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

• of proteins are linear polypeptide chains, possessing a single N- and C-terminus and hence presenting these regions as attractive targets for site-specific modification. Indeed, over 80% of protein termini are solvent-exposed and chemically accessible [5]. Notably, the N-terminal amine and C-terminal

• cysteine [15]. These intermediates enable downstream chemical conjugations such as Pictet–Spengler condensation [16][17][18] and Horner–Wadsworth–Emmons (HWE) olefination [19] (Scheme 2c). With respect to C-terminal modification, one of the earliest strategies involved the use of intein-mediated protein

• splicing to generate a C-terminal thioester from recombinantly expressed proteins [20][21][22]. One distinctive feature of the C-terminal carboxylate is its lower oxidation potential compared to the side chains of aspartate or glutamate, making it more amenable to selective redox-based modifications. This

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

• . This effect is probably more dominant in gold chemistry than in most other transition-metal complexes; it can on occasions appear even more important than the formal oxidation state and d-electron count. Tilset and co-workers have recently summarised the importance of the trans-influence in C^N

• electron-rich trialkylphosphines, increased the proportion of N-bonded thiocyanate [24]. More recently, Espinet and co-workers used solution microcalorimetry with in-situ generated HI to provide bond dissociation energy scales for the Au–C bonds in R–Au(PPh3) (R = Me, aryl or alkynyl), and further to

• determine the effect of ligands L in the protolysis of LAuPh, where reaction enthalpies were shown to decrease in the order P(OPh)3 > PPh3 ≈ PMe3 > IPr > PCy3 (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazol-2-ylidene). Depending on L these protolysis enthalpies with HI span a range of 50 kJ/mol. The Au–C

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

• distances range from 1.512 to 1.532 Å, which in most compounds except 4a is longer than the average sulfoxide bond length of 1.489–1.515 Å [45][46] and close to the bond length in DMSO [47]. The S–C(cat) bond distances range in the narrow range of values 1.782–1.789 Å. The S–C(R) distance varies in the

• range of 1.838–1.892 Å. If the C(R) atom is aromatic as in the case of 7a, the average S–C distance has a tendency to be slightly shorter (1.804 Å) due to a possibility of weak conjugation of the π-system in the aromatic ring with the S=O double bond, but nevertheless close to the corresponding value

• for 6a. The O–S–C(cat) and O–S–C(R) bond angles vary in the ranges of 104.2(2)–106.75(7)° and 103.6(3)–110.0(3)°, respectively. The torsion angle (C(R)–S–C(cat)–C(OH)) between the plane of the aromatic ring of the catechol fragment and the hydrocarbon group at the sulfur atom ranges from 66.7° to 84.3

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

• approaches [2][3][4][5]. In this context, comprehensive medicinal chemistry studies consistently highlight the prominence of isatin-derived frameworks among bioactive and anticancer agents [6]. The remarkable reactivity of the isatin scaffold arises from its dual functionality, combining an electrophilic C-3

• aromatic pattern of the isatin core. The IR spectrum showed a strong imine C=N band at 1610 cm−1, and the absence of the C-3 carbonyl stretching band confirmed complete condensation. The 13C NMR spectrum revealed multiple sets of closely related signals, consistent with the presence of three C=N

• retained the four-signal pattern of isatin (H4', H5', H6', H7'), slightly shifted by the new structural environment. In the 13C NMR spectrum, the amide carbonyl appeared at δ 176.5 ppm, while a key quaternary carbon at δ 61.0 ppm (C3‘) – formerly the C-3 isatin carbonyl carbon – confirmed the formation of

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

• products in acidic media subjecting the condensation products 3b and 4b to heating in glacial acetic acid at 50 °C for 6 hours revealing that compound 3b was stable whereas compound 4b decomposed into the starting reagents (see the TLC data in Supporting Information File 1, Figure S3). Apparently, after

• additionally due to C–H···π intramolecular interactions: φ1 = 106.8(2)° (N3–C13–C12–C5) and φ2 = 99.6(2)° (N4–C18–C12–C5) (Figure 2a). The molecules of 4,5-DPDAF are packed into stacks due to π-stacking interactions between diazafluorenes which are stabilized by C–H···N interactions between pyridine and

