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

• sought confirmation of the structures of the minor and major diastereomers in our own hands. Noting that preparation of sulfides by double conjugate addition of Na2S or NaSH has been widely studied, and that the stereochemical assignments presented therein are in some cases supported by X-ray

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

Anti-invasive and cytotoxic evaluation of a (+)-pinoresinol-based semisynthetic library against glioblastoma

• Chen Zhang,
• Kah Yean Lum,
• Jonathan M. White,
• Paul I. Forster,
• Nicholas Booth,
• Sunita A. Ramesh and
• Rohan A. Davis

Beilstein J. Org. Chem. 2026, 22, 691–704, doi:10.3762/bjoc.22.54

• planar structure assignment for 5. Moreover, the relative configuration of the semisynthetic derivative 5 was assigned following ROESY data analysis. Following the slow evaporation of a methanolic solution of (+)-eudesmin (3), suitable crystals were obtained for X-ray crystallographic studies (Figure 4

• (MeOH) λext (Δε) 224 (2.71), 291 (−2.11); see Supporting Information File 1 for 1H (800 MHz) and 13C NMR (200 MHz) data in CDCl3; LRESIMS m/z: [M + Na]+ 549; HRESIMS m/z: [M + Na]+ calcd for C30H38NaO8, 549.2459; found, 549.2458. X-ray crystallography analysis of (+)-eudesmin (3) Intensity data were

• ), which enabled the absolute configuration of 3 to be assigned as 7S,8R,7'S,8'R. Moreover, this is the first report of a crystal structure of (+)-eudesmin (3). In 2015, Lu et al. reported the purification and full characterization of both enantiomers of eudesmin from Acorus tatarinowii, along with the X

Synthesis of depressin, cryptomeridiol and 4-epi-cryptomeridiol enabled by a terpenoid chiral pool-producing platform

• Yao Kong,
• Tao Wang,
• Chen Wang,
• Pengcheng Zhang,
• Yuanning Liu,
• Kaibiao Wang,
• Fen Liu,
• Hongli Jia and
• Zhengren Xu

Beilstein J. Org. Chem. 2026, 22, 683–690, doi:10.3762/bjoc.22.53

• derivative 16 (CCDC 2470579) as a brownish-yellow needle suitable for X-ray diffraction (Scheme 2b) [56][57], which confirmed the absolute configuration of the casbene skeleton and the position of the first allylic oxidation. It is also interesting to note that the three double bonds in this molecule are

• -cryptomeridiol (3). Synthesis of depressin (1), cryptomeridiol (2), and 4-epi-cryptomeridiol (3). a) Synthetic route of 1 starting from casbene (4). b) Preparation of 2,4-nitrophenylhydrazone derivative of 13-ketocasbene (9) for X-ray diffraction. c) Synthetic route of 2 and 3 starting from germacrene A (5

• ). Supporting Information Supporting Information File 5: Materials, synthetic methods and copies of NMR spectra for all compounds. Supporting Information File 6: X-ray crystal structure of 16. Funding We are grateful to the National Natural Science Foundation of China (No. 82574274) for the financial support.

Harnessing light energy with molecules

• Grace G. D. Han,
• Mogens Brøndsted Nielsen and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2026, 22, 680–682, doi:10.3762/bjoc.22.52

• -ray-induced isomerization within micelles generated from two different photosurfactants (containing either an azobenzene or arylazopyrazole photoswitch), thereby creating guidelines for using small-angle X-ray scattering to study photoresponsive materials of potential applications in solar energy

• another publication, Leung and co-workers [11] describe how amphiphilic donor–acceptor Stenhouse adducts can be employed in supramolecular nanostructures controlled by visible light, which is of particular interest for the development of biomedical materials. Jones, Evans, and co-workers [12] studied X

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

• other biomolecules) where no experimental structure has been reported. While the accuracy of these models continues to increase with time, protein structures modelled on experimental data (X-ray crystallography, cryo-electron microscopy) still remain the gold standard as starting points for structure

Towards the targeted protein degradation of CK2: design and synthesis of CAM4066-based PROTACs

• Sophie Day-Riley,
• Sona Krajcovicova,
• Aryaman Raj Sokhal,
• Jan L. Venne,
• Paul Brear,
• Marko Hyvönen,
• Benjamin C. Whitehurst,
• Jason S. Carroll and
• David R. Spring

