Electrochemical reduction of unsaturated carbon–carbon bonds via 3d transition-metal catalysis

• Geon Kang,
• Minki Jeon,
• Pooja Kumari Jat,
• Cheoljae Kim and
• Isaac Choi

Beilstein J. Org. Chem. 2026, 22, 955–981, doi:10.3762/bjoc.22.75

• exhibiting co-catalytic behavior through direct interaction with the reaction intermediate, from which protonation releases the final product while regenerating the active mediator. Collectively, these observations support the operation of an ECEC-type pathway and provide strong mechanistic evidence that

Recent advances in copper-catalyzed direct hydroamination of alkenes with (hetero)aromatic amines

• Hyejeong Lee and
• Yunmi Lee

Beilstein J. Org. Chem. 2026, 22, 925–947, doi:10.3762/bjoc.22.73

• is because the direct interaction between an electron-rich nitrogen lone pair and a relatively inert alkene π-system is often kinetically disfavored in the absence of activation [19]. Furthermore, the hydroamination of unsymmetrical alkenes introduces additional complexity in controlling the

Chiral cyclopropenimine-catalyzed enantioselective Michael reactions of phenol and benzofuran-derived α,β-unsaturated pyrazolamides with benzophenone-imine of glycine esters

• Ya Bai,
• Xue-Ying Wang,
• Si-Kai Zhu,
• Yan-Ting Shen,
• Sheng-Yong Zhang and
• Ping-An Wang

Beilstein J. Org. Chem. 2026, 22, 888–896, doi:10.3762/bjoc.22.69

• stereospecific ability of CSB-1. This may be due to a more flexible hydrogen-bonding donor group and a smaller steric hinderance in CSB-1 than in other cyclopropenimines to provide good hydrogen-bonding interaction in the transition state [13]. With decreasing amount of CSB-1 from 20 mol % to 10 mol %, the yield

• ion pair A, which attacks β-substituted α,β-unsaturated pyrazolamide 5a to provide transition state B. Transition state B may be stabilized through an H-bonding interaction network between the two substrates and CSB-1. Additionally, π–π stacking between the two phenyl groups of 2a and 5a may also

Diastereodivergent electrophilic trapping of α-boryl lithium derivatives

• Tereza Pavlíčková,
• Noam Orbach and
• Ilan Marek

Beilstein J. Org. Chem. 2026, 22, 882–887, doi:10.3762/bjoc.22.68

• revealed that the electrophile preferentially approaches from the face opposite the coordinating lithium cation, with the lowest-energy transition state stabilized by a lithium cation–vinyl interaction (see A in Scheme 1) [34]. Results and Discussion The intricate interplay of the coordination and steric

Site-specific labelling of native peptides and proteins: chemical and enzymatic strategies

• Antonio Angelastro,
• Jonathan Bargh,
• Subhajit Guria,
• Victor Laserna and
• Louis Luk

Beilstein J. Org. Chem. 2026, 22, 857–881, doi:10.3762/bjoc.22.67

• has been the development of linchpin-directed modification (LDM) [104]. These bifunctional reagents contain two reactive groups separated by a spacer: one engages in a reversible interaction with a common surface residue, while the other is an irreversible chemical handle that covalently modifies a

• arginine by reagents carrying a) glyoxal 27, b) phenanthrenequinones 28, c) DKPA 29 groups and d) methylglyoxal (30). Examples of linchpin-directed modification targeting a) histidine, b) aspartic acid, and c) lysine residues via transient interaction with neighbouring residues, including lysine-reacting o

Knoevenagel condensation of 4,5- and 1,8-diazafluorenes

• Darya S. Cheshkina,
• Christina S. Becker,
• Alina A. Sonina and
• Maxim S. Kazantsev

Beilstein J. Org. Chem. 2026, 22, 803–812, doi:10.3762/bjoc.22.62

• . Specifically, solvation by aprotic DMF having a high dipole moment promotes the formation of the [Na+–diazafluorenyl−] ion pair, whose anion displays insufficient nucleophilicity for interaction with weakly electrophilic aldehydes (e.g., benzaldehyde and 4-methoxybenzaldehyde). On the other hand, tert-butanol

Design, synthesis, and biological evaluation of FXR/ASK1 dual-target modulators

• Xi Zhang,
• Jingyan Wang,
• Ziqiang Zhao,
• Caiyi Wang,
• Zenghui Ye,
• Wei-Yuan Ma,
• Jian-Xing Xu and
• Fengzhi Zhang

Beilstein J. Org. Chem. 2026, 22, 771–781, doi:10.3762/bjoc.22.59

• -aliphatically substituted 4H-1,2,4-triazolopyridine biaryl scaffold of selonsertib [31][39][40], as key pharmacophores. In the co-crystal structure of hFXR-LBD with GW4064 [41], the isoxazole core coordinates the π-cation interaction between His 447 and Trp 469; the 5-isopropyl group is embedded into a

