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

• vinylferrocenes and of over 1000 for the vinylphosphaferrocenes. In this article, we would like to report the analogous asymmetric metathesis dimerization/kinetic resolution of a series of racemic planar-chiral vinylcymantrenes (rac-1a–c). It was found that the chiral molybdenum-alkylidene precatalysts Mo/(R)-L1

• racemic planar-chiral 2-substituted vinylcymantrene substrates rac-1a–c A series of racemic planar-chiral vinylcymantrene substrates rac-1a–c were prepared as outlined in Scheme 2. Whereas enantioselective synthesis of 2-substituted formylcymantrenes 5a–c, precursors to 1a–c, were reported [33][34][35

• ], racemic 5a–c were prepared in the same ways starting with rac-3. Vinylcymantrene substrates rac-1a–c were obtained in 68–79% yields by the Wittig methylenation of rac-5a–c. The moderate yields could be attributed to the volatility of rac-1a–c. Molybdenum-catalyzed asymmetric metathesis dimerization (AMD

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

• ), with the phosphorylated histone H3 N-terminal peptide. Fluorescence polarization measurements revealed a nanomolar affinity of the BIR domain for the peptide-tweezer, depending on the presence of lysine residue 121, as proven by the K121A mutant of survivin. Two crystal structures of C-terminally

• tweezers. Importantly, the H3 N-terminus had to be fully conserved (vide infra), so that covalent attachment of the tweezer moiety had to occur at the peptide C-terminus. A first prototype 1 could be realized with a C3-spacer and click coupling between azidopropylamide on Lys-4 at the peptide's C-terminus

• . Hence, we designed the truncation constructs 1–122, 1–127 and 1–134 that shorten the flexible C-terminal helix of survivin. All new constructs showed a much better expression and crystallization behavior. Fluorescence polarization measurements with the FITC-labeled H3 peptide confirmed that constructs 1

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

• , Merck). TLC was carried out on Merck 0.2 mm silica gel 60 F254 analytical aluminium plates. (1R*,8S*,Z)-9-Oxabicyclo[6.1.0]non-4-ene (6) A magnetically stirred solution of cis,cis-1,5-cyclooctadiene (5, 1.00 g, 9.24 mmol) in 50 mL dichloromethane was cooled to 0 °C. m-CPBA (2.20 g, 77%, 9.82 mmol) and

• NaHCO3 (0.78 g, 9.29 mmol) were added to the solution and stirred for 1.5 hours. Subsequently, 50 mL of 1.5 M NaOH solution was added and the reaction mixture was stirred for 15 min at 0 °C, then extracted with dichloromethane (4 × 30 mL). The organic layer was dried over Na2SO4, filtered, and evaporated

• NMR (100 MHz, CDCl3) δ 130.3, 127.5, 73.1, 66.8, 32.4, 29.7, 23.5, 23.1. (1S*,8S*,Z)-8-Azidocyclooct-4-en-1-yl 4-nitrobenzoate (8) The azidol 7 (0.50 g, 2.99 mmol) was dissolved in 9 mL of anhydrous pyridine and the solution was cooled to 0 °C. p-Nitrobenzoyl chloride (1.11 g, 5.98 mmol) and 4

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

• signals detected in the 13C NMR spectrum of 4 (Table 2) could be assigned by careful analysis of the 2D-NMR spectra (HSQC and HMBC). The position of the acetyl group was confirmed by a cross peak between C-2 and the protons of the acetyl-methyl group in the HMBC spectrum and by interactions between the

• acetyl-methyl group and the methyl group at C-9 as well as between H-4 and one of the geminal methyl groups at position 6 in the NOESY-spectrum. This allowed us to clarify the structure of 4 as an oxidation product of melifolione B (2). We suggest the following name: 2-acetyl-6a,7,8,9,10,10a-hexahydro

• 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

Get a better glimpse on sequential photoreactions of trisnorbornadienes with ¹⁹F NMR spectroscopy

• Julian Felix Maria Hebborn,
• Ben Eric Merten,
• Thomas Paululat and
• Heiko Ihmels

