Palladium-catalyzed benzocyclization reactions of quinoline-2-carboxamides via sequential C–H/N–H functionalization

• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2026, 22, 905–914, doi:10.3762/bjoc.22.71

• efficient access to chemodivergent products. The developed reaction protocol is expected to be applicable to the synthesis of functional materials and bioactive molecules. Nuclear Overhauser effect (NOE) correlations in products (a) 3ab, (b) 3ac, (c) 3ad, (d) 3aj, and (e) 3ak. Various transition-metal

Cascade transformation of 2-(diazoacetyl)-2H-azirines to 2-aroyl-3-hydroxy-1H-pyrroles via condensation with aromatic aldehydes

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2026, 22, 897–904, doi:10.3762/bjoc.22.70

• ) exhibiting a lower relative Gibbs free energy than the starting compounds. According to the calculations, the reaction of azirine 1a and benzaldehyde 2c results in the formation of two diastereomers, (RR,SR)- and (RR,RR)-A, which can undergo a conformational transition to intermediates (RR,SR)- and (RR,RR)-B

• , which are capable of cyclization. The cyclization of (RR,SR)-B leads to the (1RR,3SR,6RR)-Pha-C isomer with the Ph group from benzaldehyde in the axial position, which readily transforms into the more stable (1RR,3SR,6RR)-Phe-C isomer with equatorial Ph group as a result of inversion of the 6-membered

• ring. The intermediate (RR,RR)-B immediately yields a more stable conformer with the Ph group from benzaldehyde in the equatorial position (1RR,3RR,6RR)-Phe-C, but the equilibrium as a whole is shifted towards the most stable isomer (1RR,3SR,6RR)-Phe-C isomer. According to the calculation, the

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

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

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

• anti-form of 6a. With mode B, the π–π stacking between benzophenone-imine 2a and the phenoxylmethyl group in 5a may enhance the ratio of this attack to produce the syn-form of 6a as major product. A mechanism for this highly enantioselective Michael addition between 2a and 5a was proposed based on

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

• enhance the formation of transition state B. The highly diastereomic ratio of 6a in syn-form may be generated from transition state B. The formation of intermediate C is the rate-limiting step. When intermediate C is formed, the protonation happened rapidly to afford 6a in high enantioselectivity. The

Diastereodivergent electrophilic trapping of α-boryl lithium derivatives

• Tereza Pavlíčková,
• Noam Orbach and
• Ilan Marek

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

• delocalization leads to the formation of a partial π C–B bond (Scheme 1) [1][2], which provides a unique stabilization to the carbanionic center and affects its reactivity towards electrophiles. In recent years, α-boryl carbanions have attracted significant attention as highly versatile intermediates capable of

• calculations, this model assumes initial coordination of both the vinyl group and the Bpin moiety to the lithium counterion. Within this constrained geometry, when R2 = H, R3 = alkyl, the diastereocontrol is then governed by the relative steric interactions present in these two possible conformers B and C

• . This conformational constraint rigidifies the system through formation of a pseudo-ring, leading to potential gauche interactions between R1 and R3 in conformer B (Scheme 5). In conformer C, however, substituents R1 and R3 are further apart, which expose a free diastereotopic face above the plane of

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

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

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

• , with applications in ADC development, radiolabelling and ROS/Ca2+ imaging (Scheme 9a) [86][87][88][89][90][91]. Methionine can also be modified via sulfonium conjugates using hypervalent iodine (23, Scheme 9b) [92] or photoredox approaches (24a/b, Scheme 9c) [93]. Histidine has been targeted using

• key amines on insulin, including the N-terminal glycine of chain A, the N-terminal phenylalanine of chain B and the ε-amino group of lysine B29. Using a colony picker and UPLC analysis, mutations were introduced within the binding pocket (to enhance localised recognition of insulin) and at distal

• (1), b) reductive amination by sodium cyanoborohydride, c) native chemical ligation, d) cysteine-reactive 2-cyanobenzothiazole 2 and e) formylphenylboronic acid 3 (FPBA) reacting with N-terminal cysteine. Introduction of carbonyl functionality at protein N-termini via a) oxidation by periodate, b

