Synthesis, biological and electrochemical evaluation of glycidyl esters of phosphorus acids as potential anticancer drugs

• Almaz A. Zagidullin,
• Emil R. Bulatov,
• Mikhail N. Khrizanforov,
• Damir R. Davletshin,
• Elvina M. Gilyazova,
• Ivan A. Strelkov and
• Vasily A. Miluykov

Beilstein J. Org. Chem. 2025, 21, 1909–1916, doi:10.3762/bjoc.21.148

• synthetic organic chemistry and pharmaceutical applications due to their diverse biological activities. In this study, we synthesized three novel glycidyl esters of phosphorus acids 1–3 via the condensation of chlorophosphine oxides or phosphorus oxychloride with glycidol in the presence of a base

Preparation of spirocyclic oxindoles by cyclisation of an oxime to a nitrone and dipolar cycloaddition

• Beth L. Ritchie,
• Alexandra Longcake and
• Iain Coldham

Beilstein J. Org. Chem. 2025, 21, 1890–1896, doi:10.3762/bjoc.21.146

• an important class of compounds with significant biological activities. Spirocyclic derivatives are present in a variety of natural products. We describe here the formation of spirooxindoles using an intermolecular nitrone cycloaddition reaction. The nitrone dipole was prepared in situ by cyclisation

• ]. Representative examples are shown in Figure 1. The alkaloid alstonisine has antimalarial activity, with IC50 7.6 μM against Plasmodium falciparum [5]. However, the biological activities of most of the Alstonia alkaloids are currently unknown, despite the potential of spirooxindoles for drug discovery [6]. This

[3 + 2] Cycloaddition of thioformylium methylide with various arylidene-azolones in the synthesis of 7-thia-3-azaspiro[4.4]nonan-4-ones

• Daniil I. Rudik,
• Irina V. Tiushina,
• Anatoly I. Sokolov,
• Alexander Yu. Smirnov,
• Alexander R. Romanenko,
• Alexander A. Korlyukov,
• Andrey A. Mikhaylov and
• Mikhail S. Baranov

Beilstein J. Org. Chem. 2025, 21, 1791–1798, doi:10.3762/bjoc.21.141

• tetrahydrothiophenes are known to exhibit different biological activities [8]. However, to date the use of this reagent in the synthesis of spirocyclic derivatives to our knowledge is underinvestigated [26][27]. Results and Discussion In this work we present a systematic study of [3 + 2] cycloaddition of thioformylium

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• chiral products, e.g., biological activities and utility as chiral organocatalysts or ligands, warrants greater attention. We anticipate that considerable efforts in these directions would be crucial for advancing this field and fully unlocking the synthetic potential of isocyanides in the preparation of

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

• another cycle via the single quaternary carbon atom C5 demonstrated significant biological activity, greater than analogs with non-spiro-bonded cyclic fragments [3][4]. Hydantoin derivatives also exhibit a wide range of biological activities. Compounds containing the hydantoin pharmacophore group, are

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

• by its natural source, Cladosporium sp. 501-7W, due to the loss of its ability to proliferate during preservation [17]. The important biological activities and complex structures of fusicoccane diterpenoids have inspired several total syntheses, which range between 15 and 29 steps [18][19][20][21][22

• , the diverse biological activities and complex structures of fusicoccane diterpenoids have stimulated multiple elegant chemical syntheses. In contrast to these approaches, we harnessed the biosynthetic machinery of brassicicenes to produce brassicicene I in an engineered A. oryzae strain. Brassicicene

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• vitro [19]. As for natural occurrence of oxetanes, they are relatively uncommon, and an extensive review has recently been published by Dembitsky which explored the structural features and biological activities of oxetane-containing natural products [20]. Some of the most famous examples are taxol [21

• E [30] and daphnepapytone C [31] from the 2020s (Figure 4). Most of these compounds possess intriguing biological activities and selected examples from this list are discussed in more detail in chapter 4 with regards to their isolation, bioactivity and a recent total synthesis. The aim of this work

• transformations of 3-oxetanone leading to advanced oxetane building blocks. In chapter 3, we review the reactivity of oxetanes with regards to ring openings and ring expansions including both symmetric and enantioselective variants. Finally, chapter 4 covers isolations, biological activities and total syntheses

A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones

• Ashutosh Nath,
• John Mark Awad and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92

• modifications of MCRs could generate novel and complex molecular scaffolds [1][2][3][4][5][6][7][8]. Some MCR adducts generated from Ugi, Passerini, Gewald, Biginelli, and Groebke–Blackburn–Bienaymé (GBB) reactions have been modified to form chemically diverse heterocyclic scaffolds with potential biological

