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

• chromatography, while also offering well-defined pharmacokinetic and pharmacodynamic profiles. Homogeneous batches of labelled proteins thus improve therapeutic indices and reproducibility, key determinants of clinical trial outcomes. Usability. Effective strategies act directly on native proteins, avoiding

• sites (to improve stability and solvent tolerance). The engineered enzyme PGAA1-AcRd3 selectively introduced a benzoyl group at the N-terminus of chain A, whereas PGAdimer-HRd3 catalysed deprotection enabling formation of dimerised insulin candidates under mild chemoenzymatic conditions. Chromatography

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

• reduced pressure and the mixture was purified by column chromatography (DCM/Me2CO gradient from 8:2 to 6:4) to give 30 as yellow oil (1.04 g, 2.99 mmol, 61%). HRMS m/z: [M + H]+ calcd. for [C20H21N4O2 + H]+, 349.1665; found, 349.1674; 1H NMR (300 MHz, MeOD) δ 7.19–7.17 (m, 2H, H4’, H4’’), 6.92 (ddd, J

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

• condensation using TiCl4 and pyridine, is cheaper, easier to apply, and the pure target product simply precipitated from the reaction mixture instead of extraction and purification by column chromatography. Di(pyridin-2-yl)methylene)-9H-diazafluorenes Furthermore, since ketones are generally considered to be

• additional purification. Reaction mixtures were monitored by TLC using Macherey-Nagel pre-coated TLC-sheets Alugram Xtra SIL G/UV254. For column chromatography Macherey-Nagel Kieselgel 60 was used. NMR spectra of products were recorded with Bruker AV 300, Bruker AV 400, and Bruker DRX 500 spectrometers in

• , methanol, hexane, and dried in air. In the case of absence of any precipitate, the solutions were extracted with chloroform, dried over anhydrous MgSO4 and concentrated under reduced pressure. The products were purified either by column chromatography on silica gel (eluent ethyl acetate) or by addition 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

• racemic 2-hexalicene iminoester 49 to C60 fullerene 50 (Scheme 23). During the reaction, two diastereomeric helicenepyrrolidino[3.4:1.2][60]fullerenes 51a and 51b are formed with a good enantiomeric excess. Further separation of the two diastereomers using column chromatography allows one to obtain

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

• -Aldrich. All solvents used for chromatography, UV–vis, ECD, [α]D, and MS were Honeywell Burdick & Jackson brand or Lab-Scan HPLC grade. H2O was filtered using a Sartorius Stedium Arium Pro VF ultrapure H2O system. Plant material E. maculata seeds used in these studies were obtained from the NatureBank

• -dried and ground seeds of E. maculata (10 g) were extracted with CH2Cl2 (250 mL, 2 h; 250 mL, 16 h) to afford 120.5 mg of crude CH2Cl2 extract. Subsequent extraction with MeOH (250 mL, 2 h; 250 mL, 16 h) afforded 1.43 g of crude MeOH extract. The CH2Cl2 extract (120.5 mg) was subjected to chromatography

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

• diastereomers (dr = 5:3) under Luche reduction conditions. These two diastereomers were difficult to be separated from each other using normal column chromatography and therefore were used in the next deoxygenation steps as a mixture. Attempts to form the xanthate for Barton–McCombie deoxygenation [61][62], or

• could be easily separated by column chromatography, and their physicochemical data were in consistent with those reported [35]. Conclusion The use of the chiral pool substrates containing complex chiral skeletons and suitable positioned functional groups would change the starting point of natural

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

• decomposition in the presence of PhSiH3 was investigated. Surprisingly, gas-chromatography analyses showed that only H2 was released. Remarkably, neither CO nor CO2 were detected (see Supporting Information File 1, section 5). To obtain more information on the mechanism of this reaction, isotopic labeling

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

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

• and 9b, respectively, but all attempts to separate the isomeric epoxides 9a and 9b by column chromatography or crystallization failed. Eight-membered rings are known to preferentially adopt boat-chair conformations, which minimize torsional and transannular strain [24]. To further rationalize the