• hydrophobic pocket formed by Phe 284, Leu 287, Trp 454, and Phe 461; the dichlorophenyl moiety engages in π–π stacking with Phe 329; and the meta-positioned carboxy group forms a strong electrostatic interaction with Arg 331. The modification strategies for GW4064 are as follows: The stilbene moiety can be

Synthesis and biological evaluation of new brassinosteroid analogs with C-22 benzoate function

• María Núñez,
• Camila Escobar,
• Mario Párraga,
• Mauricio Soto,
• Luis Espinoza-Catalán,
• Katy Díaz and
• Andrés F. Olea

Beilstein J. Org. Chem. 2026, 22, 753–762, doi:10.3762/bjoc.22.57

• . Keywords: biological activity; brassinosteroids; BRI1-EMS-Suppressor1; ligand–receptor interaction; structure–activity relationship; Introduction Brassinosteroids (BRs) are phytohormones that are widespread in the plant kingdom, and are found in very low concentrations, i.e., in the of nano- to micromolar

• data suggest that the initial step of the signaling process and the subsequent dephosphorylation of BES1 depend on the structure of BRs analogs in the same way. In other words, the interaction between BRs analogs and the binding site determines the response of the plant and one intermediate step

• , conjugation and oxidation via dynamic interaction with different phytohormones and on homeostasis mechanisms [52]. Consequently, exogenous application of a growth regulator initiates not only the process leading to a phenotypic response but also all those associated to its own regulation. Thus, only a

Rongalite addition to dienones: diastereoselectivity in cyclic sulfone synthesis; stereochemical rationalization and prospects as a general conjugate nucleophile

• Melina Goga,
• Hao Zong,
• James Franco,
• Jazmine Prana,
• Rudolph Michel,
• Antonia Muro,
• Elana Rubin,
• Janet Brenya,
• Henk Eshuis and
• Magnus W. P. Bebbington

Beilstein J. Org. Chem. 2026, 22, 742–752, doi:10.3762/bjoc.22.56

• bonds in TS-trans, there is a significant distortion in the chair shape in TS-cis: the two highlighted CH bonds are not parallel – they are converging and this 1,3-diaxial interaction may be a contributing factor in increasing the activation barrier relative to TS-trans. Further technical discussion of

Synthesis of heterocycles based on azomethine ylides from α-amino acids (or amines) and carbonyl compounds

• Ekaterina V. Berezhnaya,
• Alexander I. Ponyaev,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2026, 22, 705–741, doi:10.3762/bjoc.22.55

• , the importance of the formation of azomethine ylides from amino esters, amino acids, imine derivatives, aziridines or other substrates was emphasized. A review [26] demonstrates metal-catalyzed as well as metal-free asymmetric and racemic transformations of imino ethers upon interaction with various

• absence of interaction between the metal and the electron-withdrawing group of the dipolarophile, and the coordination properties of the metal, for example, the possibility of changing the coordination sphere of copper(I) from bidentate to monodentate, which does not occur with the Ag(I) atom, which has

• containing cyclic succinimide, pyrrolidine, pyrrolizidine, and chroman moieties [73] (Scheme 30). The authors showed that the first stage involves intermolecular 1,3-dipolar cycloaddition of azomethine ylides obtained as a result of the interaction of aromatic aldehydes 67 and glycine methyl ester (62) to N

Using generative AI to transform peptide hits into small molecule leads

• Joshua Mills and
• Yu Heng Lau

Beilstein J. Org. Chem. 2026, 22, 672–679, doi:10.3762/bjoc.22.51

• protein–ligand dataset (from Binding MOAD [51]) to factor in the constraints of typical binding pockets. ShEPhERD is an interaction-aware diffusion model developed by Coley and co-workers that is capable of bioisosteric fragment merging [39]. For fragment merging, the model was trained on a subset from

Photoorganocatalytic trifluoromethylation of (het)arenes in green conditions

• Egor N. Boronin,
• Svetlana E. Kaurkina,
• Milena M. Svetlakova,
• Anton S. Bolshakov,
• Maxim V. Arsenyev,
• Vasilii F. Otvagin,
• Alexey Yu. Fedorov,
• Timothy Noël and
• Alexander V. Nyuchev

Beilstein J. Org. Chem. 2026, 22, 662–671, doi:10.3762/bjoc.22.50

• excited state by both TFAA and TMB revealed very similar quenching constants: Kq(TFAA) = 6.07 × 109 M−1·s−1 and Kq(TMB) = 5.37 × 109 M−1·s−1 (Figure S16; for further details, see Supporting Information File 1). These results indicate that either initial interaction is feasible under the reaction

Advantages of PROTACs in achieving selective degradation of homologous protein families

