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

• transformed into rockogenin 12-methanesulfonate-3-pivalate (89) by reduction and mesylation. Heating to reflux in anhydrous pyridine afforded the rearrangement to the C-nor-D-homo isosteroid skeleton 90 with an exocyclic 13,18-double bond in 5 steps from hecogenin acetate (see Scheme 29). In a five-step

• corresponding to deprotonation at C14 was observed. The elimination to the enal did not occur spontaneously but required heating of the corresponding C12-mesylate, hinting at the ring strain accompanied by formation of the double bond in the trans-hydrindane system. The enal was subjected to a Wittig

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

• –transmission spinner stage (1 rps sample rotation speed) and measured in transmission mode using Cu Kα (1.541874 Å) radiation in the 2.0000–34.9964° 2θ range with 0.0131° 2θ step size and continuous gonio (θ/θ) scan in 1 measurement cycle. 45 kV accelerating voltage and 40 mA anode heating current were used

• . 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

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

• 10.3762/bjoc.21.203 Abstract Various 5-arylidene derivatives were prepared via a Knoevenagel condensation-type reaction of aromatic/heteroaromatic aldehydes with rhodanine or thiazolidine-2,4-dione (TZD) catalyzed by EDA/AcOH under microwave heating. This convenient methodology is broad in scope (49

• condensation-type reaction using ethylenediamine (EDA) as catalyst in AcOH under microwave (μw) heating. This convenient methodology is broad in scope, provides the condensation products in high yields (up to 99%), with a reasonable catalyst loading (10 mol %) in only 30 minutes. This approach also enabled the

• . Photophysical studies indicated a fluorescence mechanism via intramolecular charge transfer (ICT). Results and Discussion Synthesis of 5-arylidene derivatives under microwave heating To find the ideal reaction conditions for the synthesis of 5-arylidene derivatives, benzaldehyde (1a) and rhodanine (2a) were

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

• example, an amphiphilic poly(methyl methacrylate)-based polymer modified with calix[4]pyrrole was found to form micelles in water that capture anions from caesium salts and can be precipitated from solution upon heating [11]. Similarly, a hydrogel composed of poly(vinyl alcohol) cross-linked by a “Texas

Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• reaction of 87 was employed, generating both the kinetic product 88 and the desired thermodynamic product 89. Heating 88 promoted a retro-Diels–Alder/Diels–Alder equilibrium, favoring the more stable isomer 89. Palladium-catalyzed hydrogenation of the 1,2-disubstituted alkene in 89, followed by Mo(CO)6

• Suzuki and co-workers in 2021 [44]. Their work proposed that this core structure could be generated from a highly oxidized allo-cedrane moiety through a tandem retro-Claisen/aldol reaction. Beginning with compound 100, a 6-step sequence afforded ortho-quinone 101 (Scheme 10). Heating 101 promoted an

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

• tandem approach preparing 7–12 ranged from 43–85%, which were similar to running the deprotection and cycloaddition reactions sequentially. Pd-catalyzed annulation using a modification of previously reported reaction conditions [46] under microwave irradiation instead of thermal heating converted 1,5

• thermal heating conditions [46] was successful for preparing these compounds. Yields of annulation reactions for the naphthalene-containing analog 31 (65%) was once again appreciably higher than that of the quinoline and isoquinoline derivatives 32–36 (31–51%), but there appeared to be no significant

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

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

• heating, to membrane permeabilization and dye release (Supporting Information File 1, Figures S12 and S13). In LUVs composed solely of EYPC, azobenzene photoisomerization in rotaxane 1 leads to 70% sulforhodamine B release (Table 1, Figure 4b, and Supporting Information File 1, Figure S14), comparable to

• rotaxane 1-Z would convert to 1-E over that timescale. Nevertheless, the results clearly show that heating above Tm enhances release. We next evaluated the effect of light irradiation on rotaxane 1 in DPPC. At 25 °C, the initial addition of 1-Z resulted in only a 3% release after 5 minutes. Irradiation at

• same amount of DMSO but no axle over five irradiation cycles alternating 370 nm and 467 nm light. As seen in Figure 7a, the release occurs only in vesicles containing axle 3, ruling out nonspecific effects such as membrane degradation from direct light exposure or solvent heating (HEPES buffer and

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

• photoredox catalysis) processes [8][9][10]. Cyclobutenone (A) is a versatile C4 synthon [11] – its [2 + 2] photocyclization yields B, featuring a strained bicyclo[2.2.0]hexane unit [12], which can fragment to form C (Figure 1a) [13][14]. However, competitive C1–C4 bond cleavage under irradiation or heating

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

• 30% and a selectivity of 70% at −100 °C (Scheme 21). 2.3 Wolff rearrangement The Wolff rearrangement is the transformation of α-diazoketones into acids or their derivatives through heating, catalysis, or UV irradiation in the presence of water, alcohols, ammonia, amines, etc. The Wolff rearrangement

• intermediate. The Wolff rearrangement was carried out by heating 132 in collidine and BnOH to obtain trans-hydrindane 133 as a single diastereomer with a yield of 73% (Scheme 23). In the work of Ding et al. [68], an elegant synthesis of (−)-pavidolide B (134) was described using the Wolff rearrangement. In

• the perhydrindanic structure. In contrast, the use of Al-H-Na-Lar pillared clay [90] as a heterogeneous catalyst and heating in 2-nitropropane at 100 °C induced angular methyl migration with formation of the halimanic bicyclic system 203 [90]. The acid-induced rearrangement of the drimanic epoxide 201

