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

• tweezer H3 conjugate and a FITC-labeled H3 peptide pointed to very strong binding in the nanomolar range (Figure 3). Molecular modeling revealed that the tweezer moiety could easily reach Lys-121, but could bind to Lys-129 only in an energetically unfavorable, extended conformation. Indeed, mutation of

• to the backbone conformation since it strongly influences the conformation of the neighboring alanine. Position 3 should either be a phosphothreonine or a glutamine, and position 4 is preferred as Arg or Lys. The peptide affinity drops 3- or 4-fold when increasing the pH from 6.8 to 8.2, thus

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

• ideal gauche values and the absence of severely over-twisted dihedrals indicate a relatively low-strain conformation. In contrast, epoxide 9b exhibits a more distorted dihedral distribution, including a strongly twisted dihedral (≈90°) together with unevenly distributed gauche and near-planar torsions

• . This pattern is consistent with a less favourable, distorted boat-chair (or twist-boat-chair-like) conformation, associated with increased torsional strain, thereby disfavouring formation of 9b relative to 9a. Next, we turned our attention to the methanolysis of the mixture of isomeric epoxides 9. A

• -twisted dihedral angle (τ3 = 94°), indicating a moderately distorted boat-chair conformation. In contrast, TS2 exhibits a characteristic twist-boat-chair arrangement, evidenced by the co-existence of a strongly over-twisted segment (τ2 = 101.8°) and a nearly planar dihedral (τ6 = 4.0°). A similar trend is

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

• information for a better understanding of the NMR spectra. In contrast to the planar benzene ring of melifoliones, the para quinol ring in 4 adopts a flat but rigid boat conformation. However, the sp3-hybridized C-10b leads to greater flexibility of the whole molecule. Therefore, it is easier for the

• cyclohexane ring to deviate from a chair to a twisted boat conformation by rotating around the C-7/C-8-axis. As a result, the orientation of the geminal protons at these positions can change more easily between a pseudo-axial (ax) and a pseudo-equatorial (eq) position, and the difference in chemical shift

• rigid chair conformation of the cyclohexane ring. The 13C NMR spectrum of 11 (Table 3) shows 15 signals that could be clearly assigned after evaluating the HSQC and HMBC spectra. In the HMBC spectrum, cross peaks occur for C-3 with H-4’ and with the protons of both geminal CH3 groups at C-1. Furthermore

Synthesis and uranyl(VI) extraction performance of a calix[4]pyrrole–tetrahydroxamic acid receptor

• Sara Karnib,
• Rana Baydoun,
• Wissam Zaidan,
• Nancy AlHaddad,
• Omar El Samad,
• Bilal Nsouli,
• Francine Cazier-Dennin and
• Pierre-Edouard Danjou

Beilstein J. Org. Chem. 2026, 22, 486–494, doi:10.3762/bjoc.22.36

• uranyl ion and the Z-isomer of hydroxamic acid effectively shifts the Z/E equilibrium [70] towards the Z-conformation through a metal-induced fit mechanism [71][72]. Consistent with known hydroxamate coordination chemistry, coordination-induced deprotonation of the hydroxamic acid at low pH provides 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

• residues. Cysteines possess thiol side chains that exhibit strong affinity for gold, enabling them to form stable bonds with metal surfaces [21]. Such interactions may disrupt the native conformation of cysteine-containing proteins or peptides, potentially impairing the structural integrity of the CoREST

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

• 27.92 ± 3 µM and 23.06 ± 3 μM, respectively. Molecular docking simulations revealed that NAP-SePh and NAP-Se(n-Oct) show binding affinities of −10.39 and −8.53 kcal/mol for the (1M17) active, and −10.66 and −10.59 kcal/mol for the (4HJO) inactive conformation of the tyrosine kinase domain of the

• single-crystal XRD coordinate file, whereas the structure of compound 8 was derived from DFT energy minimisation. Both ligand structures were converted into PDB format for molecular docking studies using the crystal structures of EGFR tyrosine kinase in active conformation (1M17) and inactive

• conformation (4HJO). The docking results revealed that both ligands fit well within the binding pocket of the EGFR tyrosine kinase domain. The binding interactions were further validated by comparison with the crystal structures of the active (1M17) and inactive (4HJO) forms of EGFR complexed with the co

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

• in the 1H NMR spectra with respect to those from the aromatic units bearing no electron-withdrawing groups. This uncommon signal position may indicate a specific time-averaged conformation of the calixarene core in compounds 12 and 13 due to the presence of the bulky TBS-protected propargyl groups in

• conformational interconversions), thereby favoring or disfavoring the C4v-symmetric ‘ideal’ cone conformation of the calixarene core required for capsule formation [59]. To check this, 1H NMR spectra from the CDCl3 solutions of multifunctionalized calixarenes 47–51 and their 1:1 mixtures with the known O

