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

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• ). The reverse effect was observed with amino-substituted 21. The photophysical properties of photoswitchable drugs in photopharmacology are usually determined in organic solvents. Their natural environment, however, is the aqueous phase. There is a risk of overestimating the performance of photochromic

• drugs because photoconversion to the active state usually drops considerably in water, and also half-lives are different. Light-activatable drugs based on N-acetyl diazocines are more hydrophilic than those derived from the parent system diazocine and corresponding azobenzenes. They retain their

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

• protein – this concept is underexplored in the field of RNA drugging [37]. Recent studies suggest that the validation of RNA–small molecule interactions [38][39][40], drug efficacy or the identification of off-target effects of approved drugs on the transcriptome [41][42] could greatly benefit from

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• huge interest in the study of ‘Glycomics’ or ‘Carbohydrate Chemistry.’ These truly elevated the recognition of carbohydrates from being mere building blocks to a frontier research topic towards the development of drugs and pharmaceuticals [12][13], diagnostic tools [14], artificial sweeteners [15

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

• possibility of carrying out subsequent stages of research and selecting promising compounds for the further development of anticancer drugs [30]. The study showed that the IC50 inhibitory concentration of 2-(1,1-dimethyl-1H-benzo[e]indolin-2-yl)-5,6,7-trichloro-1,3-tropolone (7a) against the A431 skin cancer

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

• progressing for decades. Reasons behind this issue include over-prescribing of FDA-approved drugs, agricultural use, rapid resistance development, and declining rates of novel antibiotic discovery [1]. In fact, the rate of discovery of new classes of antibiotics is low compared to the development of

• 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

• to inhibit p38α MAPK and 0.5 µM for TNF-α [10]. Pyrazolobenzothiazines containing a triazole moiety have also been studied as potential antibacterial drugs [7]. Other applications of N-substituted benzyl/phenyl acetamide pyrazolobenzothiazines include superoxide anion and DPPH radical scavenging

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

• Rita Toshe Syeda J. Khalid Blondelle Matio Kemkuignou Esteban Charria-Giron Paul Eckhardt Birthe Sandargo Kunlapat Nuchthien J. Jennifer Luangsa-ard Till Opatz Hedda Schrey Sherif S. Ebada Marc Stadler Department of Microbial Drugs, Helmholtz Centre for Infection Research GmbH (HZI) and German

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

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

• properties that can modify the activity and pharmacokinetic profiles of drugs [7]. Prominent examples include pantoprazole, a widely used proton-pump inhibitor (PPI) featuring a CF2H group; deracoxib, another drug that also incorporates a CF2H moiety in its structure; and a MET inhibitor specifically