The trans-influence in gold chemistry from a catalytic perspective

• Manfred Bochmann

Beilstein J. Org. Chem. 2026, 22, 838–856, doi:10.3762/bjoc.22.66

• of Pt–CO. Bonding analysis of these CO complexes indicates mainly σ-donation but little back-donation, with donation/back-donation (d/b) ratios much larger than in the comparable Pt(II) complex [(C^N^N)Pt–CO]+. DFT studies found no evidence for π-bonding contributions to the Au–CO bond in the highest

• be underestimated. For example, cleavage of one of the Au–phenyl bonds in A (Scheme 2) with a strong acid provides access to the gold borane and silane σ-complexes [(C^N–CH)Au(C6F5)(H–X)]+, X = B(O2C2Me4) or SiEt3 (Scheme 3) [32]. In the presence of traces of moisture, the Au(III)+ Lewis acidity may

• the range of dianionic C^C chelates to dicarboranyls highlights the effects of electronic characteristics. For example, while the removal of a trifluoroacetate ligand by B(C6F5)3 can usually be relied upon to quantitatively create a vacant coordination site [27][28][29], in the case of 7 this method

Unsymmetrical sulfoxides with sterically hindered catechol fragment: synthesis, structure, electrochemical properties, and antiradical activity

• Daria A. Burmistrova,
• Vasiliy A. Fokin,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Maxim V. Arsenyev,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2026, 22, 828–837, doi:10.3762/bjoc.22.65

• ), the second redox stage splits into two steps. The first yields a relatively stable cation radical (Ic/Ia = 0.45–0.50) (Scheme 2, path b), while the subsequent redox transition occurs at higher potentials (2.03–2.06 V) (Figure 3). In the case of catechols 7 and 7a, the second oxidation peak appears in

• antioxidants, stimuli-responsive materials, and functional ligands for metal complexes with tailored electronic properties. Molecular structures of 1a (a), 4a (b), 5a (c), 6a (d), 7a (e) (solvent molecules and fragment disordering are omitted; for 4a and 5a, only one independent molecule is shown). CV curves

• ). Synthesis of catechol-contained thioethers 1–7 and sulfoxides 1a–7a. Proposed mechanism of electrochemical transformations of catechol sulfoxides (path a – for 1a, 3a, 4a, 6a, and 7a; path b – for 2a and 5a). Proposed mechanism of the reduction of electrogenerated o-benzoquinone. Peak (Epox) potentials of 1

Synthesis and structural elucidation of a novel bis-spirooxindole from isatin and ethylenediamine

• Irene Moreno-Gutiérrez,
• Josefa L. López-Martínez,
• Sonia Berenguel-Gómez,
• Irene Torres-García,
• Duane Choquesillo-Lazarte,
• Manuel Muñoz-Dorado,
• Miriam Álvarez-Corral and
• Ignacio Rodríguez-García

Beilstein J. Org. Chem. 2026, 22, 813–820, doi:10.3762/bjoc.22.63

• -diamine ratio (Scheme 4a,b). When isatin was reacted with ethylenediamine in a 2:1 molar ratio in methanol, the expected diiminoisatin 24 was obtained in 66% yield. The ¹H NMR spectrum displayed a diagnostic singlet at δ 4.45 ppm (4H) corresponding to the two =NCH₂ groups, together with the characteristic

• group C2/c (no. 15), a = 16.0100(5) Å, b = 8.5258(4) Å, c = 16.6847(5) Å, β = 105.815(2)°, V = 2191.22(14) Å3, Z = 4, T = 298(2) K, μ(Cu Kα) = 0.712 mm−1, Dcalc = 1.244 g/cm3, 11324 reflections measured (11.488° ≤ 2Θ ≤ 136.964°), 2001 unique (Rint = 0.0404, Rsigma = 0.0308) which were used in all

• ), MeOH, reflux, 5 h, 66%; (b) ethylenediamine (2 equiv), EtOH, reflux, 6 h, 67%; (c) 2 equiv NaBH4 (58%) or NaBH3CN (76%), reflux, MeOH. Proposed mechanism for the formation of 25. Synthesis of 30 from 5-methylisatin (29). Supporting Information Supporting Information File 32: Copies of IR, NMR and MS

