Recent advances in the stereoselective synthesis of distal biaxially chiral molecules

• Fanxing Zhou,
• Chen Zhang,
• Lingyu Sun,
• Yiyun Fang,
• Siming Zheng,
• Lina Hu,
• Mengyang Shen,
• Zhen Zhao,
• Wei Xu,
• Yunqiang Sun and
• Zi-Qiang Rong

Beilstein J. Org. Chem. 2026, 22, 461–479, doi:10.3762/bjoc.22.34

• catalysis [26]. These molecules are widely found in natural products [27] and drugs, such as michellamines A and B [28], korupensamines A and B [29], diazonamide A [30], mastigophorene A [31], and the recently developed drug candidate BMS-986142 [32] (Figure 1). When a molecule contains two or more chiral

• , the medical field is actively exploring the potential applications of multiaxial chirality in drugs and therapeutics. The development of BMS-986142 [32] has further advanced treatment strategies for tumors and lymphocytic leukemia. To date, the development of bi- and multiaxial chiral architectures

Structural reassignment of compound 968, an allosteric glutaminase inhibitor

• Lindsey A. Albertelli,
• Sainabou Jallow,
• Chun Li and
• Scott M. Ulrich

Beilstein J. Org. Chem. 2026, 22, 455–460, doi:10.3762/bjoc.22.33

• glutaminase inhibition on several cancer cell lines (Figure 1) [15][16]. The anticancer effects of compound 968 have been tested in combination with other drugs such as paclitaxel [17], erlotinib [18], apigenin [19], metformin [20], and inhibitors of tissue transglutaminase [21]. Compound 968 was recently

Synthesis and anti-cancer activity of naphthalimide–organylselanyl conjugates

• Rajkumar Ravi and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2026, 22, 416–435, doi:10.3762/bjoc.22.29

• , many of which exhibit promising applications in medicinal chemistry [18][19]. Selenium has been incorporated into non-steroidal anti-inflammatory drugs (NSAIDs) and histone deacetylase (HDAC) inhibitors, both of which show considerable potential in anticancer therapy [20][21]. Over the last few decades

• anticancer drugs, such as erlotinib and gefitinib, as well as previously reported selenium- and naphthalimide-based compounds (Table 1). The comparison shows that compounds 7 and 8 have IC₅₀ values in the upper range relative to the standard drugs erlotinib and gefitinib. However, their IC₅₀ values are

Design, synthesis and biological evaluation of 2,5-diaryloxazolo[4,5-d]pyrimidin-7-ylamines as selective cytotoxic agents against HeLa cells

• Maryna V. Kachaeva,
• Agnieszka B. Olejniczak,
• Marta Denel-Bobrowska,
• Victor V. Zhirnov,
• Yevheniia S. Velihina,
• Stepan G. Pilyo and
• Volodymyr S. Brovarets

Beilstein J. Org. Chem. 2026, 22, 390–398, doi:10.3762/bjoc.22.27

• -mimicking scaffolds are a proven strategy in the design of anticancer drugs. Many cancer-related proteins (e.g., kinases, ATPases, DNA/RNA polymerases) have binding pockets designed for purine nucleotides (ATP, GTP). Oxazolopyrimidines can compete with purines or their analogues, inhibiting enzymatic

• lines represented in the corresponding NCI60 subpanel derived from leukemia, melanoma, non-small-cell lung carcinoma, and cancers of the brain, ovary, breast, colon, kidney, and prostate [13]. These results provided evidence that the compound could be helpful in developing new anticancer drugs. The

• of drug candidate development, taking into account the expected pharmacokinetic and toxicological, as well as undesirable properties of the molecules. At the same time, drug similarity filters developed by pharmaceutical companies based on the physicochemical properties of approved drugs with known

Spirobarbiturates with a pyrrolizidine moiety: synthesis, structure and biological evaluation

• Arthur A. Puzyrkov,
• Andrew S. Drachuk,
• Ekaterina A. Popova,
• Alexander V. Stepakov and
• Vitali M. Boitsov

Beilstein J. Org. Chem. 2026, 22, 274–288, doi:10.3762/bjoc.22.20

• of pharmaceutical use. Today, only slightly more than a dozen barbiturate-containing drugs remain in medical practice [4]. Nevertheless, interest in barbiturate derivatives resurged around the 1920s, when the first compounds containing a spirobarbiturate moiety were synthesized [5][6]. By the early

