The surprising reaction of (chloro- and methanesulfonyloxy)(phenyl)methylphosphonates and –(phenyl)methylphosphine oxides with potassium diphenylphosphide followed by oxidation

• Zsuzsanna Szalai,
• Janka Bednárik,
• András Miskó,
• Angéla Takács,
• László Kőhidai,
• László Drahos and
• György Keglevich

Beilstein J. Org. Chem. 2026, 22, 1160–1167, doi:10.3762/bjoc.22.93

• afford a single isomer. However, in the instance, when Ar = 4-MePh, the selectivity may be explained by electronic reasons, as the P atom of the P(O)Ph2-function is more electrophilic than that of the P(O)(4-MePh)2 moiety. Purification by column chromatography afforded products 8a–e in 37–56% yields

A cascade synthesis of 2-aminothiochromones from 2-fluorophenyl ketone and thiocarbonyldiimidazole

• Kai Zhang,
• Haofan Shao,
• Kangjun Liao,
• Ying Xu,
• Shimei Du,
• Yanfang Zhao,
• Gang Li,
• Wenzhen Xu,
• Haihong Huang and
• Peng Li

Beilstein J. Org. Chem. 2026, 22, 1151–1159, doi:10.3762/bjoc.22.92

• thiocarbonyl group of TCDI (1a’’) with displacing one molecule of imidazole forms intermediate A, which was detected by mass spectrometry. However, intermediate A is unstable and rapidly cyclizes during work-up or purification. This process proceeds via a second deprotonation to generate a thiolate anion (A

Construction of CF₂ moieties in FDA-approved drugs (2016–2025): industrial routes, mechanisms, and scale-up considerations

• Wenyan Yao,
• Huanhuan Zhang,
• Xiaolong Yang and
• Feng Liu

Beilstein J. Org. Chem. 2026, 22, 1122–1150, doi:10.3762/bjoc.22.91

• NaIO4 and RuCl3. This process required no chromatographic purification, and after crystallization, the two-step yield was 73% on a 1.4 g scale. Although the differential scanning calorimetry (DSC) onset and energy places 2-PySO2CF2H above the Pfizer modified Yoshida thresholds, the compound structure

Discovery of sugarnitriles A and B, and structural reassignment of SF-2140, from a sugarcane endophytic actinomycete Amycolatopsis sp. JS-O27

• Qiuyun Li,
• Ying Liu,
• Baoyue Wei,
• Yu Sun,
• Di Mao,
• Yanmin Zou and
• Shan Lu

Beilstein J. Org. Chem. 2026, 22, 1114–1121, doi:10.3762/bjoc.22.90

• are currently underway. Experimental General experimental procedures All reagents and solvents were purchased from commercial suppliers, including Adamas, Adamas life, and Greagent, and used as received without further drying or purification. 1D and 2D NMR spectra were recorded at 25 °C on a Bruker

Synthesis and acaricidal activity against Varroa destructor of α- and γ-costic acid dimers

• Alessandro Santarsiere,
• Ernesto Santoro,
• Maria Letizia Ciavatta,
• Marianna Carbone,
• Sonia Ganassi,
• Cosimo Tedino,
• Antonio De Cristofaro,
• Antonio Evidente and
• Stefano Superchi

Beilstein J. Org. Chem. 2026, 22, 1088–1096, doi:10.3762/bjoc.22.87

• important crops such as legumes and cereals [31], currently associated with significant yield losses and extensive reliance on synthetic pesticides [32]. Experimental General All reagents were supplied by Sigma-Aldrich (Milan, Italy) and TCI (Tokyo, Japan) and were used without further purification unless

• then removed under reduced pressure. 1H NMR analysis of crude showed the presence of compound 5 with minor impurities coming from unreacted 1. Compound 5 was employed for the subsequent transformations without further purification. 1H NMR (500 MHz) δ 6.19 (s, 1H), 5.59 (s, 1H), 5.30 (brs, 1H), 4.30 (m

• ; HRESIMS (m/z): [M + Na]+ calcd for C32H46O4Na, 517.3294; found, 517.3298. Plant material, extraction, and purification of α-costic acid Whole aerial parts of Dittrichia viscosa plants were freshly collected in Algeria from naturally occurring populations. A voucher specimen was deposited at the herbarium