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

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

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

• diazafluorene fragments along (a + b) (Figure 2b). The stacks of molecules are linked together via π···π and C–H···π interactions between pyridine fragments (Figure 2c). To further evaluate the complexation behavior of 4,5-DPDAF we co-crystallized the compound with ZnCl2 resulting in a unique complex (Zn–4,5

• CH2Cl2 solution and b) optical absorption spectra of 4,5-DPDAF and 1,8-DPDAF in THF. Molecular structure, atom and cycle numbering of 4,5-DPDAF (a) and Zn-4,5-DPDAF (d) with anisotropic displacement ellipsoids drawn at a 50% probability level; crystal structure fragments of 4,5-DPDAF with π-stacking (b

Synthetic study of vic-bromination of diarylacetylenes, easy purification and separation

• Akane Togo,
• Hiyono Suzuki,
• Yuto Akai,
• Makoto Matsumoto,
• Yoshinori Suzuma,
• Hidehiko Kodama and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2026, 22, 795–802, doi:10.3762/bjoc.22.61

• can react with 1a to form intermediate A. A reacts with Br− to give E-2a. Another possibility is the reaction of NBS and FeBr3 gives coordinated intermediate B, which can react with 1a to give A, leading to the formation of E-2a [21][22]. Both pathways may be mixed together. One reason why E and Z

• ; HRMS (ESI) m/z: [M + Na]+ calcd for C14H11Br2, 336.9222; found, 336.9215. Selected and previous reports for bromination of diphenylacetylenes (a–c), and this work (d). Gram-scale synthesis of (a), and control experiments of (b), (c) and (d). n.r. = no reaction. Plausible reaction mechanism of the

Halogenated azobenzene acrylates: from efficient solution photoswitching to stable solid-state photochromic materials

• Martina Vachtlová,
• Michaela Fecková,
• Vítězslav Zima,
• Jan Podlesný,
• Milan Klikar,
• Oldřich Pytela,
• Patrik Pařík,
• Jakub Opršal,
• Eliška Juhaňáková,
• Veronika Chrtová and
• Filip Bureš

Beilstein J. Org. Chem. 2026, 22, 782–794, doi:10.3762/bjoc.22.60

• reverse reduction of the chemically modified oxidized form was recorded as a broad peak at significant undervoltage, especially for derivatives 1a–b and 1d–e. The electrochemical data suggest that the first oxidation and the first reduction processes are associated with different parts of the molecule

• ) and DFT-calculated (red for E-isomers and blue for Z-isomers) energies EHOMO/LUMO for azobenzenes 1a–f. A) Experimentally measured UV–vis absorption spectra of the monosubstituted azobenzenes 1a, c and e at c = 4 × 10−5 M in DCE corresponding to the dark-adapted PSS = pure E-isomers. B) Calculated UV

• –vis absorption spectra of the monosubstituted Z-azobenzenes 1a, c and e. A) Experimentally measured UV–vis absorption spectra of the azobenzenes 1c and 1d at c = 4 × 10−5 M in DCE corresponding to the dark-adapted PSS = pure E-isomers. B) Calculated UV–vis absorption spectra of the azobenzenes 1c and

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

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

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

• , selonsertib, Z8, Z30, or the combination of GW4064 and selonsertib for 2 h prior to OA stimulation (600 μM). (A) Representative Oil Red O staining images (40×). (B) Quantification of staining intensity by ImageJ. Data are presented as mean ± SD (n = 3). Statistical significance was analyzed by one-way ANOVA

• FXR/ASK1 modulation strategy for MASH. Synthesis of compound 2. Conditions: (a) NH2OH·HCl, NaOH, EtOH/H2O, 70 °C, 12 h; (b) NCS, DMF, 40 °C, 2 h; (c) methyl 3-cyclopropyl-3-oxopropanoate, triethylamine, EtOH, rt, 12 h, 64% yield; (d) LiAlH4, THF, 0 °C, 2 h, 68% yield; (e) PBr3, DCM, 0 °C, 12 h, 79