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

• . Its characteristic hydrogen-bonding ability strongly influences molecular conformation and intermolecular interactions, while the exceptional thermodynamic stability of the amide moiety contributes to its persistence in diverse atmospheric and biological environments [1][2][3][4][5]. Owing to these

Synthesis of tricyclic fused pyrrolidine nitroxides from 2-alkynylpyrrolidine-1-oxyls

• Mark M. Gulman,
• Yuliya F. Polienko,
• Sofia Yu. Trakhininа,
• Yuri V. Gatilov,
• Tatyana V. Rybalova,
• Sergey A. Dobrynin and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2026, 22, 344–351, doi:10.3762/bjoc.22.22

• that this methylene fragment has a more fixed conformation, consistent with the annulated structure (Figure 4). Nitroxides are known to decay in biological systems; the major mechanism is chemical reduction with cellular antioxidants (ascorbic acid and glutathione) and enzymatic systems [34]. The rate

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

• . Taking into account that the conformation of the actin monomer in the described structures is basically the same, the structure of non-muscle β-actin (8DNH, 2.99 Å) obtained by cryo-electron microscopy was used for this study. Docking was performed to both known clefts (hydrophobic or target-binding one

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

• decarboxylase and as a therapeutic agent against African trypanosomiasis. Beyond its pharmacological importance, DFMO provides a valuable model for examining how fluorine substitution governs molecular conformation. A comprehensive quantum-chemical study was performed to elucidate the origins of DFMO’s

• interactions (typically σCH → σ*CF) that stabilize conformations in which the C–F bonds adopt a gauche orientation relative to polar bonds, such as C–N or C–O [8][9][10]. In DFMO, the difluoromethyl group is directly connected to the ornithine backbone, and its conformation is expected to be shaped not only by

• complex. Elucidating this interplay is essential for rationalizing DFMO’s inhibitory potency and may also offer broader insight into how fluorinated substituents control molecular conformation in biologically relevant environments. Although the biological milieu is known to induce only minor structural

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

• reasonably inferred that, in the amorphous state, intermolecular π–π stacking interactions are significantly suppressed. This suppression of π–π interactions, along with a more disordered molecular conformation and microenvironment, makes it difficult to establish effective rigid constraints necessary for

Improved synthesis and physicochemical characterization of the selective serotonin 2A receptor agonist 25CN-NBOH

• Adrian G. Rossebø,
• Hannah G. Kolberg,
• Anders E. Tønder,
• Louise Kjaerulff,
• Poul Erik Hansen,
• Karla A. Frydenvang,
• Jesper Østergaard and
• Jesper L. Kristensen

Beilstein J. Org. Chem. 2026, 22, 175–184, doi:10.3762/bjoc.22.11

• conformation is less polar and more rigid in nature, and thus reducing the energetic penalty that is typically associated with this process. The possible impacts of such IMHBs on membrane permeability are well recognized [16][17]. Therefore, it appeared reasonable to speculate that a possible IMHB of 1 could

• isotope effect experiments, this suggests that under physiological conditions, a significant fraction of 1 will be able to adapt a conformation with an IMHB – the species that is most amenable to cross biomembranes. It should be mentioned that there could also be an IMHB present in the protonated form

Design and synthesis of an axially chiral platinum(II) complex and its CPL properties in PMMA matrix

• Daiki Tauchi,
• Sota Ogura,
• Misa Sakura,
• Kazunori Tsubaki and
• Masashi Hasegawa

Beilstein J. Org. Chem. 2026, 22, 143–150, doi:10.3762/bjoc.22.7

• than the 80–100° range typically reported for the most stable conformation of binaphthyl groups [24]. In contrast, the dihedral angles between the binaphthyl unit and the coordination plane were 54° and 52°, respectively. The UV–vis spectral simulation based on electronic transition obtained from time

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

• cyclopropane ring is probably a consequence of the formation of a sterically hindered carbanion II in a conformation with an anti-periplanar position of the bulky substituents – bromine and a trichloromethyl group (Scheme 6). Due to the steric reasons, the anion in this conformation is selectively protonated

• bromine. The cyclization step from this conformation leads to trans-cyclopropanes. X-ray diffraction analysis data for compounds 2, 3, 9a, and 9b convincingly confirm the accepted structures, the position of cyclopropane protons, and the relative configurations of asymmetric atoms (Figures 2–5). It should

• enatiomeric pair S,R,S/R,S,R is realized, and in crystal 9b – S,R,R/R,S,S. The main geometric parameters (bond lengths and valence angles) and the conformation of independent molecules in crystals of 2, 3, 9a and 9b coincide within the experimental errors, so Figures 2–5 show the geometry of one of 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

• 81 was prepared via a Polonovski–Polish reaction and isomerization, which, when adopting the proper conformation, spontaneously underwent an intramolecular [4 + 2] cycloaddition to construct the unsaturated bridged ring of (±)-keramaphidin B in a single transformation. Subsequently, the iminium ion

