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

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• , fragrance chemicals, organocatalysts, and peptides. This comprehensive review summarises developments in this field during the period 2010–2024. Keywords: conformational analysis; medicinal chemistry; organofluorine chemistry; stereoselective fluorination; Introduction In the art of origami, a

• . It should be noted that one of the reasons why C-2 fluorinated nucleosides (e.g., 67 and 68) have become especially popular in the field of medicinal chemistry [133][134][135][136][137], is that the presence of fluorine at C-2 confers enhanced stability towards hydrolysis, through destabilising the

Asymmetric synthesis of fluorinated derivatives of aromatic and γ-branched amino acids via a chiral Ni(II) complex

• Maurizio Iannuzzi,
• Thomas Hohmann,
• Michael Dyrks,
• Kilian Haoues,
• Katarzyna Salamon-Krokosz and
• Beate Koksch

Beilstein J. Org. Chem. 2025, 21, 659–669, doi:10.3762/bjoc.21.52

• spheres of protein engineering and medicinal chemistry. In the last decades, a large number of different synthetic strategies have been developed to produce a large variety of fluorinated amino acids. Still, obtaining fluorinated amino acids in great quantities can be challenging, or the corresponding

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

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• the cyclization process producing various highly diverse nitrogen-containing heterocycles, which are valuable scaffolds in medicinal chemistry [46]. Synthesis of non-aromatic heterocycles As stated above, DMSO can also hydrolytically decompose to formaldehyde. There are many examples of reactions in

• medicinal chemistry [58]. One of the most effective strategies for their synthesis is the addition of alkynes to imines or enamines, which is typically carried out under metal catalysis and elevated temperatures. This process requires the use of high boiling point solvents such as toluene, dimethylformamide

Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• our research program to tailor non-covalent RNA–small molecule ligands to their covalent counterparts. While “covalent drugs” have become a leading principle in medicinal chemistry in the “protein world” [35][36] – approximately 30% of all FDA-approved drugs form a covalent bond with their target

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

• environmentally friendly synthetic strategies, especially one-pot multicomponent and tandem reactions, are key to modern organic and medicinal chemistry [1][2][3][4][5][6][7] and have proven to be successful in generating diverse heterocyclic scaffolds, as highlighted in a recent book [8]. Multicomponent

• 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

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

• , makes them a suitable linker unit [34]. The leading example is paracetamol highlighting the utility of an amide containing scaffold in medicinal chemistry. A series of novel scaffolds adjoining benzothiazine with a pyrazole moiety has been reported with antioxidant activity and antibacterial potential

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• chemistry with significant potential in synthetic and biomedical fields. Keywords: green chemistry; medicinal chemistry; organic photochemistry; photocatalysis; red-light mediated transformations; Introduction Red-light-activated photocatalysis has recently gained significant interest as a tool for

• oxide by direct UV light absorption. However, this method, although simpler, is not suitable for the present medicinal application. The space and time-controlled release of bioactive compounds is an important tool in bio- and medicinal chemistry to study biochemical mechanisms or to develop new

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• as a vital pharmacophore in medicinal chemistry due to its special biological activity [11][12][13]. In particular, the tricyclic benzimidazole skeleton is ubiquitous in many bioactive compounds and therapeutic agents (Figure 1b) [14][15][16]. Recent studies have shown that fluorinated benzimidazole

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

• utilized numerous times in medicinal chemistry campaigns as hits, leads and eventually even drugs, such as 2-aminothiophenes, -quinolines and -indoles [42][43][44][45]. Synthetic exploitation The synthesis of the key cyanoacetamide building blocks was our primary objective. In a parallel setup, a variety

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• secondary amines via an N-acyl nitrene intermediate [77]. Amidines, found in biologically active compounds, have been widely investigated in medicinal chemistry due to their potent antiviral, antibacterial, anticancer, and other therapeutic properties [78][79][80][81]. As shown in Scheme 4, dioxazolones

• area of medicinal chemistry [93][94][95][96][97]. In 2018, Buchwald and co-workers unveiled the enantioselective synthesis of benzylic amines through the asymmetric Markovnikov hydroamidation of alkenes utilizing diphenylsilane in copper catalysis under mild reaction conditions [98]. Dioxazolones, as

Quantifying the ability of the CF₂H group as a hydrogen bond donor

• Matthew E. Paolella,
• Daniel S. Honeycutt,
• Bradley M. Lipka,
• Jacob M. Goldberg and
• Fang Wang

Beilstein J. Org. Chem. 2025, 21, 189–199, doi:10.3762/bjoc.21.11

• systems significantly enhances its hydrogen bond donation ability, a result consistent with theoretical calculations. We anticipate that this chemistry will be valuable for designing functional molecules for chemical biology and medicinal chemistry applications. Keywords: bioisostere; difluoromethyl

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6