Amino acid-based surfactants: sustainable synthesis and antimicrobial mechanisms

• Rafaela Gomes Bezerra,
• Lourdes Pérez and
• Francisco Fábio Oliveira de Sousa

Beilstein J. Org. Chem. 2026, 22, 1067–1085, doi:10.3762/bjoc.22.85

• from moderate to high values depending on amino acid functionality, alkyl chain length, and purification strategy [10][37]. For structurally more complex surfactants, especially those derived from multifunctional amino acids such as lysine, arginine, and histidine, selective functionalization often

• large-scale applicability. Purification is commonly achieved by acid–base extraction, selective precipitation, salt formation, and crystallization, while chromatographic techniques are mainly restricted to laboratory-scale studies [38]. Scalable processes preferentially rely on phase separation and

• behavior and biological activity [58]. The synthesis of these molecules typically involves a two-step coupling process, often using geminal dihalides and functionalized amino acids. Nonetheless, some challenges such as by-product formation and high purification costs limit their scalability [75]. Despite

Synthesis of functionalized, 13-alkyl-substituted coralyne derivatives and investigation of their interactions with duplex and abasic site-containing DNA

• Laurin Beckmann,
• Jason Lennard Kunze,
• Hannah Karola Strunk,
• Maurice Michel and
• Heiko Ihmels

Beilstein J. Org. Chem. 2026, 22, 1057–1066, doi:10.3762/bjoc.22.84

• synthesized according to literature protocols. Papaverine (3a) was obtained by neutralization of papaverine hydrochloride [58]. Benzaldehyde was distilled under reduced pressure prior to use. Other reagents and other solvents were used without further purification. The buffer solutions were prepared from

One-pot four-component sequential synthesis of S-alkyl dithiocarbamates using lipase as a biocatalyst

• Mansour Shahedi,
• Pargol Tahmasebi pour and
• Zohreh Habibi

Beilstein J. Org. Chem. 2026, 22, 1048–1056, doi:10.3762/bjoc.22.83

• provide a useful basis for future studies directed toward medicinal, antifungal, and agrochemical applications. Experimental General remarks All reagents were commercially available and used without further purification. Solvents used for extraction and purification were distilled before use. Novozym 435

Synthesis of novel 1,2,4-oxadiazole-isoxazoline hybrids and their in silico potential with adenosine receptors

• Pshtiwan S. Mohammed,
• Mohammed K. S. Dalo,
• Onur C. Yazıcı,
• Muhammet Yildirim and
• Akın Sağırlı

Beilstein J. Org. Chem. 2026, 22, 1033–1047, doi:10.3762/bjoc.22.82

• purification by flash column chromatography using ethyl acetate/hexanes. Evaluation of the nitrile oxide cycloaddition results revealed that reactions involving p-chlorobenzaldoxime (2b), p-isopropylbenzaldoxime (2c), and p-tolylaldoxime (2f) proceeded with moderate to high efficiency, affording the

• conditions for reaction times ranging from 5 to 24 h. The corresponding 1,2,4-oxadiazolyl-diarylisoxazoline derivatives 7aa–ay were isolated in moderate to good yields after purification by flash column chromatography. The highest yield (97%) was obtained from the cycloaddition of p-bromobenzaldoxime (2g

Semisynthesis, characterisation, and antibacterial evaluation of a novel lecanoric acid-derived amide library

• Ethan D. Abbott,
• Sasha Hayes,
• Jonathan M. White,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2026, 22, 1023–1032, doi:10.3762/bjoc.22.81

• identified as a scaffold of interest for the generation of a unique semisynthetic biodiscovery screening library. Large-scale extraction and isolation on the Australian-sourced lichen Parmotrema tinctorum resulted in the purification of ≈1 g of the desired scaffold 1, along with other known lichen

• depside diffractaic acid yielded analogues with increased activity against a colorectal cancer stem cell [9]. Collectively, these promising results have inspired drug discovery researchers from around the world to pursue extraction, purification, characterisation, and bioactivity testing of lichen natural

• carboxylic acid moieties, which could all potentially serve as chemical handles for structural modifications via medicinal chemistry. Herein, we detail the large-scale extraction and purification of the targeted lichen natural product, lecanoric acid, along with the subsequent semisynthesis and

Synthesis and optical resolution of 4,5-diaminohomoadamantane: a promising scaffold for chiral ligands and bioactive compounds

• Polina A. Man’kova,
• Vadim A. Shiryaev,
• Olga S. Podlipnova,
• Marat M. Khisyamov,
• Dmitry S. Nikerov,
• Alexander N. Reznikov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2026, 22, 1013–1022, doi:10.3762/bjoc.22.80