Beilstein J. Org. Chem. 2026, 22, 611–619, doi:10.3762/bjoc.22.47

• Biophysical and X-ray crystallographic facilities at the Department of Biochemistry for access to instrumentation. We thank Diamond Light Source for access to beamline (proposal ID mx25402). Funding S. Day-Riley is grateful AstraZeneca Cambridge for a studentship and financial support. S. Krajcovicova is

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

• configuration of (–)-2b Levorotatory AMD/KR product (–)-2b, which was obtained as in entry 8, Table 1 using Mo/(R)-L1 precatalyst, was recrystallized by slow diffusion of pentane into the concentrated diethyl ether solution. Crystals of (–)-2b were grown as light-yellow blocks. The X-ray crystallography

• ], reveals that the molybdenum-catalyzed asymmetric metathesis reactions are powerful tools to control planar chirality in various transition-metal complexes. ORTEP drawing of the X-ray structure of (S,S)-(–)-2b with atom numbering (thermal ellipsoids set at the 30% probability level). Selected bond lengths

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

• ; 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

• by computational modeling (MD and QM/MM simulations) as well as structural biology (NMR/X-ray). Following our powerful concept of reinforcing natural peptide–protein interactions by tweezer conjugation [9][10], we envisaged to attach molecular tweezers to the histone H3 terminus at a distance which

• . Crystallizations with this compound and the truncated survivin constructs 1–122 and 1–127 were finally successful and yielded high-resolution X-ray structures (Figure 4) [15]. The structures of both survivin truncation mutants look very similar, both have a survivin dimer in the asymmetric unit, and the H3 peptide

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

• -ray analysis (Figure 2) [25]. X-ray analysis of azido compound 10 confirmed the trans configuration of the azide group with chloride and the cis configuration with the acetate. Our suggested mechanism for the ring-opening of the epoxides 9 with HCl(g) in MeOH proceeded as described in Scheme 3. As

• NOESY experiments or the other 2D NMR conducted. Compound 11 is not a single crystal, so the determination by X-ray analysis of its structure was not possible. We strongly assume that the structure of 11 is based on the methanolysis mechanism of the epoxide 9a (Scheme 3). In order to elucidate the

• , 1239, 1015, 720; HRESIMS (m/z): [M+ + Na] calcd for C17H19ClN4O6, 433.0891; found, 433.0885. Some important bioactive molecules with an azide group. The X-ray crystal structure of 10. Relative free energy profile for the methanolysis of the isomeric epoxides 9. Mulliken charge analysis of protonated

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

• contraction of the acetyl phenol to a furanone ring, forming the derivatives 11 and 12, whose structures were confirmed by X-ray analysis. A hypothetical mechanism for the oxidative ring contraction is proposed. 11 and 12 are the first representatives of new heterocyclic ring systems that have not previously

• . Further oxidation of the hydrate d results in the spirofuran e [13]. After ferricyanide oxidation of e, the 3-C dicarbonyl residue splits off as pyruvate [14], leaving the spirofuranone 11 as a stable product. Cristallographic investigation A problem arose during the X-ray crystallography of 11. In

• addition to 11 DMF and an isomeric compound 12 were identified in the unit cell (Figure 3). Single-crystal X-ray diffraction data were collected for all samples using a Synergy diffractometer (Rigaku Oxford Diffraction) equipped with a photon-counting detector system [15]. Despite careful selection and

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

• pentacoordinate or hexacoordinate structure, as shown by X-ray crystallographic studies. Consequently, to bind UO22+ effectively, a ligand must present donor atoms positioned to match the uranyl equatorial coordination sites [76]. Hydroxamic acids act as bidentate ligands, with each functional unit offering two

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

• CoREST complex that encompasses HDAC1/2, the co-repressor of REST (CoREST) and the lysine-specific demethylase 1 (LSD1). Cryo-EM and small angle X-ray scattering revealed that the CoREST complex exists as a bi-lobed structure [10]. Enzyme kinetics studies showed that HDAC1 and LSD1 do not act

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

• anticancer drug target. Compound 968 is a glutaminase inhibitor that is widely used to probe cancer cells’ dependence on glutaminase activity. Here, we show by NMR spectroscopy and X-ray crystallography that the reported benzo[c]phenanthridine structure of compound 968 is incorrect; its true structure is the

• ] and the substrate scope of diketone, arylamine, and arylaldehyde was widened over the subsequent decades [25][26][27]. However, later reports by Martinez et al. [28] using X-ray crystallography and Kozlov et al. [29][30] using NOESY NMR showed that this three-component cyclocondensation reaction does

