Competitive cyclization of ethyl trifluoroacetoacetate and methyl ketones with 1,3-diamino-2-propanol into hydrogenated oxazolo- and pyrimido-condensed pyridones

• Svetlana O. Kushch,
• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess,
• Pavel A. Slepukhin,
• Alexandrina S. Volobueva,
• Vladimir V. Zarubaev and
• Victor I. Saloutin

Beilstein J. Org. Chem. 2025, 21, 2716–2729, doi:10.3762/bjoc.21.209

• three nucleophilic centers in 1,3-diaminopropan-2-ol (3), and because there is a need to increase diastereoselectivity of the cyclization process. Table 1 presents the optimization steps for the reaction conditions at various solvents and temperature. The reaction course was monitored by TLC and 19F NMR

• %) (Table 1, entry 10), with the formation of the cis,cis-bicycle 4acc as the predominant product (28%), while the proportion of hexahydrooxazolopyridones 5 was minimal (10%) compared to all other conditions. The highest content of hexahydrooxazolo[3,2-a]pyridin-5-one 5a was observed at room temperature in

Tandem hydrothiocyanation/cyclization of CF₃-iminopropargyl alcohols with NaSCN in the presence of AcOH

• Ruslan S. Shulgin,
• Ol’ga G. Volostnykh,
• Anton V. Stepanov,
• Igor’ A. Ushakov,
• Alexander V. Vashchenko and
• Olesya A. Shemyakina

Beilstein J. Org. Chem. 2025, 21, 2694–2702, doi:10.3762/bjoc.21.207

• hydrothiocyanation of ynones using KSCN in AcOH at 70 °C. They also demonstrated that the adducts of ynones are readily cyclized in situ via a second thiocyanation to form thiazine-2-thiones at a slightly higher temperature and for a longer time. Meanwhile the reaction with ynamides led to decyanative amido

• MSCN/acid system. In comparison to ynamides [19] and alkynehydrazones [22], whose adducts cyclize with the involvement of nitrogen functional groups at elevated temperatures and extended reaction times, the reaction of CF3-substituted iminopropargyl alcohols occurred at room temperature within 15 min

• formation and ratio of the products in contrast to the substituents in the imine fragment. NMR monitoring of reactions (1a/NaSCN/AcOH or 1g/NaSCN/AcOH in MeCN) did not allow to detect any intermediates even when the temperature was lowered to 0 °C. In the 1H and 19F NMR spectra the signals of products 2a

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

• resulted in a hydroxy group, which was oxidized to furnish Nazarov precursor 54 in 52% yield. Key step of this sequence was the photoinduced excited-state Nazarov reaction, which involved irradiation of 54 in dichloroethane at 366 nm for 30 min at room temperature. Remarkably, this method had been

Synthesis of new tetra- and pentacyclic, methylenedioxy- and ethylenedioxy-substituted derivatives of the dibenzo[c,f][1,2]thiazepine ring system

• Gábor Berecz,
• András Dancsó,
• Mária Tóthné Lauritz,
• Loránd Kiss,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2645–2656, doi:10.3762/bjoc.21.205

• amorphous character of the compounds exhibiting wide melting ranges (21b, 38d, 54f) were proven by XRPD measurements performed on a PANalytical Empyrean X-ray powder diffractometer at room temperature. Powder samples (without grinding) were placed between two Mylar foils in the sample holder at a reflection

• . Diffraction intensity was measured by a PIXcel 3D 1 × 1 area detector. Thermogravimetric (TG) curves of amorphous samples (21b, 38d, 54f) were measured by a TA Instruments Discovery TGA thermogravimetric analyzer in the 30–200 °C temperature range with a 10 °C/min heating rate using 11 to 12 mg sample in a

• 100 μL platinum pan in 25 mL/min nitrogen atmosphere. Melting properties of the amorphous samples (21b, 38d, 54f) were also studied by a TA Instruments Discovery DSC differential scanning calorimeter in the 25–120 °C temperature range with a 10 °C/min heating rate using 2.5 to 3.0 mg sample in a

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

• final natural product rhodexin A in one step. Just as expected, when directly subjecting 16 to the abovementioned conditions, rhodexin A was indeed afforded albeit in only 10% yield. The required longer reaction time and elevated temperature to achieve deprotection of the sugar motif resulted in an over

