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

• , ciglitazone, and rosiglitazone [9][10]. Rhodanine (2-thioxothiazolidin-4-one) derivatives exhibit a wide range of pharmacological activities, including antiviral [11], antimalarial [12], antimicrobial [13], anti-inflammatory [14], anticancer [15], antidiabetic [16], antibacterial [17], and antifungal [18

• -stimulating phosphatase-1 (JSP-1) [26], and anthrax lethal factor protease [27]. Thiazolidine-2,4-dione (TZD) derivatives also display diverse pharmacological activities, including antibacterial [28], antifungal [29], antidiabetic [30], antitubercular [31], antiparasitic [32], anti-inflammatory [33

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

• their high potential for biological activity, such as anti-inflammatory, antimicrobial, immunomodulatory, neuroprotective, hepatoprotective, hypoglycemic, hypolipidemic, antioxidant, antispasmodic, antitumoral, antiviral, and antiallergic. The breadth of the biological action of these cyclopentanoids is

• measure the significance of the β-face methyl groups. The attractive synthesis of 3-ethyl-substituted betulinic acid derivatives with high cytotoxic and anti-inflammatory activity was described by Grishko et al. [35]. The 2,3-secotriterpenic 3-ethyl-3-ketone 46 was obtained in two steps from lupane α

• unprecedentedly highly oxygenated five-membered D-ring. These compounds exhibit potent anti-inflammatory and analgesic activity both in vitro and in vivo [44]. The synthetic method for the preparation of dactylicapnosines A (63) and B (64) was based on the known phenol 65 and involved the ring contraction of p

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

• : alkaloids; cyclic 1,3-dicarbonyl compounds; desymmetrization; enantioselective reduction; terpenoids; Introduction Terpenoids and alkaloids are two major classes of highly important natural products because they usually exhibit diverse and important biological activities, such as antitumor, anti

• -inflammatory, and antiarrhythmic effects etc., and show potential to be developed into drug candidates or novel medications for treating human diseases [1][2][3][4]. However, their scarcity in nature limits further research into their biological activities. Total synthesis is an important device to address the

Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design

• Daniil V. Khabarov,
• Valeria A. Litvinova,
• Lyubov G. Dezhenkova,
• Dmitry N. Kaluzhny,
• Alexander S. Tikhomirov and
• Andrey E. Shchekotikhin

Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161

• [2,1-b]quinazoline-6,12-dione) and its derivatives are particularly noteworthy as they demonstrate multiple biological activities, including antibacterial, antitumor, antifungal, antiviral, anti-inflammatory, antileishmanial, antiplasmodial, etc. [18][19]. The structurally isomeric class – pyrimido

• activities, including antiviral, antibacterial, anti-inflammatory, antitumor, and insecticidal properties. Notably, gramine [24] and other Mannich bases [25] exhibit a broad range of bioactivity, and structurally related compounds such as sumatriptan and rizatriptan have been approved for clinical use [24

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

• [40] activities. Furthermore, a quinoxaline-containing commercial drug, caroverine, has been proven effective in the treatment of tinnitus [41]. In addition, in vivo studies in mice and rats with various quinoxalinone derivatives have shown favorable analgesic and anti-inflammatory properties as well

• anti-inflammatory activity [49][50] (Scheme 1, pathway A). In an earlier study by our research group, Sakhno et al. [51] described a three-component Doebner-type reaction involving KGA, aromatic aldehydes, and 3-amino-5-methylisoxazole, which led to the formation of [2-aryl-4-hydroxy-1-(5

Understanding the origin of stereoselectivity in the photochemical denitrogenation of 2,3-diazabicyclo[2.2.1]heptene and its derivatives with non-adiabatic molecular dynamics

• Leticia A. Gomes and
• Steven A. Lopez

Beilstein J. Org. Chem. 2025, 21, 2007–2020, doi:10.3762/bjoc.21.156

• been employed to release carbon monoxide at relatively safer doses in biological systems using photoresponsive CO-releasing molecules (photo-CORMs) [4] because these have shown anti-inflammatory activity [5][6]. Photochemical denitrogenation of azoalkanes has been utilized in the stereoselective

