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

• , 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

• normal fibroblasts (HSF) compared to cancer cells, the differences were moderate (less than twofold). These results suggest a modest preferential cytotoxicity toward cancer cells, particularly in the case of compound 2 against MCF7, though further studies are needed to establish meaningful selectivity

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• -workers. In two separate reports, they synthesized well-defined MOFs composed of three different linkers: a proline-functionalized linker acted as the catalytic unit, while two auxiliary linkers were varied to alter catalyst activity and enantioselectivity [24], or product selectivity [25]. In those works

• pharmaceutical and agrochemical industries [38][39]. Various types of catalysts are used to enhance the efficiency and selectivity of the Knoevenagel reaction, including Lewis acids, ureas/ thioureas, amino acids, and bases such as alkali metal hydroxides, alkali metal alkoxide, amines, etc. [37][40][41][42][43

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

• , FeCl3·6H2O provided the best results (Table 1, entry 2). A further reduction in catalyst loading from 25 mol % to 20 mol % and 10 mol % resulted in a noticeable decrease in both selectivity and conversion efficiency (Table 1, entries 7 and 8). This is likely due to insufficient C(sp2)–C(sp2) bond

• considerably reduced both the conversion and selectivity (Table 1, entry 14). Furthermore, when K2S2O8 was used as the oxidizing agent instead of O2, a considerable drop in both conversion and selectivity was observed. Having identified satisfactory conditions, we sought to examine the scope and generality of

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

• 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

• -step synthesis, convenient modification that can be achieved by introducing functional groups, electron rich and hydrophobic cavities that can effectively recognize electron deficient or neutral guest molecules, and high selectivity in binding with the guest. Their applications are extensive in the

• molecules and high-selectivity binding in drug-controlled release. Many calix/pillar[n]arene hosts are soluble in water, particularly macrocycles that are modified with carboxyl and phosphate groups. Moreover, their amphiphilic modification ability allows easy self-assembly into functional materials like

Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• to form a tert-butyl ester, leading to unwanted side products and reduced selectivity. Once the acid was protected, the Boc group could be selectively introduced onto the indole nitrogen without side reactions. Overall, this sequence ensured clean N-Boc protection with minimal side reactions and

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• precursors [38][39][40][41][42]. This emphasizes the importance of reliable and reproducible approaches for the stereoselective synthesis of unsymmetrically orthogonally protected nonreducing disaccharides. While the desired anomeric selectivity on the side of the glycosyl donor can often be achieved by

• were readily prepared by self-condensation of the corresponding acetylated methyl 1,2-orthoacetates using BF3·OEt2 as a promoter [55]. While the 1,2-orthoester functionality in the glycosyl donor 17 directed the 1,2-trans selectivity towards the formation of an α-mannosidic linkage, the anomeric β

• selectivity in glycosylations with various types of nucleophiles [67][68]. This remarkable stereoselectivity has been attributed to intermolecular hydrogen bonding, which forms a transient tether between the glycosyl donor and acceptor, thereby guiding the reaction towards a preferred stereochemical outcome

Continuous-flow-enabled intensification in nitration processes: a review of technological developments and practical applications over the past decade

• Feng Zhou,
• Chuansong Duanmu,
• Yanxing Li,
• Jin Li,
• Haiqing Xu,
• Pan Wang and
• Kai Zhu

Beilstein J. Org. Chem. 2025, 21, 1678–1699, doi:10.3762/bjoc.21.132

• /selectivity through optimized parameters (microwave energy, temperature, feed composition) [11]. Recent years have witnessed growing adoption of the continuous-flow technology in nitration processes across laboratory and industrial scales, driven by the reaction's classification as a highly hazardous chemical

• -flow nitration innovatively reimagines conventional methods for managing exothermic and selectivity-sensitive reactions, systematically analyzing four distinct approaches (nitration with mixed acids; nitration with fuming nitric acid; vapor-phase nitration; nitration with solid acid catalysts) to

• regioselectivity and product purity. Nitrating reagents: Nitrating reagents play a pivotal role in determining the efficiency, selectivity, and safety of nitration processes, with their selection being fundamentally dependent on the nature of the substrate and desired reaction outcomes. Analytical data (Figure 4a