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

• disubstitution processes involving sulfur-to-nitrogen displacement, likely promoted by the nucleophilic character of the amine. These limitations are likely due to the reaction conditions employed, including the high temperature and acidic environment, which may favor side reactions over the desired

• experimental spectrum. In blue, suppressed or absent carbon atoms bound to hydrogen atoms. a) Visual impressions of the solvatochromic study in various solvents (10−5 M) after excitation with a natural light. b) UV–vis absorption spectra of 3n in different solvents (10−5 M) at room temperature. c) Normalized

• emission spectra of 3n in different solvents (10−5 M) at room temperature. d) Lippert–Mataga plot showing Stokes shift as a function of solvent orientation polarizability (Δf) for compound 3n. Photophysical study in aqueous solution under different pH values for compound 3n (10−5 M) at room temperature. a

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

• (Scheme 1). The latter reaction was also done using a 9:1 (w/w) ratio of a-SG to BU1, by treatment of a-SG with the macrocycle in DMF at ambient temperature (Scheme 1). The material was then isolated by filtration and washed with DMF and methanol. The prepared a-SG, SG-NHCO-BU1, and SG-BU1 materials were

• Silica gel (8.01 g) was dispersed in toluene (24 mL) and stirred under argon atmosphere, while heated up to 115 °C. Then, APTES (6 mL) was added, and the dispersion was stirred under inert atmosphere at elevated temperature for 5 h. After cooling, the dispersion was filtered, washed thoroughly with

• toluene, ethanol and acetone to remove unreacted APTES and dried in vacuo (50 °C) overnight in order to get a-SG [15][16]. Further, to prepare covalent SG-NHCO-BU1, a-SG (0.9 g) was suspended in DMF (15 mL) and shaken at ambient temperature for 30 min. BU1 (0.1 g, 1 equiv) was dissolved in a minimum

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

• enables the highly regioselective formation of meta-acylated ketone products 16 through a radical pathway. The NHC-catalyzed novel acylation was achieved using acyl fluorides 4 and electron-rich arenes 15 in the presence of NHC (20 mol %), photocatalyst (5 mol %), and Cs2CO3 in CH3CN at room temperature

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

• Instrument, Malvern, UK) equipped with a 633 nm laser, at a scattering angle of 90° and 25 °C temperature. The size of the particles was calculated from the diffusion coefficient using the Stokes–Einstein equation: where D is the diffusion coefficient, k is the Boltzmann constant, T is the absolute

• temperature, η is the solvent viscosity, and R is the solute radius. The zeta potential (Z) was calculated by using Henry’s equation where UE is the electrophoretic mobility, ζ is the dielectric constant, f(Ka) is the Henry’s function, and η is the viscosity. Biological assays: Cell viability was measured by

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

• pentacyclic ring system. A general downfield shifting of the entire set of signals by no less than 0.5 ppm supports the expansion of the overall aromatic π-system upon annulation. Aromatic signal symmetry for non-annulated compounds 12 and 42 show a lack of distinct rotational isomers at room temperature on

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

• selectivity for each of the remaining three mismatched base pair combinations. Binding studies were then performed by annealing each of the PNA strands (PNA1–PNA3) with the four RNA hairpins (HRP1–HRP4). UV thermal melting studies reveal an inflection point at the temperature where the PNA dissociates from

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

• formation of liquid-ordered (Lo) domains [16]. To further assess the effect of membrane rigidity on rotaxane behavior, we also studied LUVs composed solely of DPPC lipids, which form a highly ordered gel phase (Lβ) at room temperature due to their saturated acyl chains [17]. Rotaxane 1 was incorporated into

• ). Similarly, in LUVs composed of pure DPPC, which adopts a highly ordered gel phase (Lβ) at room temperature [17], minimal release was observed: 7% with rotaxane 1-E, 3% with rotaxane 1-Z, 6% with rotaxane 2, and 4% with axle 3 (Table 1, Figure 4a, and Supporting Information File 1, Figures S1d and S10). Our