• , homoadamantan-4-ene (2) was obtained from homoadamantan-4-ol (1). In 1969, a method for the preparation of alkene 2 from homoadamant-4-yl tosylate was proposed [85]. However, the formation of methyl tosylate and the need for purification of the product reduces its usefulness. We herein report an improved method

The role of spacer length and flexibility in peptide self-assembly

• Julian Link,
• Albin Lahu,
• Manfred Wagner,
• Tanja Weil and
• David Y. W. Ng

Beilstein J. Org. Chem. 2026, 22, 986–996, doi:10.3762/bjoc.22.77

• -yl)-1H,3H-benzo[de]isochromene-1,3-dione (2) with good yield (79%, Figures S1–S6 in Supporting Information File 1) after purification through recrystallization from ethanol [36]. Compound 2 was used as the precursor for the synthesis of the C6-/C3-, and C0-spacer building blocks 3, 4, and 5. To

• (C0-Nap, 5) was obtained from compound 2 and ʟ-isoleucine. The products were washed with 1 M HCl and brine and did not require further purification. The naphthalene imides 3, 4, and 5 were obtained with good yields (87–99%) and in high purities (90–95%) as characterized by liquid chromatography–mass

Synthesis of sterically shielded piperidine nitroxides via acid-catalyzed heterocyclization of β-aminoketone derivatives with ketones

• Mark M. Gulman,
• Yurii I. Glazachev and
• Sergey A. Dobrynin

Beilstein J. Org. Chem. 2026, 22, 948–954, doi:10.3762/bjoc.22.74

• using a sodium tungstate/hydrogen peroxide system. Attempted purification led to decomposition; therefore, crude 6a and 6b were used directly in the next step. It is known that the reaction of sterically hindered nitrones may lead to metalation or deoxygenation of the alkylnitrone group instead of

A practical CO₂-mediated synthesis of 5,6-carboxylated silicon-rhodamines for targeted probe development

• Dongjie Hou,
• Shaowei Wu,
• Ning Xu,
• Pengjun Bao,
• Wenhao Jia,
• Qinglong Qiao and
• Zhaochao Xu

Beilstein J. Org. Chem. 2026, 22, 915–924, doi:10.3762/bjoc.22.72

• readily available CO2, this method delivers carboxylated SiR derivatives in 60–93% yields while avoiding the use of t-BuLi, toxic CO, and expensive palladium catalysts. In addition, the crude carboxylation mixtures can be directly subjected to amide coupling without chromatographic purification, enabling

• ethyl acetate and concentrated before being directly subjected to amide coupling without chromatographic purification. To demonstrate the utility of this strategy for probe construction, we selected three representative SiR scaffolds 1a–c, which were widely used in super-resolution imaging, for direct

• carboxylation mixtures can be directly advanced to amide coupling without chromatographic purification, allowing streamlined one-pot construction of functionalized SiR probes. Using this approach, several high-performance probes were readily prepared and successfully applied to long-term live-cell super

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

• mass intensity (PMI). Reagents should be near-stoichiometric, purification steps minimal, and catalysts effective in substoichiometric quantities. Compatibility with one-pot system and automation, such as flow chemistry and robotic synthesis, further enhance scalability. Existing tools and techniques

• sortase A-protein Z system has limited site specificity; it also requires equimolar enzyme-to-antibody ratios and additional purification steps. MTG, similarly, requires near-stoichiometric enzyme to function, restricting scalability; this enzyme is also produced as a zymogen and requires activation post

• -purification, complicating the engineering workflow. PGA optimisation benefited from the simplicity of insulin, which contains only three primary amines whose labelling can be readily resolved by UPLC, but such strategies become impractical for larger, lysine-rich proteins. For a broader overview, Zhu et al

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

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

• -osaka, Osaka 577-0056, Japan 10.3762/bjoc.22.61 Abstract E-Selective bromination for diphenylacetylene was established by using the combination of NBS and FeBr3 in CH2Cl2. In addition, easy purification and separation from the crude product were found. When the crude product was treated with heptane

• , the E isomer could be recovered as a solid material by utilizing the difference in solubility. On the other hand, the Z isomer could be removed by filtration while remaining in solution. Keywords: bromination; diarylacetylenes; green chemistry; purification and separation; stereoselective reaction

• interested in the selective synthesis of the E isomer of 1,2-dibromo-1,2-diphenylethylene, together with simple purification and separation toward process chemistry, because the compound is an attractive synthetic intermediate for further transformations. During the course of our studies, we have found that