Beilstein J. Org. Chem. 2026, 22, 527–534, doi:10.3762/bjoc.22.38

• the physicochemical parameters of the light energy storage and release, the thermally induced cycloreversion of 2f0,3 was investigated. Analysis of the cycloreversion at different temperatures revealed a half-life, t1/2, of 55 d at 25 °C, an activation enthalpy ΔH = 99.4 kJ/kg, and an activation

• entropy of ΔS = −42 J/K mol (see Supporting Information File 1, Figure S2). The energy density of trisquadricyclane 2f0,3 was determined with simultaneous thermal analysis (STA) with a heat release of 458 kJ/kg. Additionally, a second exothermic peak (>150 °C) correlated with a significant decrease in

• ]heptadien-2-yl)-1,3,2-dioxaborolane (1e, 501 mg, 2.30 mmol), Pd(PPh3)4 (66.5 mg, 57.5 µmol, 5 mol %), THF (5.0 mL), and aq. NaOH (5.7 mmol, 2.7 M, 2.1 mL) was stirred at 80 °C for 16 h under anaerobic conditions [22]. After cooling the emulsion to room temperature, EtOAc (15 mL) was added and the organic

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• . Protection of the free alcohol unit enabled the transformation towards 55, which involved the reduction of lactone to lactole, protection of the alcohol as acetate, BF3·Et2O-mediated C-allylation of the aldehyde (via oxocarbenium intermediate) and cyclization (oxy-Michael reaction). Hydroboration–oxidation

• under basic conditions triggered an Achmatowicz rearrangement (shown in Scheme 8, below) to assemble a hydropyranone ring [83]. Eventual acetylation of the free alcohol units afforded 70 in 3:1 dr. C-Glycolysation with allyl-TMS and oxidative cleavage of the PMB moiety yielded 71. The stereochemistry of

• using acetic anhydride. Oxidative cleavage of olefin 73, followed by treatment with ʟ-proline led to an intermediate β-aldehyde with inverted stereochemistry at the β-C (4:1 dr). Subsequent reduction with NaBH4 yielded alcohol 74. Piv-protection of the primary alcohol, reductive deprotection of the Bn

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

• calixarene tetraethylacetate [53]. In the original procedure, KOH was added at −5 °C, and the mixture was stirred for 5 hours at this temperature, followed by 5 days of stirring at room temperature. In our hands, both the addition of KOH and stirring were performed entirely at room temperature, and 1H NMR

• %). The structure of PCP HA was fully characterized by 1H NMR and 13C NMR (DMSO-d6) as well as by HRMS (ESI+) (Figures S3–S6, and S9 in Supporting Information File 1). In the 1H NMR spectrum, two sets of singlets at 4.41 and 4.76 ppm (CH2) were attributed to the –O=C–CH2–O– groups of the E/Z isomers of

• experiments, parameters like temperature, shaking time and volume of uranyl solution used were kept constant. In a typical experiment, 20 mL of a 1 mM aqueous uranyl acetate solution was adjusted to the target pH and then added to solid PCP HA. The solution was shaken at a fixed temperature of 25 °C for 4 h

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

• , and was stable for days stored at −20 °C (stability determined by 1H NMR, Figures S1–S4 in Supporting Information File 1). For the conjugation of 9 to Au–NH2, an excess of 9 was used to drive the conjugation reaction to completion. Unreacted 9 was then removed by repeated washing with water and buffer

• complex. The probe was absent in side-view classes. Synthesis of CI-994 and the Au–(CI-994) conjugate. Conditions: a) Boc2O, NEt3, THF, 0 °C to rt, 19 h, 70%; b) 4-nitrobenzoyl chloride, DIPEA, DCM, 0 °C to rt, 16 h, 74%; (c) H2, 10% Pd/C, MeOH/THF 1:1, rt, 17 h, 95%; d) AcCl, NEt3, THF, 0 °C to rt, 21 h

• , 67%; e) TFA, DCM, 0 °C to rt, 20 h; (f) MP-carbonate resin, MeOH, rt, 3 h, 95%; g) benzyl bromide, 1,4-dioxane/DMF 1:1, 90 °C, 19 h, 45%; h) 3, 5, HATU, DIPEA, DMF, 0 °C to rt, 40 h, 59%; i) H2, 10% Pd/C, THF, rt, 19 h, 99%; j) N-hydroxysuccinimide, EDC, DMF, 0 °C to rt, 16 h, 90%; k) TFA, DCM, 0 °C