• activities [9][10]. Imidazo[1,2-a]pyridine and isoquinolinone-kind scaffolds are privileged rings which can be found in drug molecules such as zolimidine [11], zolpidem [12], alpidem and antiemetic drug 5-HT3A antagonist palonosetron [13] (Figure 1). Imidazopyridine-fused isoquinolinones have been developed

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

• Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Negeri Semarang, Semarang, Central Java 50229, Indonesia 10.3762/bjoc.21.91 Abstract Borrelidin, a naturally occurring antibiotic, has attracted considerable interest due to its diverse biological activities and complex molecular

• ]. Moreover, several derivatives have been synthesized by Moss et al. (2006) [42], Wilkinson et al. (2006) [43], Sunazuka et al. (2013) [44], Hahn et al. (2014) [45], Laschat et al. (2016) [46], and Huang et al. (2018) [47]. This demonstrates that borrelidin, with its remarkable biological activities and

Pd-Catalyzed asymmetric allylic amination with isatin using a P,olefin-type chiral ligand with C–N bond axial chirality

• Natsume Akimoto,
• Kaho Takaya,
• Yoshio Kasashima,
• Kohei Watanabe,
• Yasushi Yoshida and
• Takashi Mino

Beilstein J. Org. Chem. 2025, 21, 1018–1023, doi:10.3762/bjoc.21.83

• Isatin is a well-known natural indole derivative. Due to the broad biological activities of its derivatives, extensive research has been conducted on their synthesis. Furthermore, the isatin framework is a versatile starting material for various transformations, including multicomponent reactions and the

Synthesis of pyrrolo[3,2-d]pyrimidine-2,4(3H)-diones by domino C–N coupling/hydroamination reactions

• Ruben Manuel Figueira de Abreu,
• Robin Tiedemann,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2025, 21, 1010–1017, doi:10.3762/bjoc.21.82

• . Electron-donating N,N-dimethylaminophenyl substituents led to bathochromically shifted absorption and emission spectra accompanied by strongly elevated fluorescence quantum yields (up to 83%). Further studies will be devoted to the synthesis of novel polycyclic uracil derivatives with potential biological

• activities. Development of drugs based on pyrrolopyrimidines: A: Cadeguomycin. B: Tubercidin. C: Toyocamycin. D: Batzelladine A. E: Sangivamycin. F: Pemetrexed. G: Immucillin H. H: TAK-285 (tyrosine kinase inhibitor). UV–vis absorption (left) and emission (right, λex = 300 nm) spectra of compounds 4a, 4j, 4k

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• [2,1-a]isoquinolin-3(2H)-one framework is a pivotal core structure among various pyrrolo[2,1-a]isoquinoline alkaloids, exemplified by (+)-crispine, annosqualine, and erysotramidine, among others (Scheme 5) [29]. These bioactive alkaloids exhibit a broad spectrum of biological activities, including

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

• controlling inflammatory diseases. There have 2-pyrrolidinone subunit-containing compounds which exhibited promising biological activities [7]. For example, stemoamide extracted from Stemona tuberosa Lour, a Chinese traditional medicine, has been used in the treatment of asthma and tuberculosis [8][9]. (2S)-N

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• have a low oxidation potential and can be oxidized quickly to act as a catalyst (Scheme 5). Acridines are important nitrogen-containing heterocyclic compounds used as the building block for preparing medicinally active compounds. The conjunction of phosphorus with acridine increases its biological

• activities. Budnikova et al. [50] reported a C–P bond formation via the reaction of acridine compounds with trialkyl phosphites in electrochemical conditions without metal catalysts and strong oxidizing reagents, conducting selective C9 phosphorylation with high yield. The reaction was carried out in an

Copper-catalyzed domino cyclization of anilines and cyclobutanone oxime: a scalable and versatile route to spirotetrahydroquinoline derivatives

• Qingqing Jiang,
• Xinyi Lei,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2025, 21, 749–754, doi:10.3762/bjoc.21.58

• the desired product. Keywords: copper catalysis; cyclobutane-fused tetrahydroquinolines; domino cyclization reaction; green synthesis; Introduction Tetrahydroquinolines (THQs) represent a privileged scaffold in medicinal chemistry, exhibiting a broad spectrum of biological activities and serving as

• therapeutic development. The strained cyclobutane ring, in particular, acts as a versatile and conformationally constrained building block, enabling the construction of complex molecular architectures with potent biological activities [22]. Despite their promise, the synthesis of cyclobutane-fused THQs

Semisynthetic derivatives of massarilactone D with cytotoxic and nematicidal activities

• Rémy B. Teponno,
• Sara R. Noumeur and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 607–615, doi:10.3762/bjoc.21.48

• Massarilactones constitute a rare class of polyketides produced mainly by endophytic fungi. Given that semisynthetic derivatives often exhibit biological activities greater than those of the substrates, seven previously unreported derivatives of massarilactone D, compounds 2–8, were synthetized by acylation with

