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

• has led to the development of labelling techniques, wherein the C-terminal carboxylate can be functionalized via visible-light photoredox decarboxylative catalysis (Scheme 2d) [23]. Similarly, decarboxylative alkylation has been applied to complex proteomes to enable proteome-wide C-terminal profiling

• substitution → hydrolysis; Scheme 8) [79], laying the groundwork for ligase development [80][81]. Lysine residues are abundant and typically solvent-exposed [82], hyper-reactive variants have been reported, and have led to the development of tools such as “K-lock” [83][84][85]. Unfortunately, the reactivity

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

• ]. The same principles apply to other alkenes and nucleophiles (alcohols, water) [85]. Using acetylene instead of ethylene gives first the analogous mono-insertion product, with the vinyl ligand trans to N. The mono-vinyl complex (C trans to N) could be isolated. Adding excess acetylene led to the

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

• observed relative stereochemistry in 25. However, alternative pathways, cannot be excluded. To address the generality of this transformation, a small set of substituted isatins was examined under the conditions used for the formation of 25. Reactions with 5-bromoisatin and 5-nitroisatin led to complex

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

• efficient photoswitches. In general, all monohalogenated switches reached higher photoconversion by ≈20% as compared to dihalogen-substituted ones. However, it should be noted that the absorption maxima of dihalogenated switches are blue-shifted and, provided a short-wavelength LED will be used, the

• yellow upon irradiation with 355 nm LED (Figure 10A) reflecting the E → Z switch. The irradiated sample was kept in the dark at 22 °C and the magnitude of color change was visually verified after 20, 40, and 90 days as shown in Figure 10B–D. Even after 90 days in the dark, high color saturation was still

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

• previous study demonstrated that in a liver fibrosis model and a chronic fast food diet (FFD)-induced MASH mouse mode [26][27], the combination of an ASK1 inhibitor and an FXR agonist led to a more pronounced reduction in hepatic fibrosis than either monotherapy [28]. Recently, several publications

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

• -chloroaniline. Alternative oxidation conditions such as PCC, IBX or T. versicolor laccase applied to the alcohols led only to oxidative ring-opening to give oxalamide derivatives, with no aldehyde being isolated. Keywords: 3-aminoimidazo[1,2-a]pyridine-2-carbaldehydes; Groebke–Blackburn–Bienaymé reaction

• –99% using LiAlH4 reduction (Scheme 3). Unexpectedly, reduction of 13d and 13f led to the same compound, the dehalogenated derivative 17d in 96% and 51% yield, respectively, presumably through nucleophilic aromatic substitution [29]. Oxidation of alcohols 17a–d using pyridinium chlorochromate (PCC

• similar reactions on alcohols 17b–d led to the corresponding ring-opened products 18b–d (Scheme 4). The ring-opened products were isolated in yields of 26–36%, with loss of one carbon atom occurring (-CH2OH). To test whether C-2 decarboxylation could have immediately preceded ring-opening, decarboxylated

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

• 1b was provided by derivatization of both molecules in ways that confirmed their relative stereochemistry by taking advantage of the different symmetry elements present in each case. Thus, both reductive amination and hydride reduction of C2-symmetric 1a led to the isolation of the only possible

• 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

• various aromatic and aliphatic substituents; vinylaryl carbinols with electron-withdrawing and electron-donating substituents in the phenyl ring have successfully proven themselves as dipolarophiles; replacement of the aryl substituent with heteroaromatic or aliphatic ones also led to acceptable results

• -alkylmaleimides 63, with the formation of cycloadducts 68. Next, without isolating the intermediate product 68, the resulting reaction mixture was used for the intramolecular (3 + 2) cycloaddition step with alkynes 69 and alkenes 70, which led to the formation of cycloadducts 71 and 72 with high

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

• reported. In this study, we chemically investigated the seeds of Eremophila maculata for the first time, which led to the isolation and characterization of two known plant metabolites, (+)-salicifoliol and (+)-pinoresinol. Due to the reported biological properties of the lignan natural product

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

• , entries 4 and 5). The influence of catalyst loading was then examined. Raising the photocatalyst concentration to 2 mol % led to yields of 64%, 64%, and 78% under white, violet, and blue light, respectively (Table 1, entries 3–5). A further increase to 5 mol % (Table 1, entry 5) afforded 87% yield

• TMB (Table 3, entry 2), which led to an even lower yield of 51% (isolated yield was 39% for entry 2). Further scale-up to a 1 g level, carried out in a Schlenk flask with a 38 mm inner diameter, afforded a comparable yield. In contrast, implementation of a continuous-flow setup provided a higher yield

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

• steric reasons rather than electronics. In fact, the reaction of trifluoroacetic acid led to the same outcome as acetic acid (Scheme 4, see Supporting Information File 1, section 8). Theoretical as well as experimental investigations to assess the mechanism of this transformation are still ongoing. The

• intensively investigated [44][61]. Thus, the decomposition of a 1:1 HCO2H/NEt3 mixture in the presence of different NHC–Cu complexes was explored (Table 1). No conversion was achieved with [Cu(OH)(IPr)] (1a). To our delight, the reaction in the presence of its chloride analogue 1d led to 24% conversion after

• generating an inactive species [44]. Electronic effects were next investigated. Electron-rich anilines like p-toluidine or p-anisidine led to lower conversions than p-chloroaniline (Table 2, entries 5, 8, and 10). As highlighted in Table 2, no correlation between the basicity of the amines and the

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

• construction. The synthesis of the ATP-site binder began with the alkylation of commercially available methyl 3-aminobenzoate (3) using bromoacetyl bromide. Although initial purification via silica gel chromatography led to substantial product loss, isolation by simple aqueous workup afforded the intermediate