Recent advances in the stereoselective synthesis of distal biaxially chiral molecules

• Fanxing Zhou,
• Chen Zhang,
• Lingyu Sun,
• Yiyun Fang,
• Siming Zheng,
• Lina Hu,
• Mengyang Shen,
• Zhen Zhao,
• Wei Xu,
• Yunqiang Sun and
• Zi-Qiang Rong

Beilstein J. Org. Chem. 2026, 22, 461–479, doi:10.3762/bjoc.22.34

• [2 + 2 + 2] cycloaddition reaction between α,ω-diynes 1 and monoalkynes 2, providing an alternative to traditional asymmetric coupling strategies for the synthesis of C2-symmetric biaryl chiral compounds (Scheme 1a) [40]. They further demonstrated the feasibility of constructing N-, O-, and C

• for the synthesis of remote biaryl scaffolds bearing both N–N and N–C chiral axes, using benzamides 27 and alkynylindoles 28 as substrates (Scheme 7) [48]. During an extensive investigation of reaction conditions and substrate scope they also were able to synthesize various diaxially chiral N–N and C

• –C derivatives through reaction of 1-alkynylnaphthalenes with benzamides. In this context they observed that the stereoselectivity of the alkyne insertion could be tuned by solvent effects, particularly with hexafluoroisopropanol, which induced inversion of the C–C axial configuration (not shown). In

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

• isomeric benzo[c]acridine. The structural reassignment of compound 968 will aid the medicinal chemistry development of this important compound. Keywords: cancer metabolism; compound 968; glutaminase; Introduction Cancer cells often show a strong reliance on glutamine uptake and metabolism [1][2

• . Compound 968 is a benzo[c]phenanthridine, made by a three-component cyclocondensation reaction between the 1,3 diketone dimedone, the aryl aldehyde 3-bromo-4-dimethylaminobenzaldehyde, and 2-naphthylamine. This reaction producing the benzo[c]phenanthridine core was first reported in the late 1960s [23][24

Concept-driven strategies in target-oriented synthesis

• David Yu-Kai Chen,
• Chao Li and
• Yefeng Tang

Beilstein J. Org. Chem. 2026, 22, 451–454, doi:10.3762/bjoc.22.32

• A (review, Mingji Dai and co-worker), ryania diterpenoids (review, Jin-Bao Qiao, Yu-Ming Zhao and co-worker), illisimonin A (review, Ming Yang and co-worker)]; and (iii) methodology towards target-oriented synthesis [oxidative dearomatization (simonsol C, Hong-Bo Qin et al.), reductive

• radical cyclization (prostaglandin D2 metabolite, Jun Huang et al.), reductive cyclization cascade (aglacin B, Jina Xiao, Yu Peng et al.), electrochemical cyclization (review, Bin Li, H. N. C. Wong, Xiao-Shui Peng et al.), photochemical reactions (review, Shao-Min Fu, Bo Liu et al.), carbene insertion

A facile and practical method for the synthesis of trans-(±)-taxifolin and its derivatives via Darzens reaction

• Bo Peng,
• Panpan Yang,
• Maaz Khan,
• Xiaotong Lin,
• Jiang Wu,
• Peng Fu and
• Qingqing Wu

Beilstein J. Org. Chem. 2026, 22, 443–450, doi:10.3762/bjoc.22.31

• give protected acetophenone 1 in an excellent yield of 78%. Next, the reaction conditions for the following α-bromination of acetophenone 1 to intermediate 2 were screened (Table S1, Supporting Information File 1). The treatment of compound 1 with CuBr2 in EtOAc at either room temperature or 60 °C

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

• on the differences of the heteroatom and substituents on the (E)-alkene moiety [11][12]. The half-lives of the optical activity optt1/2 of 1aa (X = O, Y = H) and 1ba (X = NTs, Y = H) were 380 h and 56.7 h at 25 °C, respectively, indicating that the stereochemical stability of the oxygen-containing

• cycle is higher than that of the nitrogen cycle: optt1/2 is one order of magnitude longer. On the other hand, C6-methyl-substituted nitrogen cycle 1bb (X = NTs, Y = Me) exhibits highly dynamic planar chirality (optt1/2 = 0.6 h at 25 °C), indicating that a C6-substituent decreases the stereochemical