Structural analysis of stereoselective galactose pyruvylation toward the synthesis of bacterial capsular polysaccharides

• Tsun-Yi Chiang,
• Mei-Huei Lin,
• Chun-Wei Chang,
• Jinq-Chyi Lee and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2025, 21, 1671–1677, doi:10.3762/bjoc.21.131

• position. Additionally, THF was used as a solvent to enhance the α-selectivity of the reaction [41][42][43]. Next, while both compounds 8 and 9 can act as acceptors, compound 9, a primary alcohol, exhibits greater nucleophilicity. Using the TolSCl/AgOTf promoter system at −70 °C, the β-linked disaccharide

• 10 was formed, giving 71% yield (α/β = 1:6). According to the RRV/Aka platform [44], compound 9 is a robust nucleophile, with an Aka value of 12 [45]. This high nucleophilicity favors a SN2-like mechanism, promoting β-selectivity [46]. Using the difference in acceptor reactivity and activation method

• β-selectivity due to the neighboring group effect [41][48][49][50]. Subsequently, treatment with triethylsilane (Et₃SiH) and trimethylsilyl trifluoromethanesulfonate (TMSOTf) led to the opening of the benzylidene ring and removal of the TMS group, yielding compound 14, which can serve as an acceptor

Formal synthesis of a selective estrogen receptor modulator with tetrahydrofluorenone structure using [3 + 2 + 1] cycloaddition of yne-vinylcyclopropanes and CO

• Jing Zhang,
• Guanyu Zhang,
• Hongxi Bai and
• Zhi-Xiang Yu

Beilstein J. Org. Chem. 2025, 21, 1639–1644, doi:10.3762/bjoc.21.127

• have 75-fold selectivity of ERβ over Erα [12]. Molecules III and IV (Scheme 1A) with an additional pyrazole ring compared to I and II had good pharmacokinetic properties that had overcome the problems of rapid clearance and low oral bioavailability executed by previous molecules [13][14]. A series of

• bridged tetrahydrofluorenone derivatives, represented by molecules V and VI, showed significant ERβ binding affinity and high selectivity [15][16][17][18][19]. So far, there are only two routes for accessing bridged tetrahydrofluorenone derivative VI. The first one shown in Scheme 2A includes a Robinson

On the aromaticity and photophysics of 1-arylbenzo[a]imidazo[5,1,2-cd]indolizines as bicolor fluorescent molecules for barium tagging in the study of double-beta decay of ¹³⁶Xe

• Eric Iván Velazco-Cabral,
• Fernando Auria-Luna,
• Juan Molina-Canteras,
• Miguel A. Vázquez,
• Iván Rivilla and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2025, 21, 1627–1638, doi:10.3762/bjoc.21.126

• efficiency of crown ethers as components in cation-selective fluorescent probes has been extensively explored [7][30], to the best of our knowledge no previous computational DFT studies on the selectivity of crown ethers of different sizes with Ba2+ have been reported. Therefore, we explored (Scheme 2A) the

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• reaction carried out in the presence of 5 mol % of NiSO4 gave not only dimer 4, but also the annulation product, compound 3a. Further optimization of the reaction conditions aimed at suppressing the formation of dimer 4 showed that nickel chelates exhibit enhanced selectivity in catalyzing the annulation

• -catalyzed reaction proceeds with low diastereoselectivity. The significant difference in selectivity can be explained by the fact that, in contrast to the Ni(II)-catalyzed reaction depicted in Scheme 3, the copper(I) catalysis involves the coordination by the metal of both reaction partners, and the

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

• -bromochromones via a Michael reaction of an amine with an electron-deficient alkene moiety and subsequent photocatalyzed debromination. With this dual catalytic system, a range of structurally diverse enaminone derivatives have been achieved in good yields with total trans selectivity. Mechanistic studies

Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Marcin Palusiak,
• Heinz Heimgartner,
• Marta Denel-Bobrowska and
• Agnieszka B. Olejniczak

Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113

• selectivity, and in all cases formation of insertion products of both types, i. e., thioaminals 9 and dithioacetales 10, was observed (see Table 1). Chromatographic separation enabled the isolation of pure compounds, and the more stable dithioacetals 10 formed the more polar fraction. The less polar fraction

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

• diaryliodonium salts under photoredox conditions has been proposed for the first time. The suggested procedure allows preparing a broad range of benzamides using both symmetric and unsymmetric diaryliodonium salts under mild conditions. A plausible mechanism for the reaction and the selectivity of aryl transfer

• for unsymmetrical iodonium salts. Therefore, we moved to these to test the selectivity of aryl transfer under the established conditions. Since iodonium salts are prone to repeat the selectivity pattern of nucleophilic substitution in photoredox processes [35][36][37][38][39][40][41], we evaluated

• iodonium salts with common dummy ligands such as 2,4,6-trimethoxyphenyl (TMP) [42][43], sterically hindered 2,4,6-triisopropylphenyl, and mesityl ligands. The highest selectivity was achieved using aryl(2,4,6-trimethoxyphenyl)iodonium triflates 1n–p yielding the desired amides 2ba, 2bo, and 2bp in 25–42

Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper

• Andrei Paraschiv,
• Valentina Maruzzo,
• Filippo Pettazzi,
• Stefano Magliocco,
• Paolo Inaudi,
• Daria Brambilla,
• Gloria Berlier,
• Giancarlo Cravotto and
• Katia Martina

Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108

• demonstrated good product conversion and selectivity without the need to perform the reaction under oxygen, while Cu(OAc)2 was slightly less efficient. When the catalyst loading was reduced to 15 mol %, the reaction yield decreased to approximately 75% for both copper salts. However, reducing the reaction time

• to 6 hours, with a catalyst loading of 20 mol %, resulted in complete conversion and high selectivity, comparable to the results obtained from an overnight reaction. Notably, decreasing the reaction temperature to 60 °C still yielded excellent results with both catalysts after an overnight reaction

• reported in numerous green protocols, offer significant advantages over the use of conventional heating. The goal was to utilise selective, volumetric dielectric heating to save time and energy, enable selective catalysis and generally achieve higher selectivity and yields [53][55][56]. Building on the

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

• infants and it has successfully completed a phase III clinical trial [17][18]. Finally, sulphonamide 4 is a lead compound for the treatment of osteoarthritis via MMP-13 (matrix metalloproteinase 13) inhibition which exhibited an excellent selectivity profile and complete inhibition of collagenolysis in

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• transfer (HAT) in photocatalytic reactions. These radicals display exceptional selectivity and efficiency in abstracting hydrogen atoms from C–H, Si–H, B–H, and Ge–H, positioning them as invaluable tools in synthetic chemistry. This review summarizes the latest advancements in the photocatalyzed generation

• /mol (Figure 2a) [28][29][30]. Almost 5 kcal/mol difference between two species could spontaneously undergo a HAT process. That also justifies the selectivity and efficiency of amidyl radical serving as HAT reagent. 2) Recent research indicated a critical correlation between electronic effects and

• a central role in this photocatalytic system. This strategy demonstrated good chemical selectivity for the functionalization of pyridine and alkanes, resulting in 55% to 86% yields of products 38, 39, 40, and 41, respectively. Amidyl radical from N–O bond cleavage In 2022, Alexanian’s group

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• oxidation: The Scholl-type oxidation has also been employed also for azulene-embedded PAHs. where it was used to fuse substituents around the already existing azulene moiety in the direct precursor. However, such reactions often lead to suboptimal results in terms of yield and selectivity. Positions 1 and 3

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

• ) [6]. This methodology enabled the selective functionalization of one or two C(sp3)–H bonds adjacent to the nitrile group, leading to the formation of diverse polycycles with high selectivity. Various reaction parameters were systematically examined, including Lewis acids, oxidants, bases, reaction

• selectivity, and high functional group compatibility (65a–f). In 2024, Huang, Liu, and Li’s group introduced a novel approach for the photochemical radical cascade 6-endo cyclization of dienes using α-carbonyl bromides, as illustrated in Scheme 32 [20]. This method is characterized by a visible-light-induced

Selective monoformylation of naphthalene-fused propellanes for methylene-alternating copolymers