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• , antibacterial, and anti-inflammatory activities [10][11][12][13]. In the field of optoelectronics, especially with 2,4-diarylquinoline derivatives, extensive studies have highlighted their applicability in organic light-emitting diode (OLED) systems as functional materials [14][15] and cutting-edge fluorescent

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

• developed a SAC4A grafted self-assembled peptide hydrogel for hypoxia-responsive controlled drug release in anti-inflammatory treatment of ischemic stroke (Figure 17) [125]. Following PBS induction, the peptide hydrogel was tailored to exhibit a rheological modulus and shear-thinning behavior similar to

Facile synthesis of hydantoin/1,2,4-oxadiazoline spiro-compounds via 1,3-dipolar cycloaddition of nitrile oxides to 5-iminohydantoins

• Juliana V. Petrova,
• Varvara T. Tkachenko,
• Victor A. Tafeenko,
• Anna S. Pestretsova,
• Vadim S. Pokrovsky,
• Maxim E. Kukushkin and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 1552–1560, doi:10.3762/bjoc.21.118

• pharmacophore, and molecules containing this group exhibit a wide range of biological activities, including antitumor, anti-HIV, anti-obesity, anti-inflammatory, antidiabetic, anticancer, and antitubercular properties [1][2]. Among these molecules, bicyclic compounds with the dihydrooxadiazole connected to

• known for their anticancer, anti-inflammatory, antidiabetic, antimicrobial, adrenoreceptor modulating, anticonvulsant, antiplatelet, anti-HIV, and other activities [5][6]. Modifying hydantoins at the N1, N3, and C5 positions make it possible to achieve better pharmacological properties. In this paper

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• acyclic compounds [19][20][21][22][23]. Furthermore, the enaminone structural moiety represents the key framework of many drug classes, including antibiotic (1) [24], anti-inflammatory (2) [25], antinociceptive (3) [26], anticonvulsant (4) [27], antitubercular (5) [28], and antitumor (6) [29] agents

Heterologous biosynthesis of cotylenol and concise synthesis of fusicoccane diterpenoids

• Ye Yuan,
• Zhenhua Guan,
• Xue-Jie Zhang,
• Nanyu Yao,
• Wenling Yuan,
• Yonghui Zhang,
• Ying Ye and
• Zheng Xiang

Beilstein J. Org. Chem. 2025, 21, 1489–1495, doi:10.3762/bjoc.21.111

• biosynthesis; P450 oxidation; synthesis; Introduction Fusicoccanes are a family of 5-8-5 tricyclic diterpenoid natural products that are produced by bacteria, fungi, algae, and plants (Figure 1a) [1][2][3][4][5][6][7]. Fusicoccanes possess a broad range of biological activities, including anticancer, anti

• -inflammatory, antimicrobial, antiparasitic, and plant growth regulating activities. For instance, cotylenin A (1) and fusicoccin A (2) function as molecular glues to stabilize the interactions between 14-3-3 proteins and their binding partners in plant and animal cells [8][9][10][11][12]. It has been reported

Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper

• Andrei Paraschiv,
• Valentina Maruzzo,
• Filippo Pettazzi,
• Stefano Magliocco,
• Paolo Inaudi,
• Daria Brambilla,
• Gloria Berlier,
• Giancarlo Cravotto and
• Katia Martina

Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108

• anti-inflammatory activity [8]. Moreover, they can be applied in disorders of the central nervous system, such as insomnia and Alzheimer’s disease [9][10]. The preparation of 2-aminobenzoxazoles classically proceeds via cyclocondensation reactions from pre-functionalised precursors, or via the C2

Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

• Alexander S. Budnikov,
• Igor B. Krylov,
• Fedor K. Monin,
• Valentina M. Merkulova,
• Alexey I. Ilovaisky,
• Liu Yan,
• Bing Yu and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96

• various synthetically useful transformations, including alkene synthesis via Horner–Wadsworth–Emmons reaction [14][15], heterocycle construction [16][17], and the synthesis of chiral β-amino and β-hydroxy phosphonic acids [18][19]. Furthermore, they exhibit metal-complexing abilities [20], and anti