• -substituted oxa[7]orthocyclophenes could exhibit reasonable dynamic planar chirality with optt1/2 approximately 10 h at 25 °C, which is dynamic but can be handled maintaining the enantiomeric purity in careful experimental operations [13][14]. In this study, we have designed, synthesized, and analyzed C6

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

• conserved 3-(4-(tert-butyl)phenoxy)propyl function at the imide nitrogen. The resultant naphthalimide–organylselanyl conjugates, NAP-SePh and NAP-Se(n-Oct), were characterised using various spectroscopic techniques, including FTIR, ¹H, ¹³C, ⁷⁷Se NMR and high-resolution mass spectrometry (HRMS). NAP-SePh was

• compounds, making it a viable alternative for introducing long alkyl chains into selenium-containing systems towards lysosomal membrane permeability (vide supra) [42][43][44]. After synthesis, compounds 7 and 8 were thoroughly characterised using multinuclear NMR spectroscopy ¹H, ¹³C, and ⁷⁷Se NMR

• 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

• mixture, from 0 °C → rt, overnight) the nitration of calixarene 6 resulted in a mixture of exhaustively nitrated product 11, partially nitrated calixarenes having nitro and tert-butyl groups at the wide rims, and a large amount of other calixarene side product(s) having broadened and non-interpretable NMR

• homogeneous reduction using tin(II) chloride in ethanol was used after fine-tuning of the published reaction conditions [9]: the reduction was conducted by gentle heating of a mixture of calixarene 11, SnCl2·2H2O, aqueous HCl and ethanol at 70 °C (instead of prolonged boiling of the reaction mixture) in a

• desilylated product in the case of calixarene 22) remained in the reaction mixtures even after their stirring at room temperature for 72 h. In the case of calixarene 22, heating of the mixture at 50 °C for 48 h was enough to complete the process and p-aminocalix[4]arene 25 having two propargyl groups at 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

• spectroscopy, LC–MS and elemental analysis (Supporting Information File 1, Figures S1–S36). The IR spectra of compounds 1–5 showed the presence of NH absorption bands in the range 3381–2936 cm−1, OH at 3396 cm−1 (compound 9), and C=O at 1601–1610 cm−1 (compounds 6-8). Cytotoxic potency of the compounds 1–9

• -chlorooxazolo[4,5-d]pyrimidines IІ in 30 mL of anhydrous dioxane was added dropwise to a solution of 0.03 mol of the appropriate amine and 0.01 mol of triethylamine in 20 mL of anhydrous dioxane over 0.5 h. The reaction mixture was heated for 5 h at 100–110 °C and left for 12 h at 20–25 °C. The solvent was

• seeded into 96-well microplates at 2 × 104 cells/well. After overnight incubation of cells at 37 °C in a humidified atmosphere containing 5% CO2, the culture medium was removed and replaced with a 100 μL of freshly prepared solution of compounds diluted with the growth medium supplemented with 10% FBS

Dialkylaminoalkylation of β-ketosulfones via ring-opening of 3-sulfonylpyrrolidines

• Evgeny M. Buev,
• Alexander V. Pavlushin,
• Vladimir S. Moshkin and
• Vyacheslav Y. Sosnovskikh

Beilstein J. Org. Chem. 2026, 22, 383–389, doi:10.3762/bjoc.22.26

• the fast increase of the molecular complexity, remains significant. Unlike the classical aminoethylation of nucleophilic compounds [28][29], Batey et al. recently developed a two-step approach consisted in addition of terminal ynimides I to various electrophiles with subsequent reduction of the C≡C

• decided to increase the reaction temperature. Thus, refluxing the reagents in the PhMe/MTBE mixture (v/v 17/3, approximately 100 °C) for 4 h led to complete conversion of the ketosulfone and formation of 3-phenylsulfonyl-3-benzoyl-N-methylpyrrolidine (2a) in almost quantitative yield. Despite that [3 + 2

• cesium carbonate at 25 °C for 96 h provided higher yield (Table 1, entry 2, 70%). However, heating this mixture at 65 °C for 24 h in a sealed vial gave pure desired 4-methoxy-N,N-dimethyl-3-(phenylsulfonyl)butan-1-amine (4a) in 90% yield and 83% overall yield starting from ketosulfone 1a (Table 1, entry

