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

• and peptide modifications introduce functionalities not achievable through recombinant methods alone, making them vital for fundamental research and biomedical applications [1][2][3][4]. Such chemistry underpins wide-ranging biological investigations including microscopy, proteomic analyses and tissue

• reagents, organic solvents or chaotropic agents must be avoided to preserve protein stability, preventing folding heterogeneity and supporting sustainability. Scalability. For therapeutic and industrial applications, modification methods should minimise waste and curtail costs, reflected in low process

• difference is often not sufficient for site-specific modifications. Consequently, recent effort has shifted towards targeting alternative less-frequent amino acid residues [82], as well as novel mechanisms such as linchpin-directed modifications summarized below. Various chemoselective methods for

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

• thiol [22][23][24][25], through nucleophilic aromatic substitution on the catechol ring [26][27], or under electrochemical conditions [28][29][30][31][32]. A number of methods exist for the conversion of sulfides into sulfoxides, proceeding via either oxidative or non-oxidative pathways. The controlled

• catechol moiety were detected. The yields of the target sulfoxides ranged from 42% to 89%. Compounds 3–6 were prepared and characterized as described previously (3, 4, and 6 [23], 5 [42]). The structures of new thioethers 1, 2, 7 and sulfoxides 1a–7a were confirmed by the spectral methods IR-, 1H NMR, 13C

• -R) were studied by cyclic voltammetry (CV) (Table 1). All experimental electrochemical methods and conditions are presented in Supporting Information File 1. In the anodic area, the electrochemical profile of thioethers 1, 2, and 7 exhibit two successive oxidative stages consistent with previous

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

• Olex2 [22]. The structure was solved by intrinsic phasing with SHELXT [23] and refined by full-matrix least-squares methods on F2 using SHELXL [24]. Commercially available chemicals were obtained from Scharlau, TCI and Acros and used as received. Synthesis of 25: Isatin (1, 2.98 g, 19.85 mmol, 1 equiv

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

• . However, there are currently only limited methods for their synthesis, which are complicated and typically based on modifications of 4,5-diazafluorenone. Herein, we systematically studied the Knoevenagel condensation of both 4,5- and 1,8-diazafluorenes with aromatic aldehydes and evaluated 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

• functionals (Table 3 and Supporting Information File 1, Figures S65–88). Both methods afforded the spectra that are similar in shape but either red or blue-shifted compared to the experimental data. The range-separated CAM-B3LYP functional was used to better describe the excited states and charge-transfer

• character of the investigated molecules. Anyway, both methods confirmed a minor effect of the halogen type, red-shifted λEmax values for monosubstituted E-isomers and the opposite trend for the Z-isomers. TD-DFT calculations revealed the most intense absorption bands of (E)- and (Z)-azobenzenes are

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

• derivatives have been found to be of interest in the development of organic materials with interesting properties [11][12]. The importance of imidazo[1,2-a]pyridines is evidenced by the plethora of recent review articles covering methods for their preparation [13][14][15][16] and functionalisation reactions

• atom, giving rise to benzamides, while Wu and co-workers [31] reported ring-opening to give either benzamides or α-ketoamides. This is in contrast to our own report, where only the oxalamide derivatives 18 were isolated. Two other oxidation methods, IBX and enzymatic oxidation using T. versicolor

• laccase in the presence of TEMPO and O2, were tested on compounds 17 in order to obtain the corresponding aldehydes, but both of these methods also gave rise to the ring-opened products 18. A detailed investigation into the mechanism of this ring-opening reaction was not conducted. However, this failure

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

• experimental and computational study of the diastereoselectivity of cyclic sulfone synthesis by reaction of Rongalite with doubly electrophilic dienones is presented. Computational methods, including density functional theory, conformational search methods, and internal reaction coordinate methods, have been

• the reactivity of other readily available sulfinate nucleophiles using competition and exchange experiments. Keywords: diastereoselectivity; Rongalite; sulfones; Introduction Sulfonyl groups are widespread in licensed drugs [1]. New methods for the incorporation of sulfonyl groups into organic

• product, we used density functional theory (DFT) and conformational search techniques based on tight-binding methods to find the energetically minimized structure of 7 (see Supporting Information File 1 for details on all computations). The lowest energy structure is depicted in Figure 3. It shows a

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

• the development of 1,3-dipolar cycloaddition over the past decade, examining the reactions of various dipoles, including azomethine ylides, with a wide range of dipolarophiles [22]. In reviews [23][24][25], various methods for the generation of azomethine ylides were discussed in detail, for example

