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

Conformational analysis of difluoromethylornithine: factors influencing its gas-phase and bioactive conformations

• Matheus P. Freitas

Beilstein J. Org. Chem. 2026, 22, 237–243, doi:10.3762/bjoc.22.17

• preference arises primarily from hyperconjugative stabilization, particularly the σCH → σ*CN interaction, while steric effects modulate the relative stability among low-energy conformers. The gauche effect is intensified in the zwitterionic form due to electrostatic interactions. In contrast, the

• between natural localized molecular orbitals shows that structure 4 experiences the weakest steric repulsion, whereas structures 1–3 are among the most sterically crowded (Table 1). Several interactions contribute to this trend; notably, the nN/σCC interaction involving the NH₂ group geminal to the

• together with Lewis-type effects control the orientation of the difluoromethyl group, are summarized in Table S1 (Supporting Information File 1). As expected, σCH → σ*CN is the dominant interaction (>3 kcal mol−1) and is present in all type-I structures. When these interactions are summed for each

Configuration–packing synergy enabling integrated crystalline-state RTP and amorphous-state TADF

• Ruiyan Wang and
• Yunan Wu

Beilstein J. Org. Chem. 2026, 22, 224–236, doi:10.3762/bjoc.22.16

• phosphorescence emission was observed for the powder compared to the solution, suggesting that the RTP in the powder phase is influenced by intermolecular packing effects. This observation implies that the organization and interaction between molecules in the solid state play a crucial role in facilitating the

Screwing the helical chirality through terminal peri-functionalization

• Devesh Chandra,
• Sachin and
• Upendra Sharma

Beilstein J. Org. Chem. 2026, 22, 205–212, doi:10.3762/bjoc.22.14

• each other via hydrogen-bonding interaction, locking the relative orientation of the substrates producing the chiral [4]carbohelicene via peri-terminal functionalization (Figure 2). To examine the utility of the developed protocol, the reaction was scaled up to a 2 mmol scale and the product was

• phosphine oxide and the nitro-functionalized oxa[5]helicene. This ion-pairing interaction was also studied using NMR titration and Job’s plot analysis. The transition state depicted in Figure 3 was found to be most favorable providing the product with M-configuration. Looking ahead, these strategies may

Asymmetric Mannich reaction of aromatic imines with malonates in the presence of multifunctional catalysts

• Kadri Kriis,
• Harry Martõnov,
• Annette Miller,
• Mia Peterson,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2026, 22, 151–157, doi:10.3762/bjoc.22.8

• led to the use of multifunctional catalysts of “homocooperativity,” where multiple units of the same catalyst perform different but complementary roles [17]. These catalysts employing noncovalent interactions via hydrogen bonds and also possess Lewis basic and π–π-interaction sites have been highly

• , entry 17), further highlighting the importance of the pyridine ring containing protecting group. The interaction between catalyst E and the imine was further investigated by 19F NMR studies (see Supporting Information File 1). To further elucidate the role of noncovalent interactions, we conducted

• strengthened via hydrogen-bond-assisted halogen bonding [26][30]. Similarly, hydrogen bonds with the amidic proton are also possible. The direct effect of a specific interaction could not be determined based on the obtained data. The network of noncovalent interactions formed stabilizes the complex between the

Symmetrical D–π–A–π–D indanone dyes: a new design for nonlinear optics and cyanide detection

• Ergin Keleş,
• Alberto Barsella,
• Nurgül Seferoğlu,
• Zeynel Seferoğlu and
• Burcu Aydıner

Beilstein J. Org. Chem. 2026, 22, 131–142, doi:10.3762/bjoc.22.6

• theory (DFT) methods. The dyes also exhibit chemosensor properties, showing selectivity for cyanide via a Michael addition mechanism that causes the disappearance of the ICT band, and a significant color change was observed in both organic and aqueous media. In addition, the interaction mechanism between