• synthetic material and solved the structure by X-ray crystallography. The structure that fits the diffraction data is the benzo[c]acridine isomer 2 (Figure 3C). From this, we conclude that the structure of compound 968 is not the commonly accepted benzo[c]phenanthridine 1 but is instead the benzo[c]acridine

Synthesis and stereochemical analysis of dynamic planar chiral oxa[7]orthocyclophene

• Yukiho Hashimoto,
• Yuuya Kawasaki,
• Kazunobu Igawa and
• Katsuhiko Tomooka

Beilstein J. Org. Chem. 2026, 22, 436–442, doi:10.3762/bjoc.22.30

• X-ray crystallographic analysis was performed (CCDC 2513894). The solid-state structure of 1ac shows that the phenyl group on the E-alkene is directed antiparallel to the fused benzene ring. The dihedral angle of the alkene moiety (∠C4–C5–C6–C7) of 1ac is 146.4°, which is distorted by 33.6° from an

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

• structurally characterised by single-crystal X-ray diffraction analysis. The anticancer potential of the NAP-SePh and NAP-Se(n-Oct) was evaluated using an in vitro cell viability assay with MDA-MB-231 triple-negative breast cancer (TNBC) cells. The IC₅₀ values for compounds NAP-SePh and NAP-Se(n-Oct) were

• . However, as shown in Supporting Information File 1, Figure S19, a representative fragment ion with a m/z value of 318.0028 could be matched with naphthalimide selenenium cation, having a calculated m/z value of 318.0028. Single-crystal X-ray diffraction analysis of compound 7 A single crystal of compound

• 7 was obtained by slow evaporation of a chloroform–methanol mixture (1:3 v/v). Single-crystal X-ray diffraction analysis revealed that compound 7 crystallises in the triclinic crystal system with the space group . The crystal structure of compound 7 is shown in Figure 2a. It shows a typical V-shaped

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

• calixarene 12, which is additional evidence for its structure. The structure of trinitrated calix[4]arene 16 having a single TBS-protected propargyl group at the narrow rim was unambiguously established from X-ray diffraction data. Suitable crystals were collected upon slow evaporation of a dichloromethane

• determined using 2D NMR and X-ray diffraction data, contributing to a general understanding of the selectivity of nitration when applied to calixarenes containing bulky narrow-rim substituents. The functionalization capabilities of the propargylated/2-azidoethylated p-aminocalix[4]arenes were demonstrated by

• Supporting Information File 18: Synthesis details, copies of 1H and 13C NMR spectra of novel compounds, details of X-ray diffraction measurements and crystal structure data. Supporting Information File 19: Crystallographic information file for compound 16. Supporting Information File 20: Crystallographic

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

• protons of the dimethylamino group and the methylene protons of the propargyl moiety. The structure of nitroxide 2d was confirmed by single crystal X-ray analysis. (Figure 1, CCDC 2512649). The nitroxides 2a–f were used to synthesize tricyclic nitroxides 4a–f. The mesylation was carried out in the

• are characterized with smaller triplet splitting, aN = 1.43–1.46 mT, while hfc on hydrogen reach 0.26–0.31 mT, with the exception of 4b (0.22 mT). The structures of nitroxides 4a, 4b, and 4c were confirmed by single crystal X-ray crystallographic analysis (Figure 2, CCDC 2512650–2512652). Similar

• dioxide in tetrahydrofuran gave vinyl ether 8, which was isolated with 50% yield (Scheme 4). The structure of the product 8 was confirmed by X-ray crystallographic analysis (Figure 3, CCDC 2512653). Formation of 8 apparently occurs via cyclization of alkynal 7. The formation of vinyl ethers has been

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

• X-ray diffraction analysis (XRD) for two adducts, followed by Hirshfeld surface analysis. The antiproliferative effect of the synthesized compounds against cancer cell lines was assessed. Keywords: alloxan; antiproliferative activity; azomethine ylides; 1,3-dipolar cycloaddition; maleimides

• diffusely in the cytoplasm of treated cells in up to 87%) and changes in the number of filopodia-like deformations (increased up to 61% after cultivation). Schematic structures of endo- and exo-adducts of spirobarbiturates 4. X-ray crystal structures of compounds 4b (CCDC 2391172, left) and 4c (CCDC 2391171