• compounds were reviewed. Rare methods for preparing azomethine ylides using pyridylimines and α-silylimine were described. Electrophilic alkenes, styrene derivatives, and new, previously undescribed unsaturated substrates were frequently used as dipolarophiles. The contribution of our research group to the

• -quinolyl, 2-pyridyl, and 4-pyridyl fragments. It is worth noting that 1-(4-nitrophenyl)-1,3-butadiene (40) and 1,1-bis(2-pyridyl)ethylene (41) also proved to be suitable substrates in this reaction (Scheme 20). It was demonstrated by computational methods (DFT) that electronic effects within the

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

• collected on a Rigaku XtaLAB synergy diffractometer using Cu Kα radiation at 100.0(1) K using an Oxford Cryostream cooling device. The structure was solved by direct methods and difference Fourier synthesis [36]. Hydrogen atoms bound to the carbon atom were placed at their idealized positions and included

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

• efficient macrocyclization methods, including tetracarbonylnickel-promoted cyclization of allylic dibromide [17][18], copper-mediated intramolecular carbene–olefin cyclization [19], titanium-induced intramolecular carbonyl coupling [20], and organozinc carbenoid-mediated intramolecular cyclopropanation [21

• . With the ability to facilely obtain the terpene skeletons such as casbene and germacrene A by this heterologous terpene-producing platform, accessing other casbane- and germacrene-type of natural products and their analogues becomes possible if suitable chemical and enzymatic methods are available for

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

Harnessing light energy with molecules

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

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

• a key property for characterizing the light harnessing efficiency of a photoswitch. In the article by Volker, Steen, and Crespi [18], a convenient and reliable fiber optic spectroscopic setup for determining this quantum yield is reported and was benchmarked for azobenzene against other methods

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

• experimental co-crystal structure of the bound complex, standard medicinal chemistry principles are used to probe structure–activity relationships (SAR) and determine the key interactions that form a minimal pharmacophore, supported by classical physics-based molecular modelling methods such as molecular

• candidate small molecules for experimental validation in functional assays. Nascent examples of ML approaches In contrast to physics-based models for extracting pharmacophores and predicting small molecule binders, ML methods are now emerging as alternatives for accomplishing these tasks. An early

• tractable, although synthetic accessibility was noted to be somewhat restricted by the highly sp3-rich nature of the generated molecules. New iterations of these methods have since been reported by the authors [23], though experimental validation of predictions remains to be reported at the time of writing

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

• approaches can be regarded as among the most environmentally sustainable methods for trifluoromethylation. MacMillan and co-workers reported the photochemical trifluoromethylation of arenes and heteroarenes using Ru- and Ir-based photocatalysts together with trifluoromethanesulfonyl chloride (TfCl) in the

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

• electron-rich C–H functionalisation reactions. Methods Datasets To validate our QM workflow, we use a dataset of 35 experimental C–H hydricities in dimethyl sulfoxide (DMSO, 26 compounds) and acetonitrile (MeCN, 9 compounds) from Parker and co-workers [7]. As 35 C–H hydricities are insufficient to train an

• that evaluates the accuracy of different levels of theory, ranging from semiempirical methods (xTB [16]), composite electronic structure methods (r2SCAN-3c [19]) to DFT methods (M06-2X[21], CAM-B3LYP [22][23]). All methods are evaluated either as single-point calculations or optimization and frequency

• predictive accuracy for sterically demanding carbene insertion reactions, where all current methods underperform. While the ten literature examples discussed here provide promising proof-of-concept evidence, establishing the general utility of hydricity for regioselectivity prediction will require validation

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

• strategies to combat the antibiotic resistance include, in particular, the synthesis of novel antibacterial agents based on isoxazole derivatives [17]. In this regards, the development of efficient and convenient methods for the sulfonyl-containing isoxazoles synthesis has received great attention. The most

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

• , including ketones and aldehydes, to alcohols is a fundamental and important reaction in organic synthesis. One of the most ideal methods is catalytic hydrogenation, however, the hydrogenation of ketones generally requires harsh reaction conditions, such as high temperature and high pressure. We developed a

• as functional materials and pharmaceuticals [1][2][3][4]. While stoichiometric reagents and catalytic methods are widely developed for this transformation, one of the most ideal methods is heterogeneous catalysis using molecular hydrogen as a reductant, which realizes 100% atom economy [5][6][7][8][9