• under ambient light. In addition, interaction mechanisms of dyes with cyanide were studied using the 1H NMR titration method, and it was determined that they interacted through an addition mechanism. Photophysical properties and interaction mechanisms of the compounds were also supported through density

• groups is disrupted. These results strongly suggest the addition of cyanide to the vinyl bridge. Furthermore, the color of dyes 2a–c, blue, green, and pink, respectively, under ambient light changed to yellow when interacting with cyanide. The interaction mechanism was determined by 1H NMR, and the

Total synthesis of natural products based on hydrogenation of aromatic rings

• Haoxiang Wu and
• Xiangbing Qi

Beilstein J. Org. Chem. 2026, 22, 88–122, doi:10.3762/bjoc.22.4

• substrate electronic environments [29]. Reactivity is governed by the electron density of arenes, which directly influences kinetics and product distributions [30][31]. The inability to generically modulate this interaction has confined most catalytic systems to narrow substrate scopes. Addressing this

Advances in Zr-mediated radical transformations and applications to total synthesis

• Hiroshige Ogawa and
• Hugh Nakamura

Beilstein J. Org. Chem. 2026, 22, 71–87, doi:10.3762/bjoc.22.3

• for the success of the reaction. DFT calculations suggested that in the transition state (TS1), a Cl–π interaction between the chlorine atom on the zirconocene catalyst and the aromatic ring of the substrate facilitated rapid halogen atom transfer (XAT), generating a radical at the C3 position of

• presence of a Cl–π interaction, which facilitates the facile XAT process. Since this step is accompanied by the formation of a strong Zr–Br bond [12], the overall process is exothermic (ΔGrxn = −22.6 kcal/mol) and provides the thermodynamic driving force for the reaction. Next, control experiments were

Sustainable electrochemical synthesis of aliphatic nitro-NNO-azoxy compounds employing ammonium dinitramide and their in vitro evaluation as potential nitric oxide donors and fungicides

• Alexander S. Budnikov,
• Nikita E. Leonov,
• Michael S. Klenov,
• Andrey A. Kulikov,
• Igor B. Krylov,
• Timofey A. Kudryashev,
• Aleksandr M. Churakov,
• Alexander O. Terent’ev and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2025, 21, 2739–2754, doi:10.3762/bjoc.21.211

• of nitric oxide (N2O2). These results allow us to think that the reaction pathway via nitrene C-s is less plausible compared to the interaction of radical A with 1a. Aliphatic nitro-NNO-azoxy compounds as potential NO donors and their in vitro fungicidal activity At the second part of our study, the

• of 0.1 V/s at 298 K. Free energy diagram of possible interaction pathways between 1a and dinitramide-derived radical A according to ωB97X-3c [94]/CPCM(MeCN) level of theory. Free energies ΔG and activation free energies ΔG≠ are given in kcal/mol. Dashed lines correspond to spin-state-changing

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

• imine reaction center. This makes the center softer, which favors the interaction with the amino group to generate the hexahydropyrimidine intermediate C. The methyl, ethyl and butyl substituents of intermediate B have a positive inductive effect, which increases with the lengthening of the alkyl chain

Mechanistic insights into hydroxy(tosyloxy)iodobenzene-mediated ditosyloxylation of chalcones: a DFT study

• Jai Parkash,
• Sangeeta Saini,
• Vaishali Saini,
• Omkar Bains and
• Raj Kamal

Beilstein J. Org. Chem. 2025, 21, 2703–2715, doi:10.3762/bjoc.21.208

• , the interaction of [PhIOH]+ with C at α-position is weaker and is evident by longer C–I bond lengths in Int1, i.e., 3.06 Å and 3.14 Å for chalcones with X = -Cl, -NO2, respectively (Table 2). In fact, this interaction is much weaker for chalcone with X = -NO2 that the reaction between chalcone and

• interaction between chalcone and [PhIOH]+ for Int1 and Int2. The significant lengthening of the I–OH bond facilitates removal of the -OH group from Int2 to form Int3. The dissociation of I–OH is an important step in the reaction mechanism which plays a significant role in the overall reaction. The chemical