• % yield. Synthesis of compounds IXa–d. Conditions: (a) N2H4·H2O, MeOH, rt, 12 h; (b) DMF–DMA, 80 °C, 12 h; (c) amines (for IXa,c,d) or (R)-alanine methyl ester (for IXb), AcOH, MeCN, 90 °C, 16 h, 66–80% yield; (d) absolute stereochemistry is R. Synthesis of compounds Z1–15. Conditions: (a) K2CO3, KI, MeCN

Preparation of 3-(alkylamino)imidazo[1,2-a]pyridine-2-carbaldehydes via Kornblum oxidation and unexpected ring-opening reactions of the corresponding alcohols under oxidative conditions

• Sandile J. Mkhize,
• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2026, 22, 763–770, doi:10.3762/bjoc.22.58

• under different conditions. Preparation of methyl esters 13 versus unsubstituted derivatives 12 under various conditions. Method A: 0.1 equiv HClO4, MeOH, rt (≈350 mg aminopyridine); method B: 1. glyoxylic acid monohydrate, 0.2 equiv HClO4, MeOH, reflux, 2 h; 2. aminopyridine 9, cyclohexyl isocyanide 10

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

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

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

• A ring of A/B trans-fused (5α steroids). This is the consequence of the steric hindrance imposed by the 19-methyl group, which prevents OsO4 from approaching the top face of the A ring, and thereby favoring the reaction from the lower face of the double bond [29][33][34]. The structural

• new BR analogs 17–22, from 23,24-bisnor-5-cholenic acid 3β-acetate (15). Conditions: a) p-R-PhCOCl/CH2Cl2/py, DMAP, rt, 2 h, 96.7%, 78.0%, 91.2%, 95.3%, 95.6%, and 93.6% yields for 23–28, respectively. b) DHQD-CLB, CH3SO2NH2, K2CO3, K3[Fe(CN)6], OsO4, t-BuOH/H2O (1:1 v/v), rt, 36 h, 77.8%, 67.9%, 65.8

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

• iminoester 1 with tert-butyl acrylic acid ester 4 occurs first. This is followed by condensation of pyrrolidine 9 with cinnamic aldehyde (10) to form azomethine ylide B, which enters into a second diastereoselective 1,3-DC with various electrophilic alkenes. The authors used acrylic acid esters, vinylphenyl

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

• . These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via http://www.ccdc.cam.ac.uk/data_request/cif. Crystal data for (+)-eudesmin (3) C22H26O6, M = 386.43, T = 100.0 K, 1.54184 Å, monoclinic, space group P21, a = 11.42420(10) Å, b = 32.78820(10) Å, c = 11.53130(10

• bovine serum (FBS), in triplicates. The bottom wells contained 700 µL of DMEM (10% FBS). This was incubated for 24 h at 37 °C with 5% CO2. Vehicle control (positive control) was the solvent DMSO, in which all compounds were dissolved, plus cells. The final concentration of DMSO was 0.01%. (B) The U251MG

• DMEM (0% FBS) in triplicates. The bottom wells contained 700 µL of DMEM (10% FBS). This was incubated for 24 h at 37 °C with 5% CO2. Vehicle control (positive control) was the solvent DMSO, in which all compounds were dissolved, plus cells. The final concentration of DMSO was 0.01%. (B) The % invasion

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

• ketone in a later step for the synthesis of 1. The 5-hydroxy group in 11 was then protected as a TBS ether to give 12 in 96% yield. However, direct deoxygenation of the 13-ketone of 12 was not fruitful in our hands [58][59][60]. We then converted enone 12 to the allylic alcohols 13a/b as two

• the benzoate ester for reductive deoxygenation were not successful [63], and 13a/b decomposed in the esterification step. We have finally found that the 13-hydroxy group could be smoothly removed by the methyl oxalyl ester deoxygenation method [64][65]. Thus, 13a/b were esterified with methyl

• chlorooxoacetate to give 14a/b in 84% yield, which were subjected to the radical deoxygenation conditions (AIBN, n-Bu3SnH) for 13-hydroxy removal, affording two deoxygenated products that were difficult to be separated from each other. Without further purification, the obtained mixture was treated with tetra-n