• 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

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

• isomers are formed together might be due to the equilibrium between A and C, although there are many unknown points. Conclusion In summary, we have developed a simple and selective procedure of the synthesis of (E)-1,2-dibromo-1,2-diphenylethylene from diphenylacetylene by using NBS and FeBr3 in CH2Cl2

• ; 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

• ., Ltd. for various supports in this work. Finally, we wish to express our acknowledgments for Kindai University Joint Research Center for use of facilities. Funding This work was financially supported in part by JSPS KAKENHI (JP24K08506) (Grant-in-Aid for Scientific Research [C]) and 2025 Kindai

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

• arrangement. Kinetics studies identified the most stable Z-isomer of the difluoro derivative (τ1/2 = 3.74/6.59 h at 60 °C in DCE/CDCl3). The monofluoro derivative embedded in a polystyrene film demonstrated photoresponsive behavior and remarkable stability by maintaining a macroscopically visible color change

• viscous liquids or slowly solidified powders, due to the long aliphatic polymerizable pendant, which significantly suppresses facile crystallization. Hence, the target molecules were obtained as semi-crystalline solids undergoing a melting process (1a–c) or as viscous liquids (1d–f) where only a glass

• normal conditions (20 °C, 101.325 kPa) with a Tg = −49 °C, monochloro analogue 1c is a crystalline solid with Tm = 33 °C. From this perspective, the chlorine atom is at the size boundary, thus the number of appended chlorine atoms most likely determines the degree of supramolecular organization, as

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

• afford triazoles IXa,c,d or, in case of product IXb with (R)-alanine methyl ester. The absolute stereochemistry of IXb is R. All compounds with defined absolute configuration described below were synthesized from IXb, thereby preserving the absolute stereochemistry and affording the corresponding R

• enantiomer. The synthetic routes of compounds Z1–15 are shown in Scheme 6. First, intermediates 2 and 3 were reacted under basic conditions in MeCN to obtain intermediate 4 which was subsequently reacted with bromides IXa–c to get compounds Z1–3 in 80–91% yield. Then, compounds Z1–3 were treated with with

• dioxaborolane 7 or boronic acid 9 and IXa–c. Next, Z16–18 and Z23–25 were obtained by Williamson ether synthesis from the intermediates 8, 10 and isoxazole intermediates 2. Finally, hydrolysis in the presence of LiOH and reduction in the presence of lithium aluminum hydride provided target compounds Z19–22 and

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

• oxidation conditions, reaction in the presence of DMSO and NaHCO3 under conventional or microwave heating to ≈100 °C, were applied to the bromides derived from these alcohols by treatment with PBr3, resulting in the desired aldehydes which successfully underwent reductive amination reactions with 2

• ester 13b into the corresponding amide using AlCl3 were not promising and therefore the hydrolysis of this ester to corresponding carboxylic acid 14 was tested. Using KOH in MeOH at 35–40 °C for the ester hydrolysis reaction resulted in decarboxylated compound 12b being isolated as the sole product in

• ester being recovered. Thus, for the preparation of the aldehydes we opted for reduction of the esters 13a–d and 13f to their corresponding alcohol derivatives (17) followed by oxidation to the aldehyde. Esters 13a–c were readily converted into the corresponding alcohols 17a–c in excellent yields of 92

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

• characterization of new brassinosteroid (BR) analogs, in which substituents with different electronegativities and molecular sizes have been attached to a C-22 benzoate function, are described. The biological activities of all new compounds were evaluated by using the rice lamina inclination test (RLIT) and

• inhibition of root growth of Arabidopsis thaliana. The RLIT data is compared with those previously reported for two series of compounds having the same substitution pattern at C-22 but different structure in ring A. This comparison revealed that a 2α,3α-dihydroxy configuration is more active than a 3

• matter of current interest. For example, derivatives of teasterone (3), compounds 4–11, and castasterone, compounds 12–14, with benzoyl function at C-22 (Figure 2) have been synthesized, and their bioactivities have been evaluated by BSIB, RLIT, and inhibition of root and hypocotyl elongation in A

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

• structure somewhat rotated out of planarity (dihedral angles between aromatic C–C and vinylic CH are 34°). This presumably still allows for some conjugative stabilization from the aromatic rings to the enone π-systems and reduces eclipsing interactions between the ortho-methyl groups and the vinylic H

• demonstrates the general viability of sulfinate addition to produce C-tertiary sulfones, but also implies steric limits to these processes in double intermolecular conjugate addition with Rongalite as the nucleophile. Our approach was to use competition experiments to indicate the relative reactivity of

