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

• scaffolds for several synthetic or natural compounds [5]. Five-membered heterocycles include the thiazolidinone nucleus, characterized by two heteroatoms and a carbonyl group on the fourth carbon, as seen in compounds like rhodanine and thiazolidine-2,4-dione derivatives (Figure 1). These privileged

• spectra (Scheme 7b). A remarkable feature of the 13C NMR spectra of compounds 3n and 4n in DMSO is the attenuation/absence of peaks corresponding to the carbon atoms at the ortho and meta positions of the six-membered ring. It is known that quaternary carbon atoms have very long relaxation times, but this

• behavior is not expected from hydrogen-bonded carbon atoms in aromatic rings. Since peak intensities depend on spin-lattice relaxation times, the absence of peaks implies some degree of molecular rigidity, which could be related to two factors: the viscosity of DMSO and the conjugation between the six

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

• 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

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

• sterically congested sesquiterpenoids isolated from the genus Illicium. Illisimonin A stands out as one of the most structurally intricate members of this family, featuring a novel bridged tricyclo[5.2.1.01,5]decane carbon framework designated as the “illisimonane” skeleton. This core ring system is further

• have been isolated from this genus, among which Illicium sesquiterpenes represent a prominent group. Since the first isolation of anisatin in 1952 [1], more than 100 Illicium sesquiterpenes have been isolated from over 40 species of Illicium [2]. Based on their carbon skeletons, they can be classified

• ][23][24][25]. In 2017, Yu and co-workers isolated a new Illicium sesquiterpene, namely illisimonin A, from the fruits of Illicium simonsii [26]. Unlike other Illicium sesquiterpenes, illisimonin A features an unprecedented bridged tricyclo[5.2.1.01,5]decane carbon framework that incorporates a highly

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

• pericyclic reactions [31][32][33][34][35][36][37][38][39][40][41][42][43][44], to control the formation of the crucial C5 chiral center precisely. Subsequent oxidative cleavage of the carbon–carbon double bond introduced in the Diels–Alder reaction, followed by an intramolecular aldol reaction, efficiently

• the simultaneous construction of four quaternary carbon centers (C1, C4, C5, and C12) and the core AB bicyclic skeleton, markedly improving synthetic efficiency. Subsequent oxidative desymmetrization of the C14–C15 olefin in (±)-33 established the sterically hindered C11 quaternary carbon center. An α

• stereocenters characteristic of the target molecule, the authors strategically implemented this methodology. This approach efficiently established two carbon–carbon and four carbon–oxygen bonds while introducing four contiguous stereocenters, successfully assembling the highly functionalized AB ring system

Ni-promoted reductive cyclization cascade enables a total synthesis of (+)-aglacin B

• Si-Chen Yao,
• Jing-Si Cao,
• Jian Xiao,
• Ya-Wen Wang and
• Yu Peng

Beilstein J. Org. Chem. 2025, 21, 2548–2552, doi:10.3762/bjoc.21.197

• the formation of inter- or intramolecular carbon–carbon bonds under mild conditions [9][10][11][12], and strategically applied this method for the divergent syntheses of some natural products [13][14][15][16][17]. Herein, we report our recent advance to a total synthesis of (+)-aglacin B (2), which

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

• 19 was moderate because the anomeric carbon at C7 is associated with an acid-sensitive acetonide group. The structural determination of the major product 19a was accomplished by comprehensive NMR spectroscopy and further unambiguously confirmed by X-ray analysis (see Supporting Information File 1 for

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

• ). The proton signals of the NH₂ and CH₂S groups of the isothiouronium substituents were clearly observed at 9.04 ppm and 4.23 ppm, respectively. Additionally, the carbon signal of the CH₂S group appeared at 169.3 ppm. The NMR signals, consistent with a fully symmetric structure, evidenced the exhaustive

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

• linker are highlighted in red. Sequences for RNA hairpins and PNA ligands used for binding studies. Major-groove view of hydrogen-bonding interactions in the (A) Db1*U–A triplet, (B) Db2*U–A triplet, (C) Db2*C–G triplet, and (D) Db3*U–A triplet. Carbon, hydrogen, oxygen, and nitrogen are labelled in

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

• construction of the tetracyclic core of Aspidosperma alkaloids. Our method involves an Ir-catalyzed PET reaction of K for the stereoselective formation of the cis-configured BC bicyclic core with an all-carbon quaternary center [25][26]. Computational studies suggest that the observed tandem PET reaction of K