• using the free online software SwissADME (http://www.swissadme.ch/). The molecular descriptors were calculated according to Lipinski’s rule of five. This rule was formulated by Ch.A. Lipinski based on the observation that most orally administered drugs are relatively small and moderately lipophilic

• molecules [56]. By this rule, orally active drugs should not violate more than one of the following criteria: MW – molecular weight: < 500 Da; NHBD – number of hydrogen-bond donors, Log(P) – octanol/water partition coefficient: <5; NHBA – number of hydrogen-bond acceptors, NRotB – number of rotatable bonds

A mild and atom-efficient four-component cascade strategy for the construction of biologically relevant 4-hydroxyquinolin-2(1H)-one derivatives

• Dmitrii A. Grishin,
• Kseniia I. Sharkovskaia,
• Ilya G. Kolmakov,
• Daria A. Ipatova,
• Rostislav A. Petrov,
• Nikolai D. Dagaev,
• Dmitry A. Skvortsov,
• Maria G. Khrenova,
• Valeriy V. Andreychev,
• Sergei A. Evteev,
• Yan A. Ivanenkov,
• Roman L. Antipin,
• Olga А. Dontsova and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2026, 22, 244–256, doi:10.3762/bjoc.22.18

• cycles and enables the parallel exploration of diverse chemical space. The impact of MCRs is well documented in medicinal chemistry and pharmaceutical research, including the development of several approved drugs [14][15][16][17][18]. Recently, 4-hydroxyquinoline-2(1H)-ones and their derivatives have

Synthesis of diaryl phosphates using phytic acid as a phosphorus source

• Kazuya Asao,
• Seika Matsumoto,
• Haruka Mori,
• Riku Yoshimura,
• Takeshi Sasaki,
• Naoya Hirata,
• Yasuyuki Hayakawa and
• Shin-ichi Kawaguchi

Beilstein J. Org. Chem. 2026, 22, 213–223, doi:10.3762/bjoc.22.15

• phosphates [16]. Drugs and reagents containing phosphate ester moieties were designed as analogs of these molecules [16][17][18][19][20]. Phosphate monoesters with long aliphatic chains have also been used as surfactants [21]. Phosphate triesters are utilized as flame retardants and plasticizers for polymers

Streptoquinolines A and B, new antibacterial meroterpenoids produced by Streptomyces sp. TMPU-A0679

• Akiho Yagi,
• Hitomi Tomura,
• Ami Konno and
• Ryuji Uchida

Beilstein J. Org. Chem. 2026, 22, 185–191, doi:10.3762/bjoc.22.12

• or immunocompromised patients [2]. Current treatment relies on only a few agents, including linezolid and daptomycin, and the emergence of resistant strains to these drugs poses an additional clinical challenge [3]. Therefore, the World Health Organization (WHO) revised its Bacterial Priority

Highly electrophilic, gem- and spiro-activated trichloromethylnitrocyclopropanes: synthesis and structure

• Ilia A. Pilipenko,
• Mikhail V. Grigoriev,
• Olga Yu. Ozerova,
• Igor A. Litvinov,
• Darya V. Spiridonova,
• Aleksander V. Vasilyev and
• Sergey V. Makarenko

Beilstein J. Org. Chem. 2026, 22, 123–130, doi:10.3762/bjoc.22.5

• part of the hormaomycin antibiotic [21], and also acts as a precursor for the synthesis of the aminocyclopropane [22] moiety, which is a component of some drugs, such as ciprofloxacin [23] and belactosin A [24]. Thus, the construction of cyclopropanes containing vicinal nitro- and trichloromethyl

Total synthesis of asperdinones B, C, D, E and terezine D

• Ravi Devarajappa and
• Stephen Hanessian

Beilstein J. Org. Chem. 2025, 21, 2730–2738, doi:10.3762/bjoc.21.210

• indole alkaloids is known for its biomedical importance [2]. These alkaloids have been isolated from plants [3], marine sources [4], bacterial sources [5][6][7], and they are particularly relevant primarily because of their potent pharmacological activities as among other, anticancer drugs, but also for

Competitive cyclization of ethyl trifluoroacetoacetate and methyl ketones with 1,3-diamino-2-propanol into hydrogenated oxazolo- and pyrimido-condensed pyridones