• oxygen atoms from the substrate and the metal catalyst, which fixed the conformation of the polycyclic scaffold. As a result, the top face is sterically less favored, thereby hydrogen approaches from the opposite face. The subsequent addition of another two equivalents of hydrogen also supported this

Reactivity umpolung of the cycloheptatriene core in hexa(methoxycarbonyl)cycloheptatriene

• Dmitry N. Platonov,
• Alexander Yu. Belyy,
• Rinat F. Salikov,
• Kirill S. Erokhin and
• Yury V. Tomilov

Beilstein J. Org. Chem. 2026, 22, 64–70, doi:10.3762/bjoc.22.2

• hydrazonocycloheptatriene 10k. Notably, dihydroindazoles 8 and 9 are similar to that previously formed from 1 [17]. In this investigation the most questionable is the attack onto the i-position. In our previous studies we have substantially investigated the geometry of anion 2 in the most stable conformation, which has a

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

• (Figure 2 and Figure 3), the piperidone ring has a half-chair conformation in which the pseudo-equatorially located trifluoromethyl group is a conformational anchor. The five atoms of the six-membered piperidone ring are coplanar, and the trifluoromethyl-substituted carbon atom С(8) is significantly

• deviated by more than 0.5 Å above or below the ring plane. Accordingly, the adjacent hydroxy substituent has a pseudo-axial position. The hexahydropyrimidine ring in bicycles 4аcc, 4аct, 4аtt, 4аtc, 4dct has a chair conformation, and the oxazolidine ring in heterocycles 5ctc, 5ctt has an envelope

• conformation, with a deviation of the oxygen atoms O(1) by 0.5 Å for 5ctc and nitrogen atoms N(1) by 0.4 Å for 5ctt. In trans-junction, bicycles 4att, 4atc (Figure 2c,d) have a flattened fixed skeleton with a dihedral angle of 24.8–27.3° (see Table S9, in Supporting Information File 1), in which the

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

• (Scheme 1, Compound A, X = -OCH3), the nucleophilic addition of the tosylate to carbenium ion is found to be syn. An anti-addition was also studied but it is found to be an unfavourable conformation for subsequent aryl migration [34]. On account of this, the current study focuses on the syn-addition

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

• conformation, causing the nuclei on each side of the molecule to experience different local magnetic environments. In this case, four smaller peaks – each corresponding to a distinct carbon atom – should be observed. The absence of these peaks could be explained by longer relaxation times associated with the

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

• signatures of peptide backbone conformation [27][28][29]: a random coil typically shows a negative band near 198 nm and a positive band near 218 nm; an α-helix exhibits characteristic minima at 208 nm and 222 nm and a maximum near 192 nm; β-sheet structures are often indicated by a single minimum between 210

Ni-promoted reductive cyclization cascade enables a total synthesis of (+)-aglacin B

• Si-Chen Yao,
• Jing-Si Cao,
• Jian Xiao,
• Ya-Wen Wang and
• Yu Peng

Beilstein J. Org. Chem. 2025, 21, 2548–2552, doi:10.3762/bjoc.21.197

• ] by flash column chromatography in 30% yield. The stereocontrolled formation of aryltetralin 13 could be attributed to an adoption of a pseudo-half-chair conformation 5a. Finally, the final step towards the total synthesis of (+)-aglacin B (2) was achieved by treatment with BF3·Et2O as the Lewis acid

Rapid access to the core of malayamycin A by intramolecular dipolar cycloaddition

• Yilin Liu,
• Yuchen Yang,
• Chen Yang,
• Sha-Hua Huang,
• Jian Jin and
• Ran Hong

Beilstein J. Org. Chem. 2025, 21, 2542–2547, doi:10.3762/bjoc.21.196

• formyloxy group on the N atom in the unstable intermediate 13 serves as electron-withdrawing group to facilitate fragmentation when removal of the acidic proton at C2 was initiated. Although the reduction of enone 14 could provide the requisite stereoisomer, the rigid conformation of such bicyclic [4.3.0

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

• functionalization of the calix[4]arene skeleton blocked in cone conformation, as evidenced by the AX system (3.13 and 4.26 ppm) for the bridged CH2 protons. Spontaneous self-assembly Due to the amphiphilic nature, compound 3 could spontaneously self-assemble in aqueous medium. This was confirmed by dynamic light

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

• details see Supporting Information File 1). The Db nucleobases were individually incorporated into the PNA model oligonucleotide and subjected to 50 ns unrestricted Desmond molecular dynamics. Pictures from the molecular dynamics simulations shown in Figure 7 represent the conformation of the PNA bases

• flexibility. Yet, for the Hoogsteen hydrogen bonding to occur using distal recognition monomers, the entirety of the flexible linker must enter the major groove being forced into a conformation that no longer is freely rotating. Additionally, these longer chains bring in potential issues of steric conflict