• Information File 38: General information, experimental procedures, characterization data, X-ray data and biological activity data. Acknowledgements This research made use of resources from the Centre for Magnetic Resonance, X-ray Diffraction Centre, Centre for Chemical Analysis and Materials of Saint

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

• Abstract A twisted D–π–A molecule, PI-Cz 1, was designed and synthesized using phthalimide as the acceptor, carbazole as the donor, and a phenylene bridge. Single-crystal X-ray diffraction revealed a markedly non-coplanar skeleton. Calculations based on the crystallographic geometry and frontier-orbital

• obtained through the method of slow solvent evaporation, which allows for the formation of high-quality crystals suitable for detailed structural analysis. The crystal structure of 1 was thoroughly characterized using single-crystal X-ray diffraction (CCDC 2492630). This technique provides precise three

• Figure 5b. This indicates that the specific molecular arrangement necessary for RTP was disrupted upon melting and subsequent rapid cooling, suggesting that the ordered structure in the solid phase is essential for the RTP phenomenon. In addition to the optical measurements, powder X-ray diffraction

Base-promoted deacylation of 2-acetyl-2,5-dihydrothiophenes and their oxygen-mediated hydroxylation

• Vladimir G. Ilkin,
• Margarita Likhacheva,
• Igor V. Trushkov,
• Tetyana V. Beryozkina,
• Vera S. Berseneva,
• Vladimir T. Abaev,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2026, 22, 192–204, doi:10.3762/bjoc.22.13

• dihydrothiophenes 4a–f formed only deacetylated products 5a–f when the reaction was performed in an oxygen saturated ethanolic solution in the presence of sodium ethoxide. Experimental X-ray structure determination of 5g 5g: Crystal data for C17H18N2O2S (M = 314.40 g/mol): monoclinic, space group P−1, a = 9.3076 (5

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

• solid form Crystals of 1·HCl were grown from an ethanolic solution, and the crystal structure was determined by single-crystal X-ray diffraction (SCXRD, Figure 2). As seen in Figure 2a, 1·HCl adopts a twisted U shape and is involved in three hydrogen bonds. Therein, the ammonium N atom interacts with

• ). Notably, the crystal structure shows that there are no water molecules of crystallization present, nor are any other solvent molecules incorporated into the crystal packing. When comparing the diffractogram obtained by SCXRD (Figure 3, green) with that obtained by X-ray powder diffraction (XRPD) of 1·HCl

• (4 °C) overnight, the solids were collected by vacuum filtration and dried under high vacuum. In this way, approximately 60% of the starting material was recovered as a white solid. SCXRD Crystals of 1·HCl were grown by slow evaporation of a solution in EtOH at rt. A single crystal suitable for X-ray

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

• spectroscopy, as well as high-resolution mass spectrometry (HRMS). Due to its low solubility, single crystals suitable for X-ray crystallographic analysis could not be obtained. Spectroscopic analysis and DFT calculations To elucidate the electronic structure of the platinum(II) complex, UV–vis absorption

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

• group; X-ray; Introduction Trichloromethyl groups containing compounds are widely used in the organic synthesis of practically significant substances [1][2]. Based on them, methods have been developed for the synthesis of hard-to-access 5-aminoisoxazoles [3], α- and γ-heterosubstituted unsaturated

• 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

• be noted that the lengths of the C1–C2 (1.470(2)–1.491(4) Å) and C2–NO2 (1.472(4)–1.486(2) Å) bonds according to X-ray diffraction analysis in the molecules of nitrocyclopropanes 2, 3, 9a, and 9b turn out to be close to those in the molecules of nitrospirocyclopropanecarboxylates (C1–C2 (1.464(1

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

• excellent yield, the structure being confirmed using single crystal X-ray analysis (CCDC 2495984). Bromination afforded a mixture of symmetric cycloheptatriene 4b and norcaradiene 6b, while intermediate cycloheptatriene 5b was not even observed. Iodination gave exclusively norcaradiene 6c. Previously

• norcaradiene product in the case of benzylation, unlike in the close analogues, is due to a steric repulsion. The structure of norcaradiene 6f was confirmed through single crystal X-ray analysis (CCDC 2495985). Allylation of anion 2 was followed by intramolecular [4 + 2]-cycloaddition in norcaradiene 6g to

• form caged tetracyclodecene 7g similar to that previously obtained from anion 1 [17] and also confirmed through single crystal X-ray analysis (CCDC 2496140). Using aryldiazonium salts as electrophiles afforded an even more complicated cascade process. Initial reactions with phenyl- or 4-substituted