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

• ), which enabled the absolute configuration of 3 to be assigned as 7S,8R,7'S,8'R. Moreover, this is the first report of a crystal structure of (+)-eudesmin (3). In 2015, Lu et al. reported the purification and full characterization of both enantiomers of eudesmin from Acorus tatarinowii, along with the X

• (+)-pinoresinol (2, 113.5 mg, tR 41−42 min), which was preadsorbed to C18-bonded silica (≈1 g), packed into a guard cartridge, and subjected to semipreparative C18 HPLC purification. A linear gradient from 40% MeOH (0.1% TFA)/60% H2O (0.1% TFA) to 100% MeOH (0.1% TFA) over 50 min, followed by isocratic conditions

• (3.59) nm; ECD (MeOH) λext (Δε) 208 (+6.25), 256 (−0.08), 282 (+0.26) nm; see Supporting Information File 1 for 1H and 13C NMR data in CDCl3; LRESIMS m/z: [M + Na]+ 381, [M − H]− 357; HRESIMS m/z: [M + Na]+ calcd for C20H22NaO6, 381.1308; found, 381.1307. Preparation and purification of semisynthetic

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

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

• -butylammonium fluoride (TBAF) for TBS ether removal, followed by DMP for hydroxy group oxidation, delivering the desired product 1 in 29% overall yield in three steps from 14a/b, together with a double bond-isomerized product 15 in 39% overall yield after HPLC purification. The configuration of C12–C13 double

• conditions directly without further purification, affording cryptomeridiol (2) in 31% yield and 4-epi-cryptomeridiol (3) in 20% yield, respectively, in two steps from the expanded chiral pool germacrene A (5) produced by the engineered strain XT02019 harboring the IU pathway. The two diastereomers 2 and 3

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

• gases, which necessitate rigorous purification of the target products, particularly in the case of APIs. During the last 15 years, several strategies for efficient trifluoromethylation employing relatively inexpensive CF3 sources have been reported. These methodologies are based on UV-driven [7], metal

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

• solubility in MeCN/H2O systems used for preparative purification; the compounds dissolved only in DMSO, explaining the diminished recovery. Nevertheless, the synthetic route successfully delivered two structurally distinct CRBN-recruiting CK2 PROTACs. All synthesised PROTACs 23–26, 28, and 29 were evaluated

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

• . Purification by silica gel column chromatography eluting with EtOAc/hexane 5:95 provided azidol 7 [23] as slightly yellow oil (2.47 g, 14.77 mmol, 92%, lit. [23] 71%). 1H NMR (400 MHz, CDCl3) δ 5.69–5.61 (m, 1H), 5.60–5.52 (m, 1H), 3.79–3.65 (m, 2H), 2.56–2.36 (m, 2H), 2.27–2.09 (m, 4H), 1.81–1.67 (m, 2H); 13C

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

• 5 (CAS: 59582-20-6) [20] as a beige colored viscous oil, which was used without further purification. HRESIMS m/z: [M + H]+ calcd. for C18H23O4, 303.1591; found, 303.1596. 1H NMR data in CDCl3 (δ ppm) 1.43 (s, 3H, 2-CH3), 1.56 (s, 3H, 4’-CH3), 1.67 (s, 3H, 4’-CH3), 1.70/1.85 (m, 2H, H-2’), 2.10/2.15

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

• -workers assembled 276 via simple ring opening of 275`s oxetane moiety and no cooling and intermediate purification were necessary. These practical improvements are particularly important for the large-scale synthesis of 1. Furthermore, every step up to 292 was carried out in kg amounts using only

Structural reassignment of compound 968, an allosteric glutaminase inhibitor

• Lindsey A. Albertelli,
• Sainabou Jallow,
• Chun Li and
• Scott M. Ulrich

Beilstein J. Org. Chem. 2026, 22, 455–460, doi:10.3762/bjoc.22.33

• diffractometer. Nuclear magnetic resonance spectra were recorded on a JEOL ECX400 spectrometer. Glutaminase assays were measured on a Tecan Infinite M nano spectrophotometer. Reagents and solvents for chemical synthesis were used without additional purification. Chemical synthesis 3-Bromo-4

• employed for the final data presentation and structure plots [35]. The crystal data have been deposited in the Cambridge Crystallographic Data Centre, deposition number CCDC 2426481. Enzymatic assay Expression and purification of the GAC isoform of GLS1 Overnight cultures of BL21(DE3) strains carrying GAC