Using generative AI to transform peptide hits into small molecule leads

• Joshua Mills and
• Yu Heng Lau

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

• , based on training with a supplied dataset. B) Models can use different chemical representations as inputs, such as SMILES strings, point clouds, or molecular graphs. Selected examples of structure-based AI/ML tools for potential end-to-end coverage of the peptide to small molecule pipeline. Tools are

Photoorganocatalytic trifluoromethylation of (het)arenes in green conditions

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

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

• , including rhodamine B, rhodamine 6G, eosin Y, riboflavin, methylene blue, THPP (tetrahydroxyphenylporphyrin), Birch O-PC™ C0103 (benzo[ghi]perylene monoimide) [28], 4CzTPN (tetracarbozalylterephthalonitrile), and 4CzIPN (tetracarbozalylisophthalonitrile), did not afford the desired product (Table 2, entry 1

Advantages of PROTACs in achieving selective degradation of homologous protein families

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

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

• the VH032 ligand. Through systematic optimization of linker lengths, it was found that the molecule achieved optimal activity when the linker a consisted of six methylene groups and linker b consisted of three methylene groups. The resulting products 37 exhibited DC50 values of 7.7 nM and 5.0 nM for

• structure revealed that linker b forms hydrophobic interactions with the ZA loop of BRD4BD2 and stabilizes the PPI interface via a conserved salt-bridge network, while linker a acts as a "hinge" to bring the two proteins into proximity. This study systematically elucidated how macrocyclic linker length and

Hydrogen production from formic acid catalyzed by NHC–Cu complexes

• Orlando Santoro and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2026, 22, 620–627, doi:10.3762/bjoc.22.48

• reached a plateau within minutes (Figure 2a and b). Such a value corresponded to the production of ca. 1.5 equivalents of gas (see Supporting Information File 1, section 4). Notably, when [Cu(Ot-Bu)(IMes)] (2a) was employed, the reaction proceeded slowly (Figure 2c). This can be due to the faster

• : formic acid (0.5 mmol, 1 equiv), toluene 2 mL, 3 h. 1a 10 mol %, PhSiH3 (1 equiv), 25 °C (a); 1c 10 mol %, PhSiH3 (1 equiv), 25 °C (b); 2a 10 mol %, PhSiH3 (1 equiv), 25 °C (c); 1a 1 mol %, PhSiH3 (1 equiv), 25 °C (d); 1a 0.1 mol %, PhSiH3 (1 equiv), 40 °C (e). Decomposition of FA catalyzed by NHC–Cu

• complexes in the presence of different silanes. Reaction conditions: formic acid (0.5 mmol, 1 equiv), silane (1 equiv), toluene 2 mL, 1a (10 mol %), 25 °C, 1 h. PhSiH3 (a); Me(EtO)2SiH (b); (EtO)3SiH (c). Hypothetical mechanism for FA decomposition via decarboxylation of NHC–Cu–formato species. Isotopic

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

• on 1 (PDB: 5CU4) and S13 (PDB: 9TTA; please see Supporting Information File 1, section 1.4.18 for the full structure). B) Crystal structure of S13. The map is Fo-Fc contoured at 1.5 σ. C) Isothermal titration calorimetry (ITC) reveals the suitable position for linker vector to attach the E3 ligases

• -diisopropylethylamine; DME = 1,2-dimethoxyethane; DMF = dimethylformamide; HOBt = 1-hydroxybenzotriazole; TFA = trifluoroacetic acid. (A) Synthesis of final VHL PROTACs; (B) Synthesis of final CRBN PROTACs. Abbreviations: Boc = tert-butoxycarbonyl; CRBN = cereblon; DIPEA = N,N-diisopropylethylamine; DMF

• grateful to the Czech Science Foundation (GA CR 22-07138O) for their financial support. A. R. Sokhal is grateful to the Gates Cambridge Trust for their financial support (https://www.gatescambridge.org). The Spring lab acknowledges support from the EPSRC, BBSRC, MRC, and Cystic Fibrosis Trust UK. B. C