• ][10][11][12]. In this context, advanced technologies represented by the precise control of the bimetallic structure of a heterogeneous catalyst, mechanochemical hydrogenation, and continuous-flow methods using packed-bed reactors greatly contributed to advancing this transformation [9][11][12][13

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

• . Supporting Information Supporting Information File 16: Experimental part. Acknowledgements We acknowledge important conceptual help and generous support with methods and instruments from the group of Andrea Musacchio at the Max-Planck-Institute of Molecular Physiology, Dortmund. Funding CG, PR, CB, PB, DB

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

• in the mixture of melifoliones was increased to a maximum of about 10–15%. Since it was not possible to distinguish or even to separate the isomeric melifoliones using chromatographic methods, their quantitative ratio after cyclization of 5 could only be determined using the 1H NMR spectra. After

• and data acquisition. Data collection was therefore applied with seriously elongated exposure time. The crystal structure was successfully solved using methods as implemented in the SHELXT program [16], followed by refinement with SHELXL [17]. The refined asymmetric unit was found to contain about

• from mixtures of melifoliones 1 and 2 using the applied chemical methods. Thus, it is clearly proven, that 4 cannot be built as an artifact during the isolation. Therefore, it is likely that the biosynthesis of the quinol 4 occurs via enzymatically catalysed oxidation in the leaves of Melicope

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

• are not necessarily consecutive and may not be readily dissected. Furthermore, as the reaction intermediates are isomers with mainly similar structural fragments, it is difficult to distinguish them by the usually employed spectroscopic methods because of overlapping signals [22][30][33]. Along these

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

• using CrCl3 and NbCpCl4. The last steps towards 1 are known procedures [68]. By comparison to former methods, this technique does not require further desulfonylation after the macrocyclization [19][68]. Choi and co-workers used a previously reported protocol on stereo- and regioselective allene-Prins

• the targeted derivatization of 1 for future works [110]. An overview of methods, including the respective fragments, steps and scales, is shown in Table 1. Given the importance of 1 for medicine and the reasearch interest in 1`s derivatives to potentially enhance its potency, this research field will

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

• carboxylic acid derivatives such as esters, acyl chlorides and anhydrides with hydroxylamine salts [41]. A variety of coupling or activating agents were also employed in case of simple addition of hydroxylamine to carboxylic acid compounds [42][43][44]. In addition, alternative methods starting from

• , following the method reported by Camiolo and Gale [21], affording a yield of 85%. Among several procedures used for the direct hydroxyaminolysis of carboxylic ester substrates, Beillard et al. highlighted the superiority of a DBU (1,8-diazabicyclo[5.4.0]undec-7-ene)-mediated route over the classical methods

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

• has been partially summarized in existing reviews [38][39]. This article aims to provide a comprehensive overview of reported methods for the synthesis of remote biaxial chiral molecules, focusing on three main synthetic strategies: direct one-step synthesis of biaxial systems, sequential formation of

• in catalysis, drug discovery, and functional materials. Review One-step construction of remote biaxial chiral molecules In recent years, the development of asymmetric catalytic methods, including both transition-metal catalysis and organocatalysis, has provided powerful tools for the one-step

• exceeding 60%. Sequential construction of distal biaxial chirality via stepwise axis formation Although one-step catalytic methods enable the efficient and direct construction of remote biaxially chiral molecules, the spatial interactions between multiple chiral axes can make it challenging to fully control

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

• yields (20–41%) and proceeds without the use of explosive peroxides (such as H2O2), which are commonly employed in methods reported earlier. The avoidance of explosive peroxides in the present method enables safe operation, easy scale-up, and also the synthesis of taxifolin derivatives with oxidant

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

• carried out under a nitrogen atmosphere using standard Schlenk line methods. Reagents and solvents were obtained from GK Life Sciences Pvt. Ltd. and used without further purification unless otherwise stated. Thin-layer chromatography (TLC) was performed on silica-gel-coated aluminium sheets (silica gel 60

• docking with selenium-containing ligands, the parameter file (AD4.1_bound.dat) was included. The resulting protein–ligand interactions were analysed using Discovery Studio Visualizer. Biological methods Cell culture The National Centre for Cell Science (NCCS), located in Pune, India, provided the MDA-MB

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

• described methods [14][15][16] as depicted in Scheme 2. The 7-Amino-substituted 1,3-oxazolo[4,5-d]pyrimidines 1–9 were obtained with high yields (65–80%) by the reaction of 2,5-diaryl-7-chloro-1,3-oxazolo[4,5-d]pyrimidines II with the corresponding amine (aminoethylamines [17], cytisine and N-methyl-ᴅ