• transformation of Int2 to Int3 involves the interaction between lengthened the I–OH bond with [PhIOH]+ furnished by the second dissociated molecule of HTIB. This interaction with subsequent removal of H2O results in the formation of iodosobenzene. The formation of iodosobenzene makes the transformation of Int2

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• )allylium tetrafluoroborate, which was then coupled to the C3 hydroxy group via Yamaguchi esterification. Global deprotection subsequently afforded ryanodine (1) in 10 steps, thus achieving this critical synthetic transformation. Although the interaction of ryanodine with intracellular calcium release

Isoorotamide-based peptide nucleic acid nucleobases with extended linkers aimed at distal base recognition of adenosine in double helical RNA

• Grant D. Walby,
• Brandon R. Tessier,
• Tristan L. Mabee,
• Jennah M. Hoke,
• Hallie M. Bleam,
• Angelina Giglio-Tos,
• Emily E. Harding,
• Vladislavs Baskevics,
• Martins Katkevics,
• Eriks Rozners and
• James A. MacKay

Beilstein J. Org. Chem. 2025, 21, 2513–2523, doi:10.3762/bjoc.21.193

• portion of the nucleobase (the isoorotamide) simply dissolved, or rotated away from the binding pocket, not forming the intended interaction with distal A base in silico (Figure 7A). In the case of Db2, the amide NH in the linker was apparently too far from the PNA backbone and did not form the intended

• stabilizing H-bond but rather formed a hydrogen bond with the U in the U–A base pair (ca. 2.2 Å, Figure 7B). This interaction resulted in pushing the entire residue towards the RNA backbone where the Io base could further bind to a phosphate which likely explains why Db2 shows the lowest triplex stability of

• , heterocycle of Db2 is rotated, placing its polar face towards solute and non-polar methyl group towards RNA. This results in the whole Db2 base being tilted, which breaks the intended stabilizing H-bond between the Db2 linker and the adjacent M. Db3 resulted in the best interaction in silico despite the low

Effect of a photoswitchable rotaxane on membrane permeabilization across lipid compositions

• Udyogi N. K. Conthagamage,
• Lilia Lopez,
• Zuliah A. Abdulsalam and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2498–2512, doi:10.3762/bjoc.21.192

• occurred mainly within the first 10 minutes and then plateaued for the following hour, indicating that the initial interaction drives most of the perturbation. In contrast, 4-E continued to promote release over time, reflecting larger and sustained membrane disruption. Comparing isomers, the difference in

Synthesis of the tetracyclic skeleton of Aspidosperma alkaloids via PET-initiated cationic radical-derived interrupted [2 + 2]/retro-Mannich reaction

• Ru-Dong Liu,
• Jian-Yu Long,
• Zhi-Lin Song,
• Zhen Yang and
• Zhong-Chao Zhang

Beilstein J. Org. Chem. 2025, 21, 2470–2478, doi:10.3762/bjoc.21.189

• formation of IN1. The radical cation IN1 served as the reference point for DFT investigations. As illustrated in Figure 2a, facilitated by a favorable radical cation–π interaction [31], IN1 proceeds to the first radical addition transition state (TS1), with an energy barrier of 8.3 kcal/mol. This leads to

• ). Further geometrical adjustment and conformational restriction of the transient structure enable the N9 nonbonding p orbital to align parallel to the σ(C19–C3)* orbital (Figure 2f, TS2 → F-10 → F-40 → IN3), which reinforces the hyperconjugative interaction. Facilitated by the bond stretching and bond-angle

• bending of the transient structure with a pseudo bicyclo[2.2.0]hexane unit, the favorable hyperconjugative interaction ultimately leads to cleavage of the C19–C3 bond (TS2 → IN3) and release of the ring strain. DFT analysis hereby explains that the orbital symmetry involved in this process does not