Harnessing tethered nitreniums for diastereoselective amino-sulfonoxylation of alkenes

• Shyam Sathyamoorthi,
• Appasaheb K. Nirpal,
• Dnyaneshwar A. Gorve and
• Steven P. Kelley

Beilstein J. Org. Chem. 2025, 21, 947–954, doi:10.3762/bjoc.21.78

• and only used commercial I(III) reagents and sulfonic acids. The products were quite stable in the reaction conditions and withstood standard purification protocols. No special precautions were taken to exclude air or ambient moisture, and the products were amenable to further transformations. We

4-(1-Methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones: synthesis, anti-inflammatory effect and in silico approaches

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Luc Van Meervelt,
• Do Thi Thao and
• Nguyen Minh Thong

Beilstein J. Org. Chem. 2025, 21, 817–829, doi:10.3762/bjoc.21.65

• further purification. For column chromatography, 70–230 mesh silica 60 (E. M. Merck) was used as the stationary phase. Electrospray ionization–high-resolution mass spectra (ESI–HRMS) were acquired on a SCIEX X500 QTOF instrument in the positive ion mode. A Büchi melting point B-545 apparatus was used to

Synthesis and photoinduced switching properties of C₇-heteroatom containing push–pull norbornadiene derivatives

• Daniel Krappmann and
• Andreas Hirsch

Beilstein J. Org. Chem. 2025, 21, 807–816, doi:10.3762/bjoc.21.64

• were observed. However, purification was not possible. Furthermore, an alternative commonly used synthetic strategy involving the Diels–Alder reaction of a pre-functionalized push–pull acetylene with furan or pyrrol derivatives proved unsuccessful [4][43]. All synthesized NBD derivatives were

Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• used it after isolation and characterization. In these