• Kenichi Kato,
• Tatsuki Hiroi,
• Seina Okada,
• Shunsuke Ohtani and
• Tomoki Ogoshi

Beilstein J. Org. Chem. 2025, 21, 1183–1191, doi:10.3762/bjoc.21.95

• well with the observed reactivities and selectivity. Attempted macrocyclization leading to linear polymers Formyl groups have diverse reactivities and enable facile condensation, dynamic covalent chemistry, and so on. In this work, we tried the synthesis of cyclic oligomers composed of naphthalene

• N2 adsorption and desorption. Molecular design for uniform microporosity and efficient polymerization is a next challenge. Conclusion In this work, we developed formylation on a naphthalene ring in [3.3.3]- and [4.3.3]-type fully π-fused propellanes. High selectivity was achieved for monoformylation

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

• the Z-product during the cross-metathesis reactions. Therefore, the synthetic study was initiated by performing cross-metathesis reactions between both (E,E)- and (Z,E)-134 with various alkenes to investigate the Z- or E-selectivity of the reaction. Fortunately, Iqbal observed that all cross

• -metathesis reactions in the study exhibited high E-selectivity. As a result, the reaction of (Z,E)-134 with olefin 135 provided the desired product 136 in 56% yield, with a (Z,E)/(Z,Z) ratio of 4:1 (Scheme 21). Compound 136 was subsequently protected as a TBS ether, 137 [35]. The aldehyde counterpart 147 for

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

• compound selectivity was made using the human embryonic kidney cell line HEK293, according to previously reported protocols [16][17]. The results are shown in Table 1, including IC50 values for the reference compounds puromycin, chloroquine, pyrimethamine, and dihydroartemisinin. Compounds 2–9 and 15 did

• limited activity against Pf 3D7 resulted in low selectivity indices, as indicated in Table 1. Compounds 3 and 13–15 demonstrated some inhibition of HEK293 at the highest concentrated tested, but did not display sigmoidal dose-dependent kinetics, thus accurate IC50 values were unable to be determined

• . Meaningful selectivity indices for these compounds could, therefore, likewise not be calculated. Hence, the mean % growth inhibition (duplicate, n = 1) at the top concentration is indicated in Table 1. Conclusion A modified approach for amine substitution of 5-chloro-3-(4-chlorophenyl)-[1,2,4]triazolo[4,3-a

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

• high selectivity. The present review is centered on the use of cyclodextrins, natural and biocompatible oligosaccharides that form upon microbial fermentation of starch. The method is environmentally safe because it resorts to natural compounds, posing as a promising alternative to the use of cyanides

• such as sodium sulfite. As a disadvantage, the step of gold reduction causes co-precipitation of all other metals that are present in solution, which has raised the need for the use of selective precipitation methods. One of the strategies to address this selectivity precipitation issue is the use of β

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• kinetically controlled diastereofacial selectivity. The resulting diastereomers are separable by chromatography. 1H NMR was used to assign the configuration of the 2 diastereomers [53][54][55]. Carbon C2 is R-configured, as ᴅ-2-aminoadipic acid (1) was employed as the starting material. The minor diastereomer

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• -branched (L/B) selectivity of >20:1. The reaction involves the formation of palladium hydride (Pd–H) 270 as the key species followed by alkyne and CO insertion reactions via 271 and 272 (Scheme 68A) [116]. On the one hand, Jia and co-workers (2021) utilized environmentally benign water as the hydrogen

• -Markovnikov selectivity catalyzed by Au(III) in the presence of dimethylaminopyridine N-oxide (DMAPO) as oxidant. The reaction proceeds via Au–allenylidene species 307 (Scheme 73) [124]. Various cinnamic esters and amides with natural product-based alkoxy groups 301–304 and sulfoximines 305 and 306, a

• cinnamamides 13, 77, 99, and 371 in good yields via the active palladium–hydride species 372 (Scheme 81A) [137]. The Z-to-E-selectivity could be effectively tuned by changing the solvent and temperature from CH3CN to DMF and rt to 80 °C, respectively. Similarly, Wang and co-workers (2023) employed Pd to