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

• the discovery of small molecule modifiers for investigating and engineering proteins. Keywords: covalent probes; molecular diversity; rhodium carbenoids; Introduction Diverse sets of reactive probes can facilitate the discovery of chemical tools and drugs that chemically modify protein targets [1][2

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

• agent; glycidyl ester; electrochemical evaluation; phosphorus-containing drug; Introduction Phosphorus-containing drugs represent a crucial category of therapeutic agents, extensively utilized in clinical practice due to their diverse pharmacological properties and applications [1][2][3][4]. These

• , phosphine oxides, and bisphosphonates, allows for tailored modifications that enhance selectivity, bioavailability, and reduce potential side effects [8][9][10][11][12][13]. This versatility makes them valuable not only as drugs but also as intermediates in synthetic organic chemistry, facilitating access

• to a wide array of molecular targets [14][15][16]. The importance of phosphorus-containing drugs extends beyond their therapeutic applications; they also play a pivotal role in addressing specific medical conditions such as chronic kidney disease (CKD) [17][18]. The synthesis of organophosphorus

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

• in active pharmaceutical ingredients, therapeutic agents, and agrochemical formulations [1][2][3][4][5][6][7][8][9]. Around 60% of recently FDA-approved drugs contain heterocyclic compounds, with quinoline recognized as a key structural motif due to its significant anticancer, antifungal

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

• of controlled-release technologies, with the aim of offering a reference for the utilization of aromatic macrocycles in drug-controlled release applications. Keywords: aromatic macrocycle; controlled-release drug delivery systems; stimulus response; supramolecular chemistry; Introduction Drugs are

• defined by the Food and Drug Administration (FDA) as substances used for diagnosing, relieving, treating, or preventing diseases [1]. Traditional forms of drugs typically have a systemic effect, reaching both healthy and diseased areas, leading to a lack of selectivity, low bioavailability, and limited

• efficacy [2][3][4]. Nowadays, there are technologies that can better confine the action of drugs to where they are needed. Drug delivery is a technology that administers drugs to patients, which can specifically increase the concentration of drugs in certain parts of the body, thereby enhancing the

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

• electrostatically complementary negative and positive faces. These interactions are mediated through electrostatic hydrogen bonds. This "Janus-like" polarity also facilitates interactions with ions, particularly sodium and chloride. These findings contribute valuable insights for the rational design of drugs and

• insights can guide the prediction of molecular properties, paving the way for the design of innovative applications. Fluorinated cyclopropanes, with their unique electronic and structural characteristics, hold significant potential in the development of new drugs, advanced materials like liquid crystals

Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• potent gonadotropin-releasing hormone receptor antagonists with potential application as anticancer drugs [25] and as nucleoside analogs with antiviral potency [26]. According to the reaction mechanism proposed by Elliott et al., the aza-Diels–Alder reaction of vinyloxazoline S-6 with TsNCO is a step

pH-Controlled isomerization kinetics of ortho-disubstituted benzamidines: E/Z isomerism and axial chirality

• Ryota Kimura,
• Satoshi Ichikawa and
• Akira Katsuyama

Beilstein J. Org. Chem. 2025, 21, 1568–1576, doi:10.3762/bjoc.21.120

• various fields, such as functional materials, biological probes, and drugs. a) Structural features of DiBA. b) Resonance structure of the amide moiety of DiBA. c) Molecular form and protonated structure of ortho-disubstituted benzamidine. Rotational barriers of 2-bromo-N,N,6-trimethylbenzimidamide and its

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

• oxindole [3][8][9], chrysenequinone [10], cycloheptatriene [11][12], thiazole [13], and matrine-type alkaloids [14]. The hybrid pharmacophore design is a frequently employed approach in the development of potential antitumor and other drugs [15][16]. This method involves the merging of two distinct

• developed for existing spiro systems to the new hybrid drugs. In this work a similar modification of imidazolidine derivatives was performed for the first time for the synthesis of spiro-hydantoins. The title reactions were carried out using two alternative techniques for the generation of the reactive 1,3

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

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

• bioactive compounds. According to the DrugBank there are more than 250 approved drugs classified as amides [2]. Just recently, between February 2021 and June 2022, sixteen anticancer drugs containing an amide bond have been approved by the U.S. FDA [3]. Consequently, the preparation of amides has garnered

N-Salicyl-amino acid derivatives with antiparasitic activity from Pseudomonas sp. UIAU-6B

• Joy E. Rajakulendran,
• Emmanuel Tope Oluwabusola,
• Michela Cerone,
• Terry K. Smith,
• Olusoji O. Adebisi,
• Adefolalu Adedotun,
• Gagan Preet,
• Sylvia Soldatou,
• Hai Deng,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2025, 21, 1388–1396, doi:10.3762/bjoc.21.103

• Biochemistry, Federal University of Lafia, Nigeria 10.3762/bjoc.21.103 Abstract Pseudomonads strains represent a promising source of bioactive compounds with potential pharmaceutical applications. The necessity to find new drugs is underscored by the increased concern over antimicrobial resistance in the

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

• (Scheme 2). HHP-assisted acylation of NH and OH groups: synthesis of acetaminophen (paracetamol) and acetylsalicylic acid Tylenol® and Aspirin® are two popular drugs used as pain killers as well as antipyretics [45]. Although their industrial production is straightforward, these syntheses include the use