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

• ]. Briefly, these reporter strains express different fluorescent proteins depending on the mechanism of action of the antibiotic. In case of activation of the antibiotic-induced SOS-response, the rfp gene was expressed in the cell of the reporter strains, and disruption of the translation mechanism led to

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

• -JD-6 could directly degrade FGFR2 from the plasma membrane. KATO III gastric cancer cells were incubated with 500 nM LC-JD-6 for 12 hours, followed by flow cytometric quantification of cell surface FGFR2 expression. As shown in Figure 4b and Figure 4c, LC-JD-6 treatment led to a marked decrease in

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

• . Finally, the catalytic activity was revived again, and quantitative conversion was observed over 90 h of total running. Water as contaminant in EtOAc or organic compounds strongly adsorbed on the catalyst’s surface may have led to its deactivation; however, they could be removed by simple heating. We

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

• of rac-1a giving (R,R)-2a of 99% ee and (S)-1a of 45% ee with 37% conversion (krel = 754; Table 1, entry 4). The lower catalyst loading (5 mol %) led to an unsatisfactory conversion (18%) probably due to the decomposition of the molybdenum catalyst prior to the completion of the reaction (Table 1

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

• (vide infra). Again, molecular docking of peptide and tweezer moiety 2a on survivin led to stable arrangements on survivin, suggesting simultaneous occupation of the H3 binding site and potential complexation at Lys-121 (Figures S10 and S11 in Supporting Information File 1). The triazole linker may act

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

• -position in regard to the OH-group at C-10b (Table 2). Synthesis of melifoliones Melifolione A (1) was prepared according to the method of Wang and Lee [5] by heating phloroacetophenone and citral with ethylene-diammonium diacetate (EDDA) in DMF. However, reaction of the educts in pyridine at 60 °C led to

• dichromate in acidic solution or with potassium permanganate in acidic or alkaline solution led to complete decomposition of the melifoliones. A solution of the melifoliones in methanol with addition of methylene blue decomposed completely into undefined products within 24 hours when exposed to sunlight and

• atmospheric oxygen. Oxidation with potassium peroxodisulfate (Oxone®) according to a method by Carreño et al. [7] led to a complex mixture of compounds in which the quinols 3 and 4 could be excluded. While oxidation with alkaline hypochlorite solution gave a mixture of not identified chlorinated products

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

• (see Supporting Information File 1, Figure S10). The photosensitized reaction in the presence of Ir(ppy)3 or 1-butyl-7,8-dimethoxy-3-methylalloxazin (4) as an alternative catalyst [44][45] with λex = 405 nm (LED) was investigated by in situ 1H NMR spectroscopy. In both cases, the photoreaction was

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

• within their isolation study on halichondrin B, in 1986, Hirata and Uemura showed its promising activity against murine cancer cells [6], which led to a great interest in the pharmaceutical society [7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Only 6 years later, Kishi and co-workers first

• the secondary alcohol unit of 71 was changed via oxidation and stereospecific reduction, then 1,4-reduction of the enone and treatment with camphorsulfonic acid led to fully cyclized intermediate 72 as a single isomer. During this process the acetate groups were cleaved off and had to be reinstalled

• 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 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

• ]. Based on the Beer–Lambert law, the concentration was calculated to be 2.69 μM. Attempts at further concentration led to precipitation, indicating limited solubility at higher concentrations. The HDAC inhibitor–nanogold probe inhibits HDAC enzymatic activity in the CoREST complex We first wanted to

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

• macrocyclic core through simple acylation of p-aminocalix[4]arenes with the respective phosphorous-containing activated esters. Such grafting of well-known receptor units onto a common platform has led to substantial amplification of the efficiency of lanthanide and actinide extraction from acidic media by

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

• 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

• excess of azomethine ylide precursors (2.5:2.5 equiv sarcosine/CH2O) led to 87% yield. The obtained pyrrolidines represent a class of labile compounds with a strained C2–C3 bond. The presence of the benzoyl and sulfonyl groups able to eliminate [5][42] and generate an anion at the 3rd position should

• -1-amines 4c–e,h were isolated in 40–69% yields (Scheme 2). Introduction of the m-nitro substituent led to partial resinification during the ring-cleavage step and significant decrease in the reaction outcome (products 4f,g). We have demonstrated that ethyl bromide, benzyl chloride, allyl bromide

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

• transformation of the target amide in the presence of more reactive functional groups (Scheme 24b). Using 9-mesityl-3,6-di-tert-butyl-10-phenylacridinium tetrafluoroborate (Mes-Acr-Ph+BF4−) as the photoredox catalyst under 450 nm LED irradiation, the PMB anilide unit was chemoselectively activated and cleaved in

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

• -proline), tetracyanoethylene, chalcone, and dimethyl acetylenedicarboxylate all failed to produce the target spiro adducts – chalcone and dimethyl acetylenedicarboxylate showed no reactivity, while tetracyanoethylene led to complete resinification. The structure of the products, including the

• -fused adducts 4f, 4g, 4i, 4k, and 4l. Confocal microscopy showed that co-incubation of Sk-mel-2 cells with adducts 4f, 4g, 4i, 4k, and 4l led to significant changes in the structure of their actin cytoskeleton resulting in stress fibers disappearance (granular actin was found in the cytoplasm of up to

• , 4k and 4l was equal to 25, 19, 31, 21, 23, and 19% for the tested compounds and control sample, respectively. As can be seen from the obtained data the wound healing ability are consistent with the cytoskeleton data. Compounds 4g and 4l, which led to less stress fibers (87 ± 22%, 71 ± 16% vs 46 ± 7