• -inflammatory [21][22] as well as enzyme inhibition activities [23][24][25][26]. Traditionally, β-ketophosphonates were prepared via Arbuzov reaction [27], acylation of alkylphosphonates [28], and hydration of alkynylphosphonates [29][30][31]. However, these methods have several drawbacks, including low atom

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• ]. Since then, borrelidin has been recognized for its potential as a cancer therapeutic [3][4][5], exhibiting anti-inflammatory [6], anti-angiogenic [7][8][9], antimicrobial [10], antifungal [11][12][13], and antimalarial activities [14][15]. Since then, borrelidin has been recognized for its potential as

• a cancer therapeutic, exhibiting anti-inflammatory, anti-angiogenic, antimicrobial, antifungal, and antimalarial activities. While Keller-Schierlein first determined its chemical structure, Anderson later confirmed its absolute configuration using X-ray crystallography [16]. During the screening of

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• (TXA2) synthetase inhibition [10], antinociceptive [11], histone deacetylase inhibition [12], α-glucosidase inhibition [13] , tyrosinase inhibition [14], allelochemical [15], anticonvulsant [16], antioxidant [17], antiplatelet aggregation [18], anti-inflammatory [19], and UV absorption [20]. Cinnamic

Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline

• Benedek Batizi,
• Patrik Pollák,
• András Dancsó,
• Péter Keglevich,
• Gyula Simig,
• Balázs Volk and
• Mátyás Milen

Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79

• : it acts as an antioxidant [28], shows antibacterial activity against Mycobacterium tuberculosis [31], has antiproliferative effects against triple-negative breast cancer [32], serves as an agent against Parkinson's disease [29], and possesses skin anti-inflammatory properties [33]. Notably, the

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• subfamilies: ring intact limonoids, ring-seco limonoids, rearranged limonoids and N-containing limonoids (Figure 1). Moreover, these molecules exhibit a remarkable pharmacological portfolio encompassing anticancer, antimicrobial, anti-inflammatory, and insect antifeedant activities [7][8][9], positioning them

4-(1-Methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones: synthesis, anti-inflammatory effect and in silico approaches

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Luc Van Meervelt,
• Do Thi Thao and
• Nguyen Minh Thong

Beilstein J. Org. Chem. 2025, 21, 817–829, doi:10.3762/bjoc.21.65

• hydrogen bonding with Cys200. These results underscore the potential of 4-(1-methylamino)ethylidenepyrrolidine-2,3-diones, especially compound 5e, as promising scaffolds for the development of anti-inflammatory agents targeting iNOS-related pathologies. Keywords: anti-inflammatory pyrrolidine-2,3-dione

• pyrrolidine-2,3-dione derivatives could inhibit biomacromolecules (DNA, BSA, mPGES-1 or CDKs) and consequently, enable them to be candidates for Alzheimer's disease [11], anti-inflammatory [12][13][14][15][16][17], and antitumor drug discovery [12]. Furthermore, pyrrolidine-2,3-diones are also important

• -disubstituted pyrrolidine-2,3-diones as scaffolds for the development of anti-inflammatory agents targeting iNOS-related pathologies. Results and Discussion Synthesis of 4-(1-methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones 5a–e The reaction between 4-acetyl-3-hydroxy-1,5-disubstituted-3

Total synthesis of (±)-simonsol C using dearomatization as key reaction under acidic conditions

• Xiao-Yang Bi,
• Xiao-Shuai Yang,
• Shan-Shan Chen,
• Jia-Jun Sui,
• Zhao-Nan Cai,
• Yong-Ming Chuan and
• Hong-Bo Qin

Beilstein J. Org. Chem. 2025, 21, 601–606, doi:10.3762/bjoc.21.47

• , including insecticidal, antibacterial, anti-inflammatory, analgesic, and neurotrophic activities [3]. In 2013, Wang’s group isolated (±)-simonsol C from star anise, which features a unique 6/5/6 tricyclic benzofuran structure [4]. They found that it exhibits biological activity that promotes neuronal

Sequential two-step, one-pot microwave-assisted Urech synthesis of 5-monosubstituted hydantoins from L-amino acids in water