• ) MHz Bruker spectrometers and are reported in δ units with SiMe4 as internal standard. HRMS spectra were obtained on a Bruker microTOF-Q or Agilent 6530 Accurate Mass Q-TOF instrument. Melting points were determined on a GallenKamp MPD 350. Column chromatography was performed on silica gel (60 mesh

• under reduced pressure. The crude product was purified by silica gel column chromatography eluting with pure hexane to give as the first fraction monoepoxide 6 (1.09 g, 8.78 mmol, 95%, a colourless oil) and as the second bisepoxide (0.07 g, 0.5 mmol, 5%, a white solid). The spectroscopic data are in

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

• , Germany). High resolution mass spectra were recorded on a FTHRMS-Orbitrap mass spectrometer (Thermo-Finnigan, Waltham, MA, USA). Merck MN silica gel 60 M (0.04–0.063 mm) was used as stationary phase for column chromatography. TLC was performed on silica gel 60 F254 plates with UV-detection. Solvents and

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

• layer was separated and dried with Na2SO4. The drying agent was filtered off, the solvent was removed under reduced pressure, and the crude product was purified by column chromatography (SiO2, n-hexane, Rf = 0.44) and recrystallization from n-pentane. The product was obtained as colorless cubes (84.0 mg

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

• subsequent oxy-Michael reaction. The mixture (137 + 138) was treated with p-TsOH leading to alcohols 139 and 140, which were separated via chromatography. From 140, Bn-deprotection of the primary, followed by Bn-protection of the secondary alcohol unit afforded 141 in 52% yield. Eventually, the ester motif

• allylated with crotyl bromide according to a procedure from Loh and co-workers [92]. The diastereomeric mixture thus obtained was separated via chromatography and (R)-151 was protected using BnBr. After hydroboration–oxidation and DMP-oxidation to the respective aldehyde, Ohira–Bestman reaction was applied

• esterification with EtI were conducted to form 318. TBDPS-protection and reduction yielded alcohol 319 in 58%, which was further oxidized to the respective aldehyde and olefinated leading to a 4:1 (Z/E) mixture of 320. The isomers were separated via chromatography, then, (Z)-320 was deprotected under acidic

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

• using thin-layer chromatography, with the appearance of the characteristic red spot upon treatment with FeCl3 confirming the presence of the hydroxamic acid functionality. Moreover, the formation of the tetra-hydroxamic acid product was confirmed by 1H NMR spectroscopy in deuterated DMSO, as evidenced

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

• to its corresponding NHS ester 8 and residual starting material was removed by column chromatography. The Boc-protecting group was removed under anhydrous conditions in good yield and the structure of 9 was confirmed by NMR spectroscopy. Compound 9 was maintained as the TFA salt for the final step

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

• (1.2 equiv) was performed in CH3CN, using t-BuOLi (1.2 equiv) as base in the presence of a catalytic amount of ZnCl2. Due to the high efficiency of the reaction, no purification of product (±)-4a by column chromatography was necessary after post-treatment and the product could be directly used in the

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

• 1.5 h. Thin-layer chromatography (TLC) was used to track the reaction progress. Upon completion of the reaction, ice-cold water was used to quench the reaction mixture, and the mixture was extracted with ethyl acetate. After two water and brine washes, the organic layer was dried over anhydrous

• magnesium sulfate (MgSO₄) and concentrated under low pressure. Column chromatography was performed to purify the crude product using a solvent ratio of petroleum ether to ethyl acetate (85:15), which yielded a yellow solid. Yield: (295 mg, 54%). mp: 156–157 °C; 1H NMR (400 MHz, CDCl3) δ 8.62 (d, J = 7.3 Hz

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

• copper complex (although an extraction procedure for complex destruction using Na2S2O3 was applied), which was difficult to separate from the relatively polar free calixarene 37 using column chromatography. In line with this, when toluene-soluble CuI·P(OEt)3 was used as a catalyst (in this case heating

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

• liquid chromatography–mass spectrometry. Their anticancer activity was assessed against human cancer cell as well as non-cancer cell lines. Three compounds, 1, 3, and 9, were the most cytotoxic to HeLa cells (IC50 = 6.13 ± 1.95, 13.99 ± 1.80 and 49.92 ± 3.98 μM, respectively). However, only compounds 1