• products can serve as effective scaffold for the design and synthesis of derivatives with improved biological activities [5][6][7]. Massarilactones are produced by marine and endophytic fungi and bear close biogenetic similarity to several other fungal PKS1-derived metabolites including rosigenin, the

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

Vinylogous functionalization of 4-alkylidene-5-aminopyrazoles with methyl trifluoropyruvates

• Judit Hostalet-Romero,
• Laura Carceller-Ferrer,
• Gonzalo Blay,
• Amparo Sanz-Marco,
• José R. Pedro and
• Carlos Vila

Beilstein J. Org. Chem. 2025, 21, 533–540, doi:10.3762/bjoc.21.41

• for the synthesis of tertiary trifluoromethyl carbinols [6][7]. In this context, trifluoromethyl carbinols constitute a key structural motif present in a wide range of molecules with important biological activities (Figure 1) [8][9][10], on account of the distinctive properties of organofluorine

New tandem Ugi/intramolecular Diels–Alder reaction based on vinylfuran and 1,3-butadienylfuran derivatives

• Yuriy I. Horak,
• Roman Z. Lytvyn,
• Andrii R. Vakhula,
• Yuriy V. Homza,
• Nazariy T. Pokhodylo and
• Mykola D. Obushak

Beilstein J. Org. Chem. 2025, 21, 444–450, doi:10.3762/bjoc.21.31

• and step-economy, making them promising for future commercial applications. Partly hydrogenated isoindoles and their derivatives exhibit broad biological activities and are considered privileged motifs in medicinal chemistry [20][21]. These compounds, when condensed with aromatics or heterocycles

Unraveling aromaticity: the dual worlds of pyrazole, pyrazoline, and 3D carborane

• Zahra Noori,
• Miquel Solà,
• Clara Viñas,
• Francesc Teixidor and
• Jordi Poater

Beilstein J. Org. Chem. 2025, 21, 412–420, doi:10.3762/bjoc.21.29

• ; Introduction Pyrazoles and 1,2-diazoles are five-membered aromatic heterocyclic compounds that have garnered significant attention in recent years [1][2][3]. While these compounds are rarely found in nature, they exhibit a wide range of biological activities, making them highly useful in pharmaceutical

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• [16][17]. Indole derivatives, including those with conjugated aromatic and alicyclic rings, are of considerable interest because of their diverse biological activities (antibacterial, antimicrobial, anticancer, antidiabetic, etc.) [18][19][20][21][22]. For this reason, the synthetic goal of this work

Antibiofilm and cytotoxic metabolites from the entomopathogenic fungus Samsoniella aurantia

• Rita Toshe,
• Syeda J. Khalid,
• Blondelle Matio Kemkuignou,
• Esteban Charria-Girón,
• Paul Eckhardt,
• Birthe Sandargo,
• Kunlapat Nuchthien,
• J. Jennifer Luangsa-ard,
• Till Opatz,
• Hedda Schrey,
• Sherif S. Ebada and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 327–339, doi:10.3762/bjoc.21.23

• Metarhizium that are known as biocontrol agents against insect pests like mosquitoes and ticks in agricultural and forestry applications [5]. Secondary metabolites produced by entomopathogenic fungi have garnered attention due to their diverse biological activities, encompassing antimicrobial, antiviral, and

Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• under the umbrella of C1 chemistry was to provide a straightforward access to the privileged scaffold of fused heteroannulated pyrimidones, which demonstrate a broad range of biological activities [28][29][30][31][32][33][34][35], including use as emissive nucleoside analogues [36][37][38]. Moreover

• synthesis was efficient and rapid as the final adducts could be isolated only by precipitation. In addition, the reactions were performed in a parallel setup using custom-made metal blocks. Specifically, thienopyrimidine and thienopyrimidone derivatives exhibit a range of biological activities, i.e

• of aliphatic and aromatic substituents (Scheme 4). Pyrimidines and pyrimidone-bearing indole derivatives are crucial in organic chemistry because of their extensive use as bioactive compounds with a wide array of significant biological activities (DB03074, DB03304, DB08131) [70][71][72]. In a similar

Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• for the late-stage transformation of C–F bonds, as demonstrated by the orthogonal activation of both aromatic C–F and C–Br bonds, thereby facilitating the synthesis of complex 2-arylbenzofurans. Given that natural and synthetic 2-arylbenzofurans often exhibit considerable biological activities and are

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• ) ligand 4 were reported by Cowley and co-workers in 2010 [14]. In addition to heterocyclic fluoranthene analogues, highly oxygenated benzo[j]fluoranthenes are commonly encountered fungal natural products with important biological activities [15]. Bulgarein (5) is an example of such a benzo[j]fluoranthene