• Luxi Yang,
• Xinfei Mao,
• Jingyi Zhang,
• Jing Shu,
• Wenhai Huang,
• Xiaowu Dong,
• Yinqiao Chen and
• Mingfei Wu

Beilstein J. Org. Chem. 2026, 22, 628–661, doi:10.3762/bjoc.22.49

• ; PROTAC; protein–protein interaction; selectivity; ubiquitination; Introduction The cell is the fundamental unit of structure and function in the human body [1][2]. More than 20,000 proteins act in concert to regulate the entire cellular life process [1]. To date, dysregulated protein function has been

• other non-enzymatic proteins [7] are essentially undruggable using conventional inhibitor-based approaches [4][8]. Consequently, protein–protein interaction (PPI)-based targeted protein degradation (TPD) strategies have attracted increasing attention over the past two decades [9][10]. Among them

• . NanoBRET and ITC experiments indicated that compound 37 induces a stable protein–protein interaction interface between BRD4BD2 and VHL through linker-mediated conformational locking, achieving a cooperativity factor (α) of 117, which is significantly higher than those of compounds 35 and 36. Its co-crystal

Continuous-flow carbonyl hydrogenation under subatmospheric to atmospheric hydrogen pressure enabled by robust heterogeneous Pt–Fe catalysts

• Hiroyuki Miyamura,
• Ryosuke Kajiyama,
• Shun-ya Onozawa,
• Yoshihiro Kon and
• Shū Kobayashi

Beilstein J. Org. Chem. 2026, 22, 575–582, doi:10.3762/bjoc.22.43

• best among the solvents tested (EtOAc, toluene, methylcyclohexane, tetrahydrofuran, and methanol) (see Supporting Information File 1, Figure S5). The hydroxy moiety has a stronger interaction with catalytically active sites at the surface of the heterogeneous catalyst, and smooth desorption of the

Kinetic resolution of racemic planar-chiral vinylcymantrenes by molybdenum-catalyzed asymmetric metathesis dimerization

• Haruna Imazu,
• Hitoshi Izu,
• Yasuhiro Ohki and
• Masamichi Ogasawara

Beilstein J. Org. Chem. 2026, 22, 568–574, doi:10.3762/bjoc.22.42

• in Figure 2) likely inhibits the effective interaction of the substrate with the chiral catalyst, resulting in highly enantioselective kinetic resolution. Cymantrene is far less electron-poor than ferrocene due to the presence of the three carbonyl ligands, which are strong π-acids, on the manganese

Molecular tweezer–peptide conjugates disrupt the protein–protein interaction between survivin and histone H3 essential in mitosis

• Catherine Gsell,
• Philipp Rebmann,
• Karina Opara,
• Christine Beuck,
• Peter Bayer,
• David Bier,
• Ingrid R. Vetter and
• Thomas Schrader

Beilstein J. Org. Chem. 2026, 22, 557–567, doi:10.3762/bjoc.22.41

• , Otto-Hahn-Straße 11, 44227 Dortmund, Germany 10.3762/bjoc.22.41 Abstract Peptide-modified supramolecular tweezers, a promising new class of chemical tools, were designed and employed to inhibit the interaction of the BIR domain of human survivin, a member of the chromosomal passenger complex (CPC

• ; protein–protein interaction; mitosis; X-ray crystallography; Introduction The fundamental process of mitosis is controlled by a very large protein complex called the kinetochore, formed by self-assembly from hundreds of single protein components [1]. For the intricate regulation of the various phases of

• bound tightly to each other by aligning their extended α-helices (Figure 1) [5]. Intriguingly, CPC recruitment hinges on a few very distinct protein contacts, involving borealin and the BIR domain of survivin. A very dominant protein–protein interaction (PPI) is the embedding of the N-terminus of

Experimental and DFT studies on the regioselective methanolysis of 5-azido-9-oxabicyclo[6.1.0]nonan-4-yl 4-nitrobenzoate isomers

• İlknur Polat,
• Selçuk Eşsiz and
• Emine Salamci

Beilstein J. Org. Chem. 2026, 22, 547–556, doi:10.3762/bjoc.22.40

• correlates well with the computed activation barriers and the divergence of the competing reaction pathways. In this context, despite the presence of a hydrogen-bonding interaction in TS2, TS1 is lower in energy due to a more favourable cyclooctane conformation. Notably, the relatively small energy

Melifoliox B, a novel phloroglucin derivative isolated from Melicope barbigera (Rutaceae) and synthesis of new oxidation products from melifoliones A and B

• Horst Weber,
• Kim-Thao Tran-Cong,
• Bernhard Mayer,
• Guido J. Reiss,
• Iryna S. Konovalova,
• Marc S. Appelhans,
• Kenneth R. Wood and
• Claus M. Passreiter

