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

• ]. The use of visible light as an energy source has significantly expanded the scope of organic molecule activation and its application in organic synthesis or medicinal chemistry [12], thereby driving the fast development of various photocatalytic transformations. Among these advances, dual catalysis

• radical-/radical cross-coupling performed between intermediates C and E. The reaction of acyl fluoride 4 in the presence of Cs2CO3 and NHC to produce benzoate A and the formation of some reactive intermediates are shown in Scheme 2. These methods will find suitable application in medicinal chemistry and

• used for late-stage modification of bioactive compounds, including natural products. These developments will find suitable applications in medicinal chemistry for introducible organosilyl groups (Scheme 5) [55]. A visible-light-induced Friedel–Crafts acylation of arenes and heteroarenes was reported by

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

• attracted increasing interest as numerous TT-based compounds were proposed as promising candidates in medicinal chemistry due to their diverse pharmacological profiles including antitumor, antiviral, antimicrobial, enzymatic and phototherapeutic activities [15]. Among them, TT-2-carboxanilides exhibit

• robust approach to a wide range of 3-substituted thiophene-2,5-dicarboxylates. These intermediates are of interest as valuable building blocks for the synthesis of more complex thiophene derivatives in both materials and medicinal chemistry contexts. The synthetic routes to 3-hydroxy-substituted TT

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

• activities, spiro[indoline-3,2'-pyrrolidines] have attracted substantial interest in medicinal chemistry, prompting the development of diverse synthetic strategies. Several methodologies have been reported for the synthesis of substituted spiro[indoline-3,2'-pyrrolidines] (Scheme 1), which can be broadly

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

• half-life: t1/2 ≈ 60 min) threshold, compound 3e qualifies as a suitable candidate for subsequent medicinal chemistry investigation [44]. The outcome somewhat elucidates the distinctive behavior of 3e in the aforementioned clogP–logk relationship: despite the expected elevated clogP, we obtained a

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

• heterocyclic scaffolds to obtain biologically interesting compounds (Scheme 1) [35][36][37][38][39][40][41]. The development of methods for the synthesis of triazole, tetrazole, piperazinone, and 1,4-benzodiazepine motifs are attractive from both synthetic and medicinal chemistry considerations [42][43][44][45

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

• quinoxalinones and Ugi reaction products may be valuable for organic synthesis and medicinal chemistry because the presence of a free carboxyl group makes them promising for use as building blocks for the construction of complex heterocyclic structures, including those using multicomponent reactions. Some

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• amino acids [8][9][10]. Sets of reactive probes are generally prepared using robust reactions, most usually amide formation, chosen from the toolkit that currently dominates medicinal chemistry [11] which may, in turn, limit probe structural diversity. We have developed a unified connective approach for

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

• into the synthesis, cytotoxic behavior, and biochemical reactivity of glycidyl esters of phosphorus acids. The results support their potential as reactive anticancer candidates and lay a foundation for future structure–activity relationship studies and further development in medicinal chemistry

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

• probes for sensing and bioimaging applications (Figure 1) [16][17]. Quinoline-derived metal complexes have also demonstrated broad utility, functioning as effective catalysts in organic synthesis and finding applications across medicinal chemistry, materials science, photovoltaics, and chemical sensing

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

Unique halogen–π association detected in single crystals of C–N atropisomeric N-(2-halophenyl)quinolin-2-one derivatives and the thione analogue

• Mai Uchibori,
• Nanami Murate,
• Kanako Shima,
• Tatsunori Sakagami,
• Ko Kanehisa,
• Gary James Richards,
• Akiko Hori and
• Osamu Kitagawa

Beilstein J. Org. Chem. 2025, 21, 1748–1756, doi:10.3762/bjoc.21.138

• chemistry but also medicinal chemistry [10][11][12][13]. For example, 3-(2-bromophenyl)-2-methylquinazolin-4-one (I), which has a high rotational barrier about the N3–Ar bond, is known as mebroqualone possessing GABA agonist activity (Figure 1) [14][15]. Our group has been exploring asymmetric synthesis of

• interaction as an alternative to hydrogen bonding and has been widely used as an important supramolecular tool in broad fields such as materials science, crystal engineering, liquid crystals, synthetic organic chemistry and medicinal chemistry [22][23][24][25][26]. Typically, halogen bonding has been

Thermodynamics and polarity-driven properties of fluorinated cyclopropanes

• Matheus P. Freitas

Beilstein J. Org. Chem. 2025, 21, 1742–1747, doi:10.3762/bjoc.21.137

• Matheus P. Freitas Department of Chemistry, Institute of Natural Sciences, Federal University of Lavras, 37200-900, Lavras, MG, Brazil 10.3762/bjoc.21.137 Abstract Cyclopropane is a significant alicyclic motif, widely utilized in medicinal chemistry, while fluorination serves as a powerful tool

• prevents ring interconversion, unlike its larger analogs. It is widely used in pharmaceuticals and has attracted significant interest in medicinal chemistry, particularly when fluorinated [1][2][3][4][5][6]. The highly polar C–F bond in fluorinated cyclopropanes destabilizes the ring and alters its overall