• methanesulfinate or p-toluenesulfinate and 1 equivalent of Rongalite (50 °C, AcOH/H2O, o/n) led to a mixture of products. These results are tabulated in Table 1. Mixtures of cyclic and acyclic products were obtained in both cases. Our initial interpretation was that the ratios reflected the relative rates of

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

• heating were used. Notably, this process can proceed solvent-free at 140 °C, which is suitable for less reactive substrates. Various exo-cyclic alkenes obtained from cyclic (hetero)aliphatic ketones such as cyclobutanone, azetidinone, thienone, as well as endo-(hetero)cyclic alkenes containing oxygen

• due to the possibility of cycloaddition at the carbon–oxygen double bond (C=O) of the aldehyde, which acts as an alternative to the carbon–carbon double bond (C=C) [83]. In 2016, Sridharan reported a one-pot iridium-catalyzed three-component dehydrogenation/1,3-dipolar cycloaddition cascade reaction

• -nitro-1,2-diphenylcyclopropene 127 in primary, secondary, and tertiary alcohols, as well as using certain thiols. The authors suggest that the reactions proceed via a stage of heterolytic cleavage of the C–N bond of the starting 3-nitro-1,2-diphenylcyclopropene to form a cyclopropenyl cation, which then

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

• were recorded at 25 °C on a Bruker AVANCE III HD 500 or HDX 800 MHz NMR spectrometer equipped with a cryoprobe. The 1H and 13C chemical shifts were referenced to solvent peaks for CDCl3 at δH 7.26 and δC 77.2, respectively. UHPLC–LRESIMS analysis was performed using a previously reported method [32

• detailed below. The previously described plant compounds salicifoliol (1) [15][16] and (+)-pinoresinol (2) [17] were identified following 1D and 2D NMR (1H, 13C, COSY, HSQC, HMBC, and ROESY), [α]D, MS data analysis, and comparison with literature values. (+)-Salicifoliol (1): clear gum; [α]D25 +36.4 (c

• 0.09, MeOH); lit. [α]D25 +56.3 (c 0.06, MeOH) [33]; see Supporting Information File 1 for 1H and 13C NMR data in CDCl3; LRESIMS m/z: [M + H]+ 251, [M − H]− 249. (+)-Pinoresinol (2): brown gum; [α]D25 +55.5 (c 0.07, MeOH); lit. [α]D25 +20.0 (c 0.75, MeOH) [34]; UV–vis (MeOH) λmax (log ε) 230 (3.94), 279

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

• (TBHP, 0.6 equiv), which was added at 0 °C in three portions, affording 13-hydroxycasbene (8) as a single diastereomer in 48% isolated yield at milligram scale. The reaction could be performed on a gram scale albeit with a diminished isolated yield (39%, 79% brsm). We thought that with the most reactive

• -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

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

• -trimethoxybenzene (TMB) as the substrate and 3 equivalents of TFAA as the CF3 source, over 6 hours at room temperature (25 °C). Initially, white light irradiation was selected owing to its broad coverage of the visible spectrum (Supporting Information File 1, Figure S6). Screening of various organic photocatalysts

• afforded no more than 6% yield (Table 1, entry 6). Interestingly, MTBE, in contrast to the cyclic ether THF, gave a satisfactory yield of 27% (Table 1, entry 7). BuOAc provided a comparable yield of 28% (Table 1, entry 7), likely due to its higher viscosity (0.685 cP at 25 °C) compared with EtOAc (0.423 cP

• at 25 °C) [30]. These results established EtOAc as the most suitable solvent for the transformation. The effect of reaction time was also evaluated. Variation from 1 h to 12 h (Table 1, entry 8) demonstrated that 6 h (Table 1, entry 5) is optimal for achieving the highest yield. Optimization of the

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

• -ABL and c-ABL: Currently, the vast majority of chronic myeloid leukemia and about 20–30% of acute lymphoblastic leukemia are caused by chromosome translocation between chromosomes 9 and 22 [125]. The gene rearrangement leads to the expression of the oncogenic fusion protein, BCR-ABL and the loss of

• autoinhibition of the c-ABL kinase domain in BCR-ABL is the main cause of cancer [126]. Imatinib mesylate was the first tyrosine kinase inhibitor (TKI) targeting BCR-ABL [127][128]. It can competitively bind to the ATP binding site of c-ABL to inhibit the functions of c-ABL and BCR-ABL, thereby inhibiting cell