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

• extraction or column chromatography. On the other hand, upon performing the reaction with amines in acetonitrile we did not observe the formation of benzamides. Presumably, debenzoylation occurred in basic media with water traces and cesium benzoate was discarded upon work-up. The presumable mechanism of the

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

• mixture by preparative TLC or column chromatography. Notably, compounds 4a, 4e, and 4k were purified by crystallization. Detailed synthetic and isolation procedures for all compounds are provided in Supporting Information File 1. We regret to state that when forming a mixture of diastereomers, we were

• unable to isolate individual products either by chromatography or by recrystallization. The proposed reaction mechanism is shown in Scheme 5, where it can be seen that the intermediate azomethine ylide, acting as a 1,3-dipole, undergoes a [3 + 2] cycloaddition with N-substituted maleimides 3a–p. The

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

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

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

• chromatography on silica gel with a methanol-containing eluent, isolated pyranoquinoline 14 underwent alcoholysis, converting it into the corresponding methyl ester 10 at the column outlet. These observations further support the mechanistic considerations of the four-component reaction discussed earlier

• products were also obtained via the four-component reaction using non-nucleophilic acetonitrile as solvent. However, this method requires subsequent purification by preparative chromatography, and, as noted, pyranoquinolines 14a–c readily undergo alcoholysis on silica columns with methanol-containing

Configuration–packing synergy enabling integrated crystalline-state RTP and amorphous-state TADF

• Ruiyan Wang and
• Yunan Wu

Beilstein J. Org. Chem. 2026, 22, 224–236, doi:10.3762/bjoc.22.16

• dried crude product was purified by column chromatography using a solvent mixture of dichloromethane and n-hexane in a 1:2 volume ratio. The purified product 4 was obtained as a white solid in a yield of 2.53 g (91%). Synthesis of 5-(3-(9H-carbazol-9-yl)phenyl)-2-(p-tolyl)isoindoline-1,3-dione (1) For

• sulfate (Na2SO4) to remove any traces of water. The dried solution was then filtered to remove the drying agent and concentrated under reduced pressure to remove the solvent. The resulting crude product was purified by column chromatography using a 1:2 volume ratio of dichloromethane and n-hexane. The

Synthesis of diaryl phosphates using phytic acid as a phosphorus source

• Kazuya Asao,
• Seika Matsumoto,
• Haruka Mori,
• Riku Yoshimura,
• Takeshi Sasaki,
• Naoya Hirata,
• Yasuyuki Hayakawa and
• Shin-ichi Kawaguchi

Beilstein J. Org. Chem. 2026, 22, 213–223, doi:10.3762/bjoc.22.15

• its light-brown appearance was identical to that of the product synthesized from commercial phytic acid. High-performance liquid chromatography (HPLC) analysis results indicated that the purity of 2a derived from the extracted phytic acid was greater than 95% (Supporting Information File 1, Figure S4

Base-promoted deacylation of 2-acetyl-2,5-dihydrothiophenes and their oxygen-mediated hydroxylation

• Vladimir G. Ilkin,
• Margarita Likhacheva,
• Igor V. Trushkov,
• Tetyana V. Beryozkina,
• Vera S. Berseneva,
• Vladimir T. Abaev,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2026, 22, 192–204, doi:10.3762/bjoc.22.13

• ethanol (Scheme 5, VII). However, under these conditions only decomposition of 4g was observed, and neither deacetylated nor hydroxylated products were isolated. Interestingly, chromatography of 4g on neutral alumina resulted in elimination of the sulfonylimine group to give compounds 5g. Therefore, the

Streptoquinolines A and B, new antibacterial meroterpenoids produced by Streptomyces sp. TMPU-A0679

• Akiho Yagi,
• Hitomi Tomura,
• Ami Konno and
• Ryuji Uchida

Beilstein J. Org. Chem. 2026, 22, 185–191, doi:10.3762/bjoc.22.12

• shaker (180 rpm) at 27 °C for 7 days using a malt extract-based production medium. Harvested mycelia (1.0 L) were extracted with acetone and ethyl acetate, and purification was guided by antibacterial activity against VRE. The crude extract (922 mg) was subjected to ODS column chromatography followed by