetric synthesis methods. Only recently, methods for the formation of C–Se bonds have been established for the construction of selenium-containing atropisomers. However, there is no comprehensive review to summarize this great progress. In this paper, the catalytic asymmetric synthesis 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

• contraction of six-membered cycles in the synthesis of functionalized cyclopentane/enones, which are biologically active compounds. The main synthetic methods of ring contraction (ozonolysis–aldol condensation, ozonolysis–Dieckmann reaction, Baeyer–Villiger cleavage–Dieckmann reaction) and rearrangements

• compound was synthesized from the Diels–Alder adduct 14 between LG and 1,3-butadiene by two methods – vicinal hydroxylation of the double bond followed by periodate cleavage of the vic-diols and ozonolysis of the double bond. Alternatively, Wagner oxidation of the double bond in adduct 14 by treatment with

• , particularly iridoids. One of the promising methods for ring contraction in the absence of multiple bonds in the six-membered ring of terpenoids was proposed by Grishko et al. [26] (Scheme 6). The key step of 2,3-fragmentation was the cleavage of an enolized C–C bond at a keto group, followed by an

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

• scaffolds. From the standpoint of organic chemistry, it is evident that these compounds can be efficiently converted into a variety of versatile organic intermediates through the application of ring-opening reactions [49][50][51][52]. In addition to the aforementioned useful properties, the current methods

• solvent polarity results in a decrease in rate constants. This phenomenon is attributed to the lower polarity of the transition state in comparison to that of the initial compounds [61]. Furthermore, these methods often require harsh reaction conditions, prolonged reaction times, and laborious

• overlooked [69]. However, these methods are accompanied by the inevitability of long reaction times or the use of toxic organic solvents. Such negative aspects encountered during the synthesis of these compounds prompted us to seek alternative, environmentally benign, renewable, and reusable solvents [70

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

• e) [12]. The second category of synthetic methods relies on more accessible, non-pre-functionalized starting materials and stepwise assembly of the spirocyclic core. This strategy enables the synthesis of functionalized 3H-indoles, which can be further elaborated into structurally diverse products

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

• the deep understanding of experienced chemists. Looking ahead, several key challenges and opportunities are apparent. Integrating prior knowledge and transfer learning between chemical domains remains difficult but promising. Improved methods for uncertainty quantification could help identify when

• 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

Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• ’ linkage. Boc removal then completed their total synthesis of complanadine B [28]. Notably, while complanadine B could be derived from complanadine A via a selective enzymatic oxidation, attempts to achieve this transformation using chemical methods were unsuccessful. For instance, treatment of 36 with

• catalysis, C–H activation methods, biomimetic synthesis, classic rearrangements, skeletal editing logic, and others. In addition, these efforts enabled the identification of the potential cellular target of complanadine A, validation of its neurotrophic activity, establishment of preliminary structure

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• to construct a β-lactam, an α-metallated piperidine equivalent, overcoming poor yields and stereoselectivity in traditional methods. Its palladium-catalyzed cross-coupling with 2-bromolycodine via β-lactam C–C cleavage enabled stereoretentive coupling, efficiently synthesizing lycoplatyrine A and its

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

• [5][6]. Methylene blue is a particular concern given its widespread use in the textile, paint, and food industries as well as its pharmaceutical use as a treatment for methemoglobinemia and cyanide poisoning [4]. The improvement of known and development of new methods to remove dyes from water bodies

• crystal structures by X-ray diffraction methods. Figure 5a shows a cross-eyed stereoview of one molecule of G2W3 in the crystal. Crystals of G2W3 are monoclinic with the P21/c space group (a/Å = 10.0768(9); b/Å = 13.4198(11); c/Å = 32.411(3); α/° = 90, β/° = 98.135(3), γ/° = 90). As has been observed

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

• influenza [7], while chlorinated analogues such as 3 have demonstrated activity against hepatitis C (Figure 1) [8]. Stereoselective methods to access halogenated γ-butyrolactones are therefore valuable, as they enable access to nucleoside analogues which have applications in treating cancer and certain

• traces of the desired product. Methods for the installation of a CF3-group on enones are limited, although approaches have been applied to quinones, uracils, flavones or arylenones via radical pathways [39][40][41][42]. As per the fluorination reactions, we envisaged that a leaving group in the β

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

• 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

• catalysis is discussed initially. This is followed by the recently emerging areas of transition-metal catalysis, photoenzymatic catalysis, and electrochemistry. Perspective Radical generation and reactions Synthetic methods based on free radical chemistry are some of the most efficient and powerful tools

• has been largely supplanted by greener methods employing less-toxic reagents. Using alternative methods, radicals can be generated by hydrogen atom transfer (HAT), resulting in the homolytic cleavage of a carbon–hydrogen bond. Other approaches for radical generation in modern radical transformations

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

• substrate class. Through mechanistic-guided modulation of catalysts, solvents, ligands, and angle strain, this approach achieves unprecedented reaction pathway control while demonstrating superior temporal and step efficiency compared to conventional methods. The work establishes a sustainable framework for

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

• derivatization. Several derivatization methods using chiral anisotropic reagents, including α-methoxy-α-trifluoromethylphenylacetic acid (MTPA), phenylglycine methyl ester (PGME), and Marfey’s reagents, are widely used [8][9][10], although their applicability is restricted by the presence of specific functional

• analysis, and computational methods have been widely used. For example, the absolute configuration of chaetomugilin B [19] was determined by X-ray crystallography, while that of capsulactone (1) was established through density functional theory (DFT)-based simulations of NMR chemical shifts and electronic

• methods. We had also independently re-isolated compound 1 (1.2 mg) from the fungus Fusarium sp. (see Supporting Information File 1) and subsequently subjected 100 μg of 1 to the sequential degradation steps; (1) p-nitrobenzoylation of the two hydroxy groups, (2) RuO4 oxidation to cleave olefins including

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

• Paris, France 10.3762/bjoc.21.170 Abstract Azobenzenes are photoresponsive compounds widely used in molecular switches, light-controlled materials, and sensors, but despite extensive studies on symmetric derivatives, efficient methods for synthesizing non-symmetric analogues remain scarce due to

• , most synthetic methods have focused on the preparation of symmetric derivatives [12][13]. Traditional approaches, such as oxidative coupling of anilines [14][15][16][17][18][19], reductive coupling of nitroarenes [20][21][22][23], or cross-coupling between anilines and nitroarenes have proven

• efficacious but face significant challenges when applied to non-symmetric systems [24], particularly in achieving regioselectivity. These methods frequently require a particular reagent pair or an excess of one reactant, which limits their efficiency and versatility. In contrast, Baeyer–Mills reactions, which

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

• ). Analytical methods. All samples of the kinetic solubility and in vitro permeability assays were analyzed on a Waters Alliance 2695 Separations Module equipped with a 2996 PDA detector, using a Water Xterra RP 18 chromatographic column (100 × 4.6 mm, 3.5 µm) at 45 °C, applying 1.2 mL/min flow rate. For a 7

• C17H18N4O2S, 342.1156; found, 342.1151. General methods for the synthesis of compounds 3a–j and 10a,b. Method A, step 2 [26][27]: A suspension of the corresponding crude hydrazone 7 or 9 (100 mg) and p-TsOH monohydrate (1.80 equiv) in toluene (1 mL) was refluxed until the starting material was consumed. Then

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

• comparing the intensities of the ACD values, the reliability of determining the absolute configurations can be guaranteed. Further application of the method to amines with more complex structures is currently in progress. Experimental General methods All reagents and solvents were commercially available and