• Svetlana O. Kushch,
• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess,
• Pavel A. Slepukhin,
• Alexandrina S. Volobueva,
• Vladimir V. Zarubaev and
• Victor I. Saloutin

Beilstein J. Org. Chem. 2025, 21, 2716–2729, doi:10.3762/bjoc.21.209

• antileishmanial [47], antibacterial [48], antimalarial agents [49] as well as COX-2 [50] and FGFR [51] inhibitors found among them. Moreover, various drugs (antipsychotic risperidone [52] and pirenperone [53], antiallergic ramastine [54]) have been obtained on the basis of pyrido[1,2-a]pyrimidine; and

Tandem hydrothiocyanation/cyclization of CF₃-iminopropargyl alcohols with NaSCN in the presence of AcOH

• Ruslan S. Shulgin,
• Ol’ga G. Volostnykh,
• Anton V. Stepanov,
• Igor’ A. Ushakov,
• Alexander V. Vashchenko and
• Olesya A. Shemyakina

Beilstein J. Org. Chem. 2025, 21, 2694–2702, doi:10.3762/bjoc.21.207

• motif in various biologically active molecules and materials due to its unique physical, chemical, and biological properties [28][29][30]. SCN and trifluoromethyl groups have proved to be versatile moieties in the design and development of numerous active pharmaceutical ingredients, agrochemicals, drugs

Synthesis of new tetra- and pentacyclic, methylenedioxy- and ethylenedioxy-substituted derivatives of the dibenzo[c,f][1,2]thiazepine ring system

• Gábor Berecz,
• András Dancsó,
• Mária Tóthné Lauritz,
• Loránd Kiss,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2645–2656, doi:10.3762/bjoc.21.205

• dibenzo[c,f][1,2]thiazepine derivatives containing a 1,3-benzodioxole or, with particular emphasis, a 1,4-benzodioxane moiety. The importance of these structural motifs is well demonstrated in medicinal chemistry by marketed drugs and by compounds that have reached the human clinical development stage in

• various therapeutic fields. Launched drugs possessing a 1,3-benzodioxole element, shown in Figure 2, are among others the cough suppressant benzylisoquinoline alkaloid noscapine [4][5], the antidepressant paroxetine [6][7], antiparkinsonian agent piribedil [8][9], and tadalafil [10][11], for the treatment

• compounds are of interest, e.g., the marketed drugs eliglustat for the treatment of Gaucher’s disease [13][14] and the antihypertensive agent proroxan [15][16]. Licogliflozin is a sodium-glucose transporter 2 inhibitor developed in several indications: obesity [17], polycystic ovary syndrome [18], and non

Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• available drugs [1]. These structures exhibit unique properties that influence pharmacokinetic and pharmacodynamic parameters, including lipophilicity, polarity, hydrogen-bonding capacity, and toxicological profiles [2][3][4]. Among them, five-membered multi-heterocyclic (FMMH) rings are privileged

• moieties exhibit a broad spectrum of biological activities [6][7][8]. They are found in several medicinal compounds (Figure 2), including etozoline (antihypertensive), ralitoline (anticonvulsant), thiazolidomycin (antibacterial), and in the type II diabetes mellitus drugs pioglitazone, epalrestat

• (GBB-3CR) [70][71][72]. These derivatives are of significant pharmacological and commercial interest, and are present in various commercial drugs, such as alpidem, miroprofen, necopidem, saripidem, zolimidine, and zolpidem [73]. Using the EDA-catalyzed Knoevenagel condensation reaction methodology

Efficient solid-phase synthesis and structural characterization of segetalins A–H, J and K

• Liangyu Liu,
• Wanqiu Lu,
• Quanping Guo and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2025, 21, 2612–2617, doi:10.3762/bjoc.21.202

• Liangyu Liu Wanqiu Lu Quanping Guo Zhaoqing Xu Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, 199 West Donggang Road, Lanzhou 730000, China 10.3762/bjoc.21.202 Abstract This study establishes an efficient solid-phase

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

• organic chemistry, and particularly in the late-stage functionalization of bioactive compounds, drugs, and natural products. This review highlights recent advances in NHC–organophotoredox dual catalysis, focusing on methodology development, mechanistic insights, and reaction scope for synthesizing