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

• a marine or hypersaline environment natural products library to identify potent drugs, a putatively novel metabolite co-produced with borrelidin was discovered, expanding the potential for new borrelidin derivatives. This led to the formation of the so-called “borrelidin family” (Table 1), with

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

• patient isolates in African geographies [1][2]. P. falciparum isolates have also been detected in various global regions with at least some measure of resistance to all frontline ACT partner drugs [1][2]. New chemotherapeutics are urgently needed to manage malarial disease and forestall or circumvent ACT

Gold extraction at the molecular level using α- and β-cyclodextrins

• Susana Santos Braga

Beilstein J. Org. Chem. 2025, 21, 1116–1125, doi:10.3762/bjoc.21.89

• , heat, oxidation, and hydrolysis. Owing to their properties, cyclodextrins are frequently applied in pharmaceutical formulations with low-soluble or unstable drugs [28][29][30], in cosmetic formulations [31][32], and in the food industry [33][34]. The vast majority of guests in these applications are

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

• 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

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

• dihydrochloride salt of the alkaloid has been tested in vivo in rats, cats, and rabbits as an antiarrhythmic agent, demonstrating superior efficacy compared to the commercially available drugs quinidine and novocainamide [34]. N-Methylbrevicarine, a semi-synthetic derivative of the alkaloid, has been screened in

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

• greater than 0.9 is generally considered as the indicator of high permeability [28]. The analysis revealed that all five potential drugs demonstrated high permeability across the Caco-2 membrane, with log Papp values ranging from 1.082 to 1.472. Furthermore, intestinal absorption is classified as

• ellipsoids at the 30% probability level. The intramolecular hydrogen bond is shown as red dashed line. The bioavailability radar of studied compounds 5a–e. The interactions of potential drugs 5a–c in the active site of enzyme iNOS. The interactions of potential drugs 5d and 5e and control drug (DEX) in the

• compounds 5a–e. Molecular docking results of potential drugs with enzyme iNOS. Supporting Information Supporting Information File 44: Synthetic procedures, compound characterization, X-ray crystallographic data, bioassay for NO inhibition, NMR and ESI-HRMS spectra for all reported compounds

Acyclic cucurbit[n]uril bearing alkyl sulfate ionic groups

• Christian Akakpo,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 717–726, doi:10.3762/bjoc.21.55

• biomedical applications including as a solubilizing excipient for anticancer agents and as an in vivo sequestrant to reverse the biological activity of neuromuscular blocking agents, anesthetics, and drugs of abuse (e.g., methamphetamine and fentanyl) [54][55][56][57][58][59][60]. As a result of their

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

• ]. This molecule is a ring-expanded analogue of proline, and derivatives of it are found within several natural products and drugs. The pucker of the six-membered ring of 96 is quite important for bioactivity, because different puckers project the carboxyl substituent in different orientations (equatorial

• –C–N alignment is anti, the effect is stronger and the pKaH will be lowered by ≈2 log units. Clearly it is important to bear this in mind when utilising fluorine to optimise the properties of nitrogen-containing drugs. Having concluded our examination of fluorinated amines, let us now focus upon some

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

• -natural amino acids are pivotal in protein engineering and drug development. Over 30% of approved small‑molecule drugs today contain non‑canonical amino acid building blocks [1][2]. In peptide and protein engineering, non‑natural amino acids significantly increase the respective range of tools used to

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• cyclic amino acids are common structural motifs in the design of small-molecule drugs and peptidomimetics [1]. For example, the clinically used anesthetics carfentanil (1) and remifentanil (2), the FDA-approved antipruritic medication defelikefalin (3), and the arginase inhibitor 4 [2] possess cyclic α,α

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• , combining the specificity of antibodies with the potency of cytotoxic drugs to enhance therapeutic efficacy while minimizing off-target effects. The development of new chemical methods for bioconjugation is essential to generate ADCs and to optimize their stability, efficacy, and safety. Traditional

• designed in the context of cancer therapy [1], which combines the precision targeting of monoclonal antibodies (mAbs) with the therapeutic effects of cytotoxic drugs [2]. The ADCs are thus designed to deliver potent cytotoxic agents selectively and directly to cancer cells while minimizing damage to

• , systemic cancer chemotherapies often involve combinations of drugs. Combination regimens improve treatment outcomes by producing synergistic anticancer effects and slowing the development of drug-resistant cell populations. Researchers aim to replicate combination regimens by developing techniques for

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

• Remy B. Teponno Sara R. Noumeur Marc Stadler Department Microbial Drugs, Helmholtz Centre for Infection Research, Inhoffenstraße 7, 38124 Braunschweig, Germany and Institute of Microbiology, Technische Universität Braunschweig, Spielmannstraße 7, 38106 Braunschweig, Germany Department of Chemistry

Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• ongoing challenge. Cryptophycins are a class of cyclic depsipeptides renowned for their high cytotoxicity in the picomolar range often combined with efficacy against multidrug-resistant tumour cell lines. However, cryptophycins failed as stand-alone drugs in cancer treatment, and their naturally occurring