Beilstein J. Org. Chem. 2026, 22, 535–546, doi:10.3762/bjoc.22.39

• , a cross peak was found for the interaction of C-3’ with the protons of the 6-CH3 group. These observations suggest unusual (4J)-long-range C/H-couplings in the rigid spirocyclic 4-ring system. The formation of 11 can be suggested by the following hypothetical pathway (Scheme 3): In a first step, the

Synthesis of a HDAC inhibitor–nanogold probe for cryo-EM visualization in class I HDAC co-repressor complexes

• Wiktoria A. Pytel,
• John W. R. Schwabe and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2026, 22, 480–485, doi:10.3762/bjoc.22.35

• -complete inhibition of the HDAC activity in the CoREST complex, even at 0.54 μM. Surprisingly, Au–NH2 was found to reduce the HDAC activity of the CoREST complex by nearly 50%. One plausible explanation for this effect is a direct interaction between the gold nanoparticles and solvent-accessible cysteine

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

• cancer cell line. Molecular docking simulation revealed strong binding interaction and affinities towards the tyrosine kinase domain of epidermal growth factor receptor (EGFR), and the protein–ligand interaction resembles the interaction found in the co-crystallised protein–erlotinib complex. Result and

• geometry around the selenium atom. The structure reveals the four distinct intermolecular interactions that facilitate the self-assembly in the crystal packing. The first is a chalcogen bonding interaction (Se···Se) [53], as shown in Figure 2b, in which one aryl selenide molecule linearly connects to

• another, with a Se···Se distance of 3.703 Å. The second is a selenium–carbon (Se···C) interaction as shown in Figure 2c, where the molecules are arranged in a top-down orientation [54]. In this orientation, the Se motif of one molecule interacts with the carbonyl carbon of another molecule, showing the Se

Cone p-aminocalix[4]arenes enriched with ‘clickable’ alkyne or azide functionalities

• Ilia Korniltsev,
• Vasily Bazhenov,
• Alexander Gorbunov,
• Dmitry Cheshkov,
• Stanislav Bezzubov,
• Vladimir Kovalev and
• Ivan Vatsouro

Beilstein J. Org. Chem. 2026, 22, 399–415, doi:10.3762/bjoc.22.28

• /receptor units, thus drastically improving their supramolecular interaction capabilities. This property of p-aminocalix[4]arenes has been widely utilized in constructing f-element-targeted extractants for nuclear waste treatment, having four carbamoylmethylphosphine oxide groups introduced to the

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

• supported by virtual assay results indicating low human toxicity, low probability of interaction with receptors in the Tox21 pathways, very weak substrate specificity for Pgp, very low likelihood of oxidative metabolism, and inability of compound 9 to cross the blood–brain barrier. Hence, according to the

• compounds 1, 7, and 9 determine the threshold values of BBB permeability according to the CNS rule descriptor. Predicted parameters of human toxicity of compounds 1, 7, and 9. Predicted probability of interaction of compound 1, 7, and 9 with nuclear receptor (NR) signaling, and stress response (SR) pathways

Recent advances in the cleavage of non-activated amides

• Eun-Sol Choi and
• Hyo-Jun Lee

Beilstein J. Org. Chem. 2026, 22, 352–369, doi:10.3762/bjoc.22.23

• bromine (Br2), which converts the amide into N-bromobenzamide. Meanwhile, at the cathode, the alcohol is partially deprotonated to form an alkoxide, which engages in a stabilizing hydrogen-bonding interaction to produce the acid–base pair V. Nucleophilic attack of V on N-bromobenzamide forms a tetrahedral

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

• results obtained, docking simulations were performed for the possible interaction of spiro-adducts with actin, as the most widespread and highly conserved cellular protein. Since the initial determination of the G-actin crystal structure in complex with DNase I, many actin structures have been registered

Arene activation via π-bond localization: concepts and opportunities

• Paul Meiners,
• Julian J. Melder and
• Tobias Morack

Beilstein J. Org. Chem. 2026, 22, 257–273, doi:10.3762/bjoc.22.19

• complexes rests on a finely balanced synergistic interaction: the metal center accepts electron density from a filled π orbital of the arene while engaging in π-backbonding, donating electron-density into an empty π* orbital (Figure 4A) [43]. This interaction not only stabilizes the metal–arene bond but

• of the archetypal pentaammineosmium(II) system prior to discussing synthetic utility (Figure 6). The five ammine ligands, strong σ-donors with negligible π-interaction, combined with the d6 configuration render the Os(II) center highly electron-rich and an exceptional π-base [43]. This electronic

•  6B) [45]. Application in organic synthesis Organic transformations of η2-coordinated arenes can be broadly divided into three categories, depending on what dictates reactivity: the polarization of the free molecule, the site of metal coordination, or the backbonding interaction itself. Early studies