• the formation of benzyl radical IN2, which has a boat-like seven-membered ring. This structural feature may facilitate formation of the C19–C12 bond, even in the presence of critical steric hindrance between the C5 quaternary carbon and the indole moiety. Further DFT investigation proved challenging

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

• point = −64 °C). To minimize the setup needed and handling we decided to utilize the two-chamber reaction vessels introduced by Skrydstrup and co-workers [19], which were originally designed for use with carbon monoxide reactions [20] and are now commercially available under the tradename COware (Figure

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

• with two attached side chains – of seven (α-chain) and eight (β- or ω-chain) carbon atoms. Their main physiological role is to maintain the homeostatic harmony of the organism [1][2]. Among the terpenoids containing cyclopentane in their structure, we should mention jatrophane or latirane diterpenoids

• and 51 showed high cytotoxic activity (IC50 1.38–15.91 μM). 2 Rearrangements with 1,2-carbon migration Rearrangements with 1,2-carbon migration are widely used in the synthesis of natural compounds [37]. These include benzilic acid and semipinacol-type rearrangements, reactions promoted by thallium

• [52] achieved high regioselectivity and stereospecific construction of contiguous all-carbon quaternary centers through an oxidative ring contraction of cyclic α-formyl ketones by the action of H2O2. This reaction is easy to perform, environmentally friendly, and does not require expensive catalysts

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

• pathway (Scheme 4). Initial Fe(II)-mediated reductive cleavage of the N–O bond in the ketoxime acetate generates an iminyl radical. This is followed by a 5-exo-trig cyclization to form a carbon-centered radical. Final single-electron oxidation by Fe(III) delivers the desired spirocyclic product. All

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• vibralactone, a potent inhibitor of pancreatic lipase, is reported. The synthesis of the challenging all-carbon quaternary center within the cyclopentene ring was achieved through intramolecular alkylidene carbene C–H insertion. Keywords: alkylidene carbene; C–H insertion; total synthesis; vibralactone

• cyclopentene ring containing an all-carbon quaternary center [14], and inhibits pancreatic lipase with an IC50 of 0.4 µg/mL. Several congeners with varying oxidation state, as well as related β-hydroxy acids or esters have also been isolated from the culture broth of the basidiomycete [15][16][17][18][19][20

• -lactone with an all-carbon quaternary center and two trisubstituted olefin moieties. It is therefore not surprising that this compound has attracted considerable interest from both the chemical biology and synthetic chemistry communities. Sieber and co-workers disclosed that vibralactone can target ClpP1

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

• -stilbenes have 5-membered rings fused to the carbon–carbon double bond, are more photostable, and undergo reversible photoisomerization with higher efficiency (Figure 2) [75]. Notably, their cis isomer exhibits higher thermal stability than that of other commonly used photoswitches, such as azobenzene. This

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

• stereochemical inversion of the Norrish–Yang reaction. This achieved efficient construction of benzofuranone-based 4,5-spirocycles with contiguous all-carbon quaternary centers, offering a conformational regulation protocol for stereocontrol in complex polycyclic systems. 1.3 Avarane-type meroterpenoids In 2024

• ingeniously leverages the high selectivity of photochemical reactions and the strain-release property of rearrangement reactions, enabling the precise construction of multiple stereocenters in one step and overcoming the synthetic challenges posed by contiguous quaternary carbon centers and sterically

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

• ], and non-conventional adsorbents [14]. Although activated carbon is widely used, its ability to capture polar compounds is limited and the regeneration process is complex and energy-intensive [15]. In work that stimulated supramolecular chemists to enter the game, Dichtel and co-workers demonstrated

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

• for the construction of carbon–carbon and carbon–heteroatom bonds. Unlike many ionic reactions, radical reactions are often functional group tolerant and carried out under mild, neutral conditions, avoiding harsh acidic or basic conditions that can promote epimerization or decomposition of the product

• . Additionally, radical chemistry offers opportunities to achieve transformations that may not proceed via two-electron processes. Radicals can be generated through several different approaches, summarized in Figure 1A. The use of organostannanes to generate carbon-centered radicals was formerly commonplace but

• 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

• solvent-controlled selective syntheses of two polycyclic compounds (Scheme 6) [13]. Using PdCl2 as the catalyst and DMF as the solvent, substrate 22 underwent a 6-endo-dig cyclization and subsequent enone insertion, forming a palladium–carbon bond intermediate. Protonolysis yielded isocoumarin-fused