• rotaxane 1 [15]. We examined whether dye release in DPPC LUVs could be enhanced by increasing the temperature above the lipid’s phase transition temperature (Tm = 41 °C) (Supporting Information File 1, S2.4). Below Tm, DPPC is in the gel phase (Lβ), where the hydrocarbon chains are highly ordered, forming

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

• 3) was used as solvent, the reduction of disulfide 3 with NaBH4 proceeded more efficiently at reflux for 2 h. The reaction mixture was then treated with K2CO3 and the alkylating agent at room temperature. The product was identified as the desired 3-benzylthio-substituted thiophene-2,5-dicarboxylate

• reactions, probably involving ester hydrolysis or alkylating agent decomposition, can be avoided by omitting the external base. In addition, Na2S2O4 was investigated as a reductant in a DMF/water 9:1 (v/v) mixture at room temperature (Table 2, entry 6). In the presence of both K2CO3 and the alkylating agent

• also gave product 7a in about 25% yield, along with the formation of a mixture of byproducts. It was found that the most favorable conditions for cyclization of compounds 4a, 4b, and 5a were their treatment with excess LiH in a solution of dry DMF at room temperature for 24 h. In this way, products 7a

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

• failed to enhance the product 2a yield (Table 1, entry 10). Attempts to optimize the reaction temperature did not yield improvements either (Table 1, entry 11). Control experiments confirmed that both the palladium catalyst and AgNO3 are essential for the reaction to proceed, as omission of either

• NiCl2/NaBH4 in methanol at room temperature, affording the corresponding amine 4 in 93% yield. To align with green chemistry principles, we employed a recently reported mechanochemical protocol by Ito and co-workers for the reduction of nitro compounds to amines [72]. Using this solvent-free method

• , 1.2 equiv). Then, the solvent 1,4-dioxane (2.0 mL) was added, and the reaction mixture was allowed to stir in a preheated oil bath at 120 °C for 24 h. Upon completion of the reaction time, the reaction mixture was cooled to room temperature and diluted with dichloromethane (10 mL). The reaction

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

• intense substrate decomposition (Table 1, entries 6–8). These results showed that MeCN is the best solvent for the reaction. Finally, we investigated the effects of an alternative N-substituent in the indole moiety, and the reaction time and temperature on the photocyclization results. Boc-substituted

• % (Table 1, entry 10) compared with that in entry 9 (42%). These results indicate that Cbz is a more effective protecting group than Boc under the profiled conditions. The effects of the reaction temperature on the outcome of the PET reaction of 9a were investigated. Among the conditions screened (Table 1

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

• [14][15][16][17]. Recently, 2,2,2-trifluoroacetaldehyde O-(aryl)oxime has been introduced as a precursor for trifluoroacetonitrile allowing to work under mild conditions at room temperature (Figure 1) [18]. Whether one prepares a precursor or the actual reagent, a separate setup is needed and hence

• conclusion, we have developed a simple and safe methodology for the on-demand ex situ generation of stoichiometric amounts of gaseous haloacetonitriles in a closed system at room temperature. The methodology is safe, robust, and operationally simple on a laboratory scale. The method was exemplified by the

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

• reaction yielded the desired product at room temperature with high regioselectivity and stereoselectivity (E/Z ratio >99:1). Notably, when chiral catalyst (cat.1) was used, the reaction afforded the axially chiral product 9 in 43% yield with 84% ee. The proposed mechanism proceeds as follows. Catalyst cat

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

• have been little studied, and are of interest to synthetic chemists. Thus, the interaction of (−)-metaphanine (70) with ammonia in CH3OH at room temperature led to the in situ formation of imine 72, which, as a result of an intramolecular aza-benzilic acid-type rearrangement, was converted in more than

• of α,β-epoxy ketone 197 using Lewis acids (Sc(OTf)3, TMSOTf, SnCl4, Yb(OTf)3, BF3·Et2O, BF3·CH3CO2H, BF3·THF, BF3·Bu2O) as a catalyst and different solvents (DCE, DCM, THF, CHCl3) has been described in [88]. By varying the temperature, solvent, and catalyst, optimal conditions were found for time