• Wei-Jin Chang,
• Sook Yee Liew,
• Thomas Kurz and
• Siow-Ping Tan

Beilstein J. Org. Chem. 2025, 21, 596–600, doi:10.3762/bjoc.21.46

• Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany 10.3762/bjoc.21.46 Abstract The hydantoin scaffold is renowned for its wide-ranging biological activities, including antibacterial, antiviral, anticancer, anti-inflammatory, and anticonvulsant effects. In

• antibacterial [1], antiviral [2], anticancer [3], anti-inflammatory [4], and anticonvulsant [5]. Hydantoins were traditionally accessed from amino acids by conversion to urea derivatives followed by cyclization (Urech reaction) or from carbonyl compounds through the cyanohydrin intermediate (Bucherer–Bergs) [6

Synthesis, characterization, antimicrobial, cytotoxic and carbonic anhydrase inhibition activities of multifunctional pyrazolo-1,2-benzothiazine acetamides

• Ayesha Saeed,
• Shahana Ehsan,
• Muhammad Zia-ur-Rehman,
• Erin M. Marshall,
• Sandra Loesgen,
• Abdus Saleem,
• Simone Giovannuzzi and
• Claudiu T. Supuran

Beilstein J. Org. Chem. 2025, 21, 348–357, doi:10.3762/bjoc.21.25

• biologically active useful candidates. NSAIDs (non-steroidal anti-inflammatory drugs) currently approved like piroxicam [12], meloxicam [13], and other derivatives of these two are well known for their activities [5]. 1,2-Benzothiazines are highly bioactive moieties and have been explored as antibacterial [14

• autoimmune diseases [18], osteoarthritis [29], hemorrhage [25], and cardiac diseases [30]. Pyrazole moieties have a wide spectrum of pharmacological efficiencies. One known example is celecoxib®, a clinically used anti-inflammatory and COX-2 enzyme-inhibiting drug [31]. In some cases, inclusion of a pyrazole

• [9]. Pyrazolobenzothiazines have also been synthesized and explored as p38α MAPK inhibitors [35]. In 2015, Sabatini and co-workers synthesized a novel series of pyrazolobenzothiazines and identified as new generation anti-inflammatory agents. Two of these compounds are reported with an IC50 of 0.5 µM

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• representative studies include antibacterial, anti-inflammatory, antioxidant, selective inhibitor of COX-2 [34], and anti-HIV activity [35]. In this context, even though indole is considered a privileged scaffold present in some anticancer agents [36], a few examples of methanesulfonylindoles are studied as

• cytotoxic compounds. For example, a cytotoxic effect was found in CAL 27 cells, presumably through a mechanism of TNF-α inhibition in vitro, which could be related to the anti-inflammatory effect identified in several studies of NSAIDs that inhibit cancer cell viability in vitro [37][38]. In another study

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• abilities has been verified by mathematical calculations. Keywords: decarbonylation–oxidation; hydroperoxide; 2-hydroxybenzophenone; transition-metal-free; UV-protection; Introduction Benzophenone compounds are ubiquitous in nature, and show biological activities such as anti-inflammatory, antiviral, and

Efficient modification of peroxydisulfate oxidation reactions of nitrogen-containing heterocycles 6-methyluracil and pyridine

• Alfiya R. Gimadieva,
• Yuliya Z. Khazimullina,
• Aigiza A. Gilimkhanova and
• Akhat G. Mustafin

Beilstein J. Org. Chem. 2024, 20, 2599–2607, doi:10.3762/bjoc.20.219

• are widely used in pharmacology due to their pronounced biological activities and low toxicities. The introduction of a hydroxy function into uracil and pyridine molecules has led to compounds with antioxidant, anti-inflammatory, and immunomodulatory activity (3-hydroxy-6-methyl-2-ethylpyridine, 5

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• heteroarylations [75]. For example, the heteroarylations of the nonsteroidal anti-inflammatory drug pranoprofen was accomplished, producing the desired product in 67% yield only within 30 min (Scheme 51). The f-EPC system integrates the advantages of electrophotocatalysis and flow chemistry, providing a rapid and