• ; NHC; organic photocatalyst; radicals; visible-light; Introduction Over the last ten years, NHC-catalyzed visible-light-promoted radical chemistry has been extensively developed for the cost-effective and practical synthesis of bioactive intermediates, pharmaceuticals, drugs, and natural products [1

• functional groups are found in various drugs, natural products, and optoelectronic materials. In the last three decades, N-heterocyclic carbenes (NHCs) have been renowned as versatile organocatalysts, including thiazolium, imidazolium, and triazolium moieties. NHCs are extensively used in many catalytic

Synthesis and characterization of a isothiouronium-calix[4]arene derivative: self-assembly and anticancer activity

• Giuseppe Granata,
• Loredana Ferreri,
• Claudia Giovanna Leotta,
• Giovanni Mario Pitari and
• Grazia Maria Letizia Consoli

Beilstein J. Org. Chem. 2025, 21, 2535–2541, doi:10.3762/bjoc.21.195

• promising candidates for further investigations as a drug delivery system. The entrapment of different drugs combined with the intrinsic anticancer activity of the nanoassemblies could provide new agents for a combination multidrug anticancer treatment. Experimental Materials and methods: All chemicals were

Catalytic enantioselective synthesis of selenium-containing atropisomers via C–Se bond formations

• Qi-Sen Gao,
• Zheng-Wei Wei and
• Zhi-Min Chen

Beilstein J. Org. Chem. 2025, 21, 2447–2455, doi:10.3762/bjoc.21.186

• Qi-Sen Gao Zheng-Wei Wei Zhi-Min Chen State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Shanghai Jiao Tong University, Shanghai 200240, P. R. China 10.3762/bjoc.21.186 Abstract

Insoluble methylene-bridged glycoluril dimers as sequestrants for dyes

• Suvenika Perera,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 2302–2314, doi:10.3762/bjoc.21.176

• minerals, cleaning products, personal care products, plastics, fertilizers, and lifesaving medicines along with deleterious substances including drugs of abuse and environmental toxins. For deleterious substances that enter the human body, in vivo antidotes are required. For example, naloxone is a well

• functionalized and can flex their methylene-bridged glycoluril oligomer to accommodate guests of different size. Water-soluble acyclic CB[n] have been used as in vivo sequestrants for drugs of abuse, neuromuscular blockers, and anesthetics and as solubilizing agents for pharmaceuticals [31][32][33][34][35][36

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• intermediate in synthesis [1][2]. Several nucleoside analogue drugs are prepared using γ-butyrolactones, that when reduced give pentose sugars that can be used as glycosyl donors [3][4]. A number of these clinically used drugs contain fluorine as a hydroxy bioisostere at C2, most notably gemcitabine (1) and

Research towards selective inhibition of the CLK3 kinase

• Vinay Kumar Singh,
• Frédéric Justaud,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Blandine Baratte,
• Thomas Robert,
• Stéphane Bach,
• Chada Raji Reddy,
• Nicolas Levoin and
• René L. Grée

Beilstein J. Org. Chem. 2025, 21, 2250–2259, doi:10.3762/bjoc.21.172

• kinases have become one of the most important drug targets: between a quarter to a third of the drug discovery efforts worldwide are focused on the discovery of new protein kinase inhibitors. More than 80 FDA-approved drugs that target about two dozen different protein kinases were discovered during the

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

• phenylhydrazone structural unit is present in several marketed drugs (herombopag [28], eltrombopag [29], levosimendan [30]) and in drug candidates that reached the human clinical trials (totrombopag [31], FP-21399 [32], sivifene [33]), hydrazone intermediates 7a–j and (E)-9a,b were also involved in the tests. The

• Table 3. The preliminary ADME investigation, characterized by first-order kinetics due to low substrate concentration (≤10 µM), aids in establishing intrinsic clearance (Clint), which indicates the predicted elimination efficacy of drugs [43]. According to the generally accepted Clint ≈ 10 μL/min/kg (or

Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design

• Daniil V. Khabarov,
• Valeria A. Litvinova,
• Lyubov G. Dezhenkova,
• Dmitry N. Kaluzhny,
• Alexander S. Tikhomirov and
• Andrey E. Shchekotikhin

Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161

• systems, exhibiting a wide range of biological activity, high level of druglikeness and broad opportunities for derivatizations, that make them privileged scaffolds in drug discovery [2][3]. The pharmaceutical significance of indole and quinazoline rings is evident by numerous FDA-approved drugs across

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