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

• laurate can be readily purified by vacuum distillation at the end of the reaction and safely reused. The synthesis of the corresponding cycloaddition products 3a–u was achieved by heating equimolar amounts of nitrone and maleimide in methyl laurate at 80 °C for the times indicated in Table 4. The

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

• under heating furnished chiral spiroindolylpyrroles in excellent yields and enantioselectivity (Scheme 1, path d) [11]. Moreover, a copper-catalyzed reaction of oxindole-derived alkenes with acetophenone O-acetyl oxime has also been employed to construct the spiroindolylpyrrole scaffold (Scheme 1, path

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

• , 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

• is suppressed, and the macrocycle becomes effectively immobilized. The process is reversible upon heating. Later, Tron and co-workers synthesized a [2]rotaxane containing a barbiturate moiety in the axle, which serves as a template for a reversible clipping approach [84]. The macrocycle precursor is

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

• . Before use, samples of H2, G2W1–G2W4 were repeatedly washed with water to remove TFA (monitored by 19F NMR) and activated by grinding and heating overnight at 90 °C under high vacuum. Experimentally, we incubated equimolar amounts (7.2 μmol) of each host with aqueous solutions of each dye (240 μM, 1 mL

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

• were previously used for the synthesis of 7-nitroindole derivatives: heating in polyphosphoric acid (PPA) at 80 °C [24][25]. However, our attempt was not successful. Experiments with zinc chloride, the most commonly used Lewis acid catalyst in Fischer indole syntheses, also failed under various

• performed using the method described in the literature [18], i.e., by heating compounds 5a,b with ketones 6a–e in the presence of bismuth nitrate pentahydrate catalyst and PPA in methanol at 110 °C in a closed vial (Scheme 1, method B). In the synthesis of asymmetric hydrazones 7a,c,f,h, the major product

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

• ), tert-butyl isocyanide (3a), and TMSN3 (4) in 2 mL of MeOH. After heating the reaction mixture at 40 °C for 12 h, the solvent was removed and changed to 2 mL of MeCN followed by heating at 130 °C for 2 h (Scheme 3A). However, no desired product was detected in the reaction mixture. The functional groups

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

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

• charged solar thermal fuels for deicing tests [74], showing effective ice removal capability under green light irradiation (Figure 7a). Wang et al. developed a photostimulated self-heating wristband [94] that elevates surface temperature from 29 °C to 44 °C upon blue light irradiation, protecting users

• irradiation (550 nm). Figure 7a was reprinted with permission from [74] Copyright © 2020 American Chemical Society. This content is not subject to CC BY 4.0. (b) Real-time infrared thermal imaging images of a charged self-heating wristband under blue light irradiation (450 nm). Figure 7b was reprinted from

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

• -triazoles, pyruvic acid, and salicylaldehydes were studied under different conditions. Upon conventional heating, benzotriazolooxadiazocine-5-carboxylic acids were formed in the three-component reactions as single reaction products. Upon ultrasonic activation or mechanical stirring at room temperature, the

• -triazoles, salicylaldehydes, and pyruvic acid were studied under different reaction conditions. In particular, it was found that the three-component reaction of an equimolar mixture of 5-amino-3-methylthio(methoxy)-1,2,4-triazole 1a,b, salicylaldehydes 2a–f, and pyruvic acid (3) under conventional heating

• behavior in this MCR. In the case of 3-carbomethoxy- and 3-(trifluoromethyl)-5-amino-1,2,4-triazoles the treatment with pyruvic acid and salicylaldehydes under thermal heating in different solvents (AcOH, DMF, n-butanol), instead of oxygen-bridged compounds gave a mixture of unidentified products with

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

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

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

• ) ketone, which could be converted to the corresponding bis(4-hydroxybenzyl) ketone (25c) by heating at 200 °C for 15 min to 3 h in the presence of pyridinium chloride [22][24]. Herein, we also show that the EDC-mediated coupling of 4-(benzyloxy)phenylacetic acid readily yields 25b, which may be

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• . Heating of indole 9a with azirine 2a in the presence of 5 mol % of Ni(hfacac)2 afforded the desired annulation product 10 in 41% yield (Scheme 5). Unfortunately, we were unable to find conditions that allowed a similar reaction of NH-indole 9b to occur. At the same time, when Ni(hfacac)2 was replaced with

Azide–alkyne cycloaddition (click) reaction in biomass-derived solvent Cyrene^TM under one-pot conditions

• Zoltán Medgyesi and
• László T. Mika

Beilstein J. Org. Chem. 2025, 21, 1544–1551, doi:10.3762/bjoc.21.117

• capillary column (15 m × 0.25 mm × 0.25 µm) using H2 as a carrier gas. For the analysis, 10 μL of the reaction mixture was dissolved in 1 mL of ethyl acetate, followed by adding 10 μL toluene as the internal standard. Heating profile of GC–FID analysis: The initial temperature was 100 °C and was hold for

• 0.5 min. Heating rate: 40 °C/min up to the final temperature of 270 °C. The final temperature was held for 4.25 min. The water content of CyreneTM was measured on a Methrom 684 KF Coulometer at Balint Analitika Ltd, Budapest, Hungary. CyreneTM was purchased from Sigma-Aldrich Kft. Budapest, Hungary

Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Marcin Palusiak,
• Heinz Heimgartner,
• Marta Denel-Bobrowska and
• Agnieszka B. Olejniczak

Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113

• regioselectivity in high yields. Upon heating to 65 °C in toluene solution, in analogy to the well-known compounds 2a and 2b, they extruded N2 and the in situ-generated reactive thiocarbonyl S-methanides 1c and 1d, in absence of any trapping reagent, underwent 1,3-dipolar electrocyclization yielding the