• degradation of BCR-ABL by PROTACS has been the focus of intensive pharmaceutical chemistry research. Interestingly, it was found that using different POI ligands and E3 ligands combinations can achieve efficient selectivity for BCR-ABL and c-ABL. This discovery is of great significance for the subsequent

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

• (Scheme 1). To support these working hypotheses, the reaction of 1 equiv [Cu(OH)(IPr)] with 2 equiv of formic acid in a sealed tube was followed by 1H NMR spectroscopy in deuterated toluene (C7D8). After 16 h at 110 °C, the formation of 1b was observed while no excess of formic acid was detected

• produced, the pressure change was measured as a function of time (see Supporting Information File 1, Table S1). By heating formic acid in toluene in the presence of 1 and 10 mol % of 1a, no evolution of gas was observed neither at 25 nor at 110 °C (see Supporting Information File 1, Table S1, entries 1–4

• ); conversely, by increasing the catalyst loading to 30 mol % (with respect to FA), an encouraging 26% conversion was observed at 110 °C (see Supporting Information File 1, Table S1, entry 5). However, to decrease the temperature and the catalyst loading, the generation of the Cu–H species by means of a silane

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

• Sophie Day-Riley Sona Krajcovicova Aryaman Raj Sokhal Jan L. Venne Paul Brear Marko Hyvonen Benjamin C. Whitehurst Jason S. Carroll David R. Spring Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, CB2 1EW, Cambridge, United Kingdom Department of Organic Chemistry

• 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

• 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

• Rasmus M. Borup Nicolai Ree Jan H. Jensen Department of Chemistry, University of Copenhagen, Copenhagen, DK-2100, Denmark 10.3762/bjoc.22.46 Abstract We present HAlator, a fully automated quantum chemistry (QM) workflow for computing C–H hydricities and explore its potential in predicting the

• regioselectivity of electron-rich C–H functionalisation reactions. The workflow was benchmarked against 35 experimentally determined C–H hydricities in DMSO, yielding a mean absolute error (MAE) of 4.43 kcal/mol and a root mean squared error (RMSE) of 5.45 kcal/mol. Leveraging this approach, we generated a dataset

• of 3278 C–H sites across 740 molecules to train a machine learning (ML) model based on CM5 atomic charge descriptors, achieving an MAE of 2.30 kcal/mol and an RMSE of 3.74 kcal/mol relative to QM-computed hydricities. The method was further applied to 250 hydride transfer-like reactions, including C

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

• 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

• 4 hours does the C(4)–H signal of compound 4a at δ 7.05 ppm in the 1H NMR spectra finally disappear. With optimized conditions in hand, we turned our attention to examine the substrate scope. As shown in Scheme 3, isoxazole derivatives bearing different electron-withdrawing groups in position 3 such

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

Continuous-flow carbonyl hydrogenation under subatmospheric to atmospheric hydrogen pressure enabled by robust heterogeneous Pt–Fe catalysts

• Hiroyuki Miyamura,
• Ryosuke Kajiyama,
• Shun-ya Onozawa,
• Yoshihiro Kon and
• Shū Kobayashi

Beilstein J. Org. Chem. 2026, 22, 575–582, doi:10.3762/bjoc.22.43

• 1.2 atm in this case (0.2 atm pressure loss). The yields of 1-phenetylalcohol (2a) and by-products 3a and 4a under these reaction conditions for each catalyst are summarized in Table 1. The commercially available catalysts (Pt/C, Pt/SiO2, Pt/Al2O3) and Pt/DMPSi‒Al2O3 showed poor to moderate reactivity

• ) was converted to the corresponding alcohol 2d in 89% yield under continuous-flow conditions at room temperature (Table 2, entry 3). The desired product 2d was obtained quantitatively at 50 °C (Table 2, entry 4). It is noteworthy that an analytically pure compound (confirmed by 1H and 13C NMR) was

• 80 °C under the continuous-flow conditions (Table 2, entry 11). The high catalytic performance of Pt‒Fe/DMPSi‒Al2O3 enabled the hydrogenation of substrate 1k even under almost atmospheric pressure hydrogen conditions. Stanolone (1l) is also a bulky ketone compound with a steroid skeleton, and its

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