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

• intermediates in the synthesis of several derivatives with important applications in medicinal chemistry. Furthermore, many marketed drugs feature the enaminone structural moiety. In this context, we have developed a photoredox and nickel catalytic system to rapidly forge the enaminone scaffold from 3

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

• . China Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, P. R. China Institute of Chemical Biology, Shenzhen Bay Laboratory, Shenzhen 518132, P. R. China 10.3762/bjoc

Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

• significant attention within organic and medicinal chemistry. Commonly, amide bonds are formed via the reaction of carboxylic acids or their derivatives with appropriate amines (Scheme 1A) [4]. Although this conventional approach is effective and straightforward, it usually suffers from harsh conditions and

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• of catalyst- and solvent-free processes is desirable. Chalcones are a privileged scaffold in medicinal chemistry and are used for the synthesis of a multitude of products [43]. The cyclization between chalcones and hydrazines usually occur via a C=O/NH2 condensation and a subsequent NH addition to

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

• Peter Gabko Martin Kalnik Maros Bella Institute of Chemistry, Slovak Academy of Sciences, Dúbravská cesta 9, 845 38 Bratislava, Slovakia 10.3762/bjoc.21.101 Abstract Oxetanes are 4-membered cyclic monoethers which have found important applications in medicinal chemistry as polar and metabolically

• ]. The first to recognise that these unique physicochemical properties may have valuable applications in medicinal chemistry were Carreira, Rogers-Evans, Müller and colleagues, who together reported that 3-substituted oxetanes can serve as isosteric replacements for carbonyl and gem-dimethyl groups

• methyls with an oxygen atom effectively eliminates its lipophilic character and reduces susceptibility to metabolic attack, while practically maintaining the molar volume. Because controlling polarity and metabolic stability is a major issue in medicinal chemistry, 3-substituted oxetanes have eventually

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

Enhancing chemical synthesis planning: automated quantum mechanics-based regioselectivity prediction for C–H activation with directing groups

• Julius Seumer,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2025, 21, 1171–1182, doi:10.3762/bjoc.21.94

• reliable regioselectivity predictions that are essential for accelerating innovation in materials science and medicinal chemistry. Keywords: C–H activation; chemical synthesis planning; directing groups; quantum mechanics; regioselectivity prediction; Introduction The activation and functionalization of

• the potential to significantly accelerate the discovery and optimization of new synthetic routes, thereby impacting materials science and medicinal chemistry by facilitating the synthesis of novel compounds with high precision and efficiency. Pattern Matching Tomberg et al. [9] assembled a look-up

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

• applications in medicinal chemistry. Chemical structure of borrelidin (1). Synthetic strategy for Morken’s C2–C12 intermediate 20 as reported by Uguen et al. [41]. Preparation of monoacetates 37 and ent-38 by Uguen et al. [41]. Preparation of sulfones 27 and ent-27 by Uguen et al. [41]. Attempts to couple

Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-a]pyrazine scaffold

• Henry S. T. Smith,
• Ben Giuliani,
• Kanchana Wijesekera,
• Kah Yean Lum,
• Sandra Duffy,
• Aaron Lock,
• Jonathan M. White,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2025, 21, 1126–1134, doi:10.3762/bjoc.21.90

• resistant parasites [1]. Open Source Malaria (OSM) is a drug development and medicinal chemistry platform established by Matthew Todd formerly of The University of Sydney (currently at University College London) with funding from the product development partnership platform, Medicines for Malaria Venture

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

• in medicinal chemistry. For example, racemic compound 1 (Figure 1) was evaluated for its cytotoxicity against human breast cancer cells (MCF7) in comparison to the standard doxorubicin and exhibited excellent activity against the MCF7 cell line [12]. The optically active compound 2 also showed

Harnessing tethered nitreniums for diastereoselective amino-sulfonoxylation of alkenes

• Shyam Sathyamoorthi,
• Appasaheb K. Nirpal,
• Dnyaneshwar A. Gorve and
• Steven P. Kelley

Beilstein J. Org. Chem. 2025, 21, 947–954, doi:10.3762/bjoc.21.78

• Shyam Sathyamoorthi Appasaheb K. Nirpal Dnyaneshwar A. Gorve Steven P. Kelley Department of Medicinal Chemistry, University of Kansas, Lawrence, Kansas 66047, United States Department of Chemistry, University of Missouri—Columbia, Columbia, Missouri 65211, United States 10.3762/bjoc.21.78

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

• efficiency of reactions [14][15][16][17][18][19][20][21]. Organophosphorous compounds are essential materials with broad applications in medicinal chemistry, synthesis, agriculture, as ligands, and intermediates to prepare complex compounds. Due to their importance, scientists have introduced many studies in

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

• the growing significance of cyclobutane-fused tetrahydroquinolines (THQs) in biochemistry and medicinal chemistry [26][27][28], we have developed an efficient and convenient method for synthesizing cyclobutane-fused and conformationally constrained spirotetrahydroquinolines (STHQs) from arylamines and

• intermediates, followed by intermolecular cyclization and aromatization. The scalability of this method was demonstrated through a gram-scale reaction, highlighting its potential for practical applications in medicinal chemistry and drug discovery. Synthetic strategies for the construction of