Computational prediction of C–H hydricities and their use in predicting the regioselectivity of electron-rich C–H functionalisation reactions

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2026, 22, 603–610, doi:10.3762/bjoc.22.46

• hydride transfer reaction, ; see Equation 1. For each set of C–H sites in a molecule, we determine the minimum hydricity (). Hereafter, we assume a linear relationship between the experimental hydricity and as this assumption allows us to derive the empirical constants a and b and correct any systematic

• errors, such as the hydride (H−) ion; see Equation 2, where ΔG° is replaced by . After retrieving the empirical constants a and b, we can determine the QM-computed hydricities for all C–H sites using Equation 2: Because G°(H−)solv is constant across substrates, it is absorbed into the fitted intercept b

• on the entire training set and evaluate it on the test set, selecting the best-performing model. Results and Discussion Computing C–H hydricities In section “Quantum chemistry-based workflow”, we determine the empirical values a and b in Equation 2. For each set of C–H sites in a molecule, we extract

Regioselective approach to 5-arylsulfonylisoxazoles and their antimicrobial activity

• Artem S. Sazonov,
• Dmitry A. Vasilenko,
• Denis V. Porfiriev,
• Yuri K. Grishin,
• Rimma A. Gazzaeva,
• Alisa P. Chernyshova,
• Maxim A. Kryakvin,
• Anna A. Baranova,
• Vera A. Alferova and
• Elena B. Averina

Beilstein J. Org. Chem. 2026, 22, 592–602, doi:10.3762/bjoc.22.45

• Artem S. Sazonov Dmitry A. Vasilenko Denis V. Porfiriev Yuri K. Grishin Rimma A. Gazzaeva Alisa P. Chernyshova Maxim A. Kryakvin Anna A. Baranova Vera A. Alferova Elena B. Averina Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1-3, Moscow 119991, Russian Federation

• 5-sulfonylisoxazoles (Scheme 1, approaches A, B, C). As shown in Scheme 1, nitrile oxides are generated in situ by oxidation of aldoximes with chloramine T (approach A) or by dehydrohalogenation of the corresponding oxime halide under basic conditions (approaches B and C). Subsequently, the nitrile

• 4-unsubstituted isoxazoles with various aryl substituents in position 3 [24][25] (approach B). One example describes the Ru-catalyzed reaction of nitrile oxide with alkynyl sulfone providing 5-sulfonylisoxazole with high regioselectivity [26] (approach C). Despite the widespread application of

Design and synthesis of an erdafitinib-based selective FGFR2 degrader

• Yumeng Jin,
• Shidong Wang,
• Sihan Pan,
• Shuqi Huang,
• Weichen Zhou,
• Xiaohao Huang,
• Lei Zheng and
• Lingfeng Chen

Beilstein J. Org. Chem. 2026, 22, 583–591, doi:10.3762/bjoc.22.44

• ]. b) The FGFR2 design strategy. a) Representative western blots evaluating the total FGFR2 levels in KATO III cells following treatment using the indicated PROTAC. b) Time-course of FGFR2 degradation. c) Chemical structure of LC-JD-6. d,) Dose-course of FGFR2 degradation. e) Cell viability in KATO III

• and HEK293T cells. a) FGFR1, FGFR2, FGFR3, and FGFR4 levels in cells after treatment. b) The mechanism of PROTAC. It was created in BioRender (Chen, Lingfeng https://BioRender.com/7td2yot). This content is not subject to CC BY 4.0. c) Cellular localization of FGFR2 after treatment with LC-JD-6

• . Synthesis of PROTACs towards FGFR2. Reagents and conditions: (a) K2CO3, Pd (dppf)Cl2, 1,4-dioxane/H2O 4:1, 100 °C, 5 h; (b) 3,5-dimethoxyaniline, Pd2(dba)3, BINAP, Cs2CO3, toluene, 100 °C, 12 h; (c) (2-bromoethoxy)-tert-butyldimethylsilane, NaH, DMF, rt, 12 h; (d) tetrabutylammonium fluoride, THF rt, 12 h