• reaction proceeded through two alternative directions with the formation of ring-contraction products – perhydrindane 202 (pathway I) and oxide 203, which has a halimanic bicyclic system (pathway II). The use of fluorosulfonic acid as a promoter at low temperature contributed to ring contraction to form

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

• experiment was conducted in which a series of organic solvents and water were subjected to solubility tests. For the purposes of this experiment, approximately 15 mg of nitrone was mixed with 1 mL of solvent in a 10 mL test tube at room temperature (22 °C). As demonstrated in Figure 8c, the solvents under

• percentage yields of compound 3a in each of the solvents that were considered in the current study. Furthermore, as indicated in Table 3, the vapour pressures of the solvents at a reaction temperature of 80 °C suggest their suitability to be used in cycloaddition processes, superseding the utilization of

• 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

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

• model ketone oxime acetate from β-3-indolyl ketone 3a using the previously described telescopic protocol [17]. This substrate was subjected to FeCl2-catalyzed spirocyclization in acetonitrile at room temperature, affording the desired spirocyclic product 4a in 70% yield as a mixture of diastereomers (dr

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

• bulky stoppers at both ends to prevent dethreading (Figure 1) [1][8]. Functionalization of the axle with recognition sites allows the macrocycle to shuttle between positions in response to external stimuli, including light, redox, temperature, pH, and reactions with chemicals such as carbodiimides [9

• , temperature, and acid–base stimuli. Additionally, this spiropyran-based rotaxane showed pronounced photochromic and fluorescent behavior in both powder and solid film under alternating UV/sunlight and visible light/heating conditions, highlighting its suitability for dynamic optical systems and anti

• 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

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

• blue LEDs at room temperature constructed a single diastereoisomer 23 in 90% yield. From 23, the ABCDE pentacyclic skeleton of phainanoids (27) was ultimately established via a Mitsunobu reaction, intramolecular nucleophilic substitution with in situ-generated aryllithium, and protecting group

• room temperature, delivering spiroacetal (S)-114 with complete retention of configuration (>99% ee). The subsequent one-pot acetylation generated (S)-115 in 83% overall yield over three steps from (S)-112. The following functional group manipulations of (S)-115 – including debenzylation/debromination

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

• enamine 9b, which was completely consumed in 6 hours at room temperature. Following acidic hydrolysis of the enamine, a mixture of α-trifluoromethylated ketone diastereomers was obtained, and subsequent epimerization with K2CO3 afforded 19 as a single stereoisomer in 48% yield. The equatorial position of

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

• control principles for gold catalysis. Temperature-controlled cyclization of 1,n-enynes Temperature, a pivotal thermodynamic parameter, not only governs reaction kinetics but also determines reaction pathways. Typically, kinetic product formation is favored at lower temperatures via pathways with reduced

• activation barriers, while thermodynamic products dominate under elevated thermal conditions. Recent advancements have yielded novel cyclization methodologies enabling pathway control through precise temperature regulation. In 2016, the Liao group reported a temperature-regulated strategy enabling the

• and hydrogen elimination then occurred, affording 3-azabicyclo[4.1.0]hepta-2,4-diene derivatives 156. In contrast, when the temperature was raised to 110 °C, intermediate 155 underwent a 6π electrocyclic ring-opening, which was trapped by in situ-generated cyanide ions to form 4,5-dihydro-3H-azepines

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

• 100 μM target concentration (1% DMSO). In the case of 7i, 7j, (E)-9a, and (E)-9b, samples were prepared with 50 μM (1% DMSO) and 100 μM (10% DMSO) target concentration, respectively. The plate was then sealed and shaken for 2 hours at room temperature. Each compound was investigated in 3 replicates

• PBS (pH 6.5) in each well to achieve 100 μM target concentration (1% DMSO). These samples were shaken for 1 hour at room temperature then filtered the same way as the kinetic solubility samples to make initial solutions for the PAMPA assay. The artificial membrane was fabricated by dissolving ʟ-α

•  4 was applied at a constant flow rate of 1.0 mL/min. The mass spectrometer operated in sensitivity mode with a capillary voltage of 3.0 kV, source temperature was 100 °C, and desolvation temperature was 350 °C. The cone gas flow was set to 0 L/h and desolvation gas flow to 800 L/h. LockSpray