• -catalyzed cyclization strategy for the synthesis of 1,2- and 2,3-fused quinazolinones, which was controlled by the angle strain of a key carbon atom in the substrate (Scheme 30) [43]. Experimental results showed intramolecular cyclization depended on the hybridization state of the carbon adjacent to

• quinazolinone's amino group. When this carbon atom was in a sp2 hybridization state, the C3 position of the indole attacked the inner side of the triple bond under the action of a gold catalyst, leading to a 6-exo-dig cyclization to yield 1,2-fused quinazolinones 146 (Scheme 30, path a). When the carbon atom was

Research towards selective inhibition of the CLK3 kinase

• Vinay Kumar Singh,
• Frédéric Justaud,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Blandine Baratte,
• Thomas Robert,
• Stéphane Bach,
• Chada Raji Reddy,
• Nicolas Levoin and
• René L. Grée

Beilstein J. Org. Chem. 2025, 21, 2250–2259, doi:10.3762/bjoc.21.172

• ). Second, molecular docking using DYRK1A crystal structure was used to understand the unexpected binding on the DYRK kinases (Figure 6). Surprisingly, another lysine (K175) is also located near the acidic group of VS-77 (at 3.2 Å between the carbonyl carbon atom and nitrogen from amine). This residue is

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

• ureas 1 proceeded smoothly in an undivided cell (reticulated vitreous carbon (RVC) anode, Pt cathode, 5 mA), forming the desired indoles 2 in high yields. The reaction showed good compatibility with various functional groups like phenyl, furyl, alkenyl and alkyl at the acetylene moieties, producing 2a–d

• alkynylation of electron-deficient benzamide. In 2022, Ye presented an electrochemical synthesis of isoindolinone through 5-exo-dig aza-cyclization of 2-alkynylbenzamide (Scheme 9) [208]. By applying carbon cloth as anode, Pt as cathode and n-Bu4NOAc as electrolyte, the 5-exo-dig/6-endo-dig cyclization of 2

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

• biomass shows how renewable carbon sources can replace non-renewable chemicals in important industrial processes [18][19][20]. Many, if not most, biobased platform molecules contain carbonyl groups. Carbonyl compounds have unique electrophilic and nucleophilic reactivity which make them central players in

• for the synthesis of GA and GCA using activated carbon deposited Cu catalysts and different biomass-derived polyols as feedstock with exceptionally high atom utilization ≈93% and up to 90% yield (Scheme 1) [28]. Glycolaldehyde (GCA), the smallest sugar molecule, was used by Sels et al. for the

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

• The desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds is a powerful tool for the construction of ring systems bearing multiple stereocenters including all-carbon quaternary stereocenters, which are widely useful chiral building blocks for the total synthesis of structurally

• shortage of natural product sources. Nevertheless, the asymmetric total synthesis of terpenoid and alkaloid natural products presents significant challenges due to their complex and diverse ring systems and the presence of multiple stereocenters, including all-carbon quaternary stereocenters. Consequently

• , (−)-glaucopine C, and (+)-allocyathin B2 The cyrneine diterpenoids represent an important subfamily of cyathane diterpenoids which possess a common 5-6-7 fused tricarbocyclic core with two all-carbon quaternary stereocenters. Many impressive syntheses have been reported to date [18][19][20][21][22][23][24][25

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

• studies of these molecules indicated that they exhibit a broad-spectrum activities including antifungal, insecticidal, plant pathogenic properties and phytotoxic activity. Structurally, these molecules basically contain an isocoumarin ring system and a five-carbon side chain. The side chain could further

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

• stored thermal energy in a controlled manner, a phase designated "energy discharging" (Figure 1). The core advantages of such closed-loop systems are primarily manifested in their reversible cycling capability, carbon neutrality characteristics, transportation convenience, and on-demand heat generation

• applications, highlighting key contributions in the field. Discussion Nanocarbon-based azobenzene polymer solar thermal fuels Nanocarbon-based azobenzene polymer solar thermal fuels are constructed by grafting azobenzene moieties onto carbon nanotube [43][44][45] or reduced graphene oxide (RGO) templates

• . 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

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

• sufficiently electrophilic carbonyl carbon atom with the elimination of triphenylphosphine oxide via the aza-Wittig reaction. It should be noted that the best method for the isolation of quinoxalinones 9 was column chromatography using an elution gradient of hexane/ethyl acetate 3:1 to hexane/ethyl acetate 1:2

• 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