Electrosynthetic access to unsymmetrical oxaza[8]helicenes with high chiral stability and strong circularly polarized luminescence (CPL)

• Tin Zar Aye,
• Rubal Sharma,
• Muthu Karuppasamy,
• Daiya Suzuki,
• Haruka Nakajima,
• Yoshitane Imai,
• Mitsuhiro Arisawa,
• Mohamed S. H. Salem and
• Shinobu Takizawa

Beilstein J. Org. Chem. 2026, 22, 372–382, doi:10.3762/bjoc.22.25

• barriers of 5a and 5b translate into excellent configurational robustness, as demonstrated by the absence of detectable enantiomerization when solutions of (M)-5a were heated at 130 °C for 2.5 h. Optical properties of oxaza[8]helicenes Photophysical features The absorption and emission spectra of oxaza[8

• enantiomers at lower temperature and samples were stored at −20 °C before their chiroptical responses were evaluated. The optical purities of (P/M)-6a and (P/M)-6b measured samples were confirmed to be >97% ee, confirming the reliability of our results. However, this low enantiomerization barriers of oxaza[7

• structures). Aromaticity of oxaza[8]helicenes: (A) NICS(0)zz and NICS(1)zz values of 5a and 5b calculated at MN15/6-311G(2d,p)/SMD=chloroform level of theory; (B) ACID plots calculated at the B3LYP/6-311G(d,p) level of theory (isosurface value: 0.05). (P/M) Enantiomerization process of 5a (A), 5b (B), 6a (C

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

• , bioactive molecules, and advanced materials. However, its exceptional resonance stabilization renders the C–N bond highly inert, posing a persistent synthetic challenge for its transformation. While twisted amides with distorted C–N bonds have offered useful reactivity enhancements, the selective activation

• of conventional, non-activated amides remains far more difficult. This review summarizes recent advances over the past decade in the activation and cleavage of non-activated amide C–N bonds for their conversion into diverse carboxylic acid derivatives. Key strategies covered include transition-metal

• a major objective in contemporary synthetic chemistry [12][13][14][15][16]. Despite their ubiquity, amides are notoriously unreactive toward classical acyl-substitution pathways. This inertness arises from a strong amidic resonance, which confers partial C=N double-bond character and a planar

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

• framework is impossible is one of the ways to improve properties of ORCA. Feasibility of the synthesis of rigid 3b,4,5,6,6a,7-hexahydropyrrolo[2',3':3,4]pyrrolo[1,2-c][1,2,3]triazole and 3b,4,5,6,6a,7-hexahydropyrrolo[2',3':3,4]pyrrolo[1,2-b]pyrazole ring systems with incorporated nitroxide moiety from 2

• Huisgen cycloaddition or via one-pot Michael addition–cyclocondensation reaction with hydrazine with subsequent intramolecular alkylation of the resulting pyrazoles. Results and Discussion Synthesis We have earlier reported on the synthesis of 2-alkynylpyrrolidine-1-oxyls 2a–c via addition of the

• nitroxides 2d–f, the samples of the radicals were reduced to the corresponding diamagnetic amines using a Zn/CF3COOH system in CD3OD at 63 °C, according to a literature protocol [23] and the 1H NMR spectra were recorded. The spectra showed similarity to those of previously described for radicals 2a–c [20

Ring contraction and ring expansion reactions in terpenoid biosynthesis and their application to total synthesis

• Nicolas Kratena,
• Nicolas Heinzig and
• Peter Gärtner

Beilstein J. Org. Chem. 2026, 22, 289–343, doi:10.3762/bjoc.22.21

• biosynthesis, when the oxidation state of the terpenoids is being adjusted [28][29][30][31][32][33][34][35][36]. Starting with an already substantial number of these common polycyclic frameworks and adding the almost unlimited variability for oxidative enzymatic C–H functionalisation, it is not surprising that

• included [48][49]. These enzymes exhibit distinctly different Fe-containing active sites, typically consisting of two histidines, a carboxylate ligand (e.g., aspartate) and, of course, the ketoglutarate which is bound both via the C-2 ketone and C-1 carboxylate to form 1 (Scheme 1C). Upon its coordination

• carbocation 23d. A triple asynchronous shift occurs, consisting of C12-alkyl (13→16), 1,3-hydride (12→13), and C-13 alkyl shift (16→12). This complex, concerted process directly converts the tertiary cation 23c into the tertiary cation 23d completely avoiding secondary cations and resulting in another 5→6

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

• of the target products. We observed that murexide formation decreased when the reaction was carried out in anhydrous 1,4-dioxane under an inert atmosphere at 100 °C. When using dry acetonitrile as a solvent, the reaction yields were lower, so we decided to use a higher-boiling solvent – 1,4-dioxane

• Awad I. Said et al. [54]. The cycloaddition reactions were performed in sealed tubes under an inert atmosphere at 100 °C in anhydrous 1,4-dioxane with constant stirring for 6–16 h. Reaction progress was monitored by TLC (CH2Cl2/MeOH 25:1) and the spirobarbiturates were isolated from the reaction

• -adducts 4a–e, the carbon signals of ring A (Figure 1) appear at δC 44.8–45.0 ppm (CH21), 27.3 ppm (CH22), and 25.2 ppm (CH23). Ring B carbons resonate at δC 67.7–67.8 ppm (CH4), 46.3–46.4 ppm (CH5), and 58.2–58.3 ppm (CH6). The carbonyl carbons of ring C and the barbiturate ring appear at δC 150.0, 169.3

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

• disrupting the aromatic core, such as electrophilic and nucleophilic aromatic substitutions, transition metal-catalyzed cross-couplings [11], and C–H functionalizations [12]. Taken together with their natural abundance, these transformations have established arenes and heteroarenes as versatile synthetic

• hydrogenation of the aromatic core of highly substituted benzocyclobutenes using simple Pd/C under ambient conditions [38]. The pronounced substituent effects on the hydrogenation rate highlight the key role of small-ring strain in this generally challenging transformation. Complementary to these strictly

• emphasized heteroatom-driven reactions in which metal coordination enhances the natural polarization of the molecule, primarily by disrupting its aromaticity. For example, a π-base preferentially binds to the C(2) and C(3) positions of monosubstituted arenes, maintaining linear conjugation between the

A mild and atom-efficient four-component cascade strategy for the construction of biologically relevant 4-hydroxyquinolin-2(1H)-one derivatives

• Dmitrii A. Grishin,
• Kseniia I. Sharkovskaia,
• Ilya G. Kolmakov,
• Daria A. Ipatova,
• Rostislav A. Petrov,
• Nikolai D. Dagaev,
• Dmitry A. Skvortsov,
• Maria G. Khrenova,
• Valeriy V. Andreychev,
• Sergei A. Evteev,
• Yan A. Ivanenkov,
• Roman L. Antipin,
• Olga А. Dontsova and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2026, 22, 244–256, doi:10.3762/bjoc.22.18

• -hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)-3-phenylpropanoic acid have not, to the best of our knowledge, been previously described. Structurally related compounds, such as 4-aryl-4,6-dihydro-2H-pyrano[3,2-c]quinoline-2,5(3H)-diones, have been reported only in a few cases, typically via multicomponent

• , cyanoacrylates, and others. The second approach consists of the Michael 1,4-addition of the corresponding acetate or malonate anion to 3-arylidenequinolinedione. Both strategies were evaluated in subsequent studies. To implement these routes, 6-halogen-4-hydroxyquinoline-2-ones 2a–c were prepared. The synthesis

• (Scheme 3) involved the optimization of a two-step procedure reported previously for their preparation from corresponding anilines and malonic ester [40][41][42][43]. The intermediate N1,N3-bis(4-halogenophenyl)malonamides 1a–c were synthesized from 4-halogen-substituted anilines and diethyl malonate in

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

• conformational stability. High-level DLPNO-CCSD(T)/CBS calculations revealed that type-I conformers – those maximizing gauche interactions between C–F and C–N bonds – dominate the equilibrium population, confirming the presence of the fluorine gauche effect. natural bond orbital (NBO) analysis showed that this

• 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

• this framework, DFMO is expected to display the gauche effect when type-I structures dominate, because the polar C–N bond forms two gauche interactions with the polar C–F bonds. High-level DLPNO-CCSD(T)/CBS calculations support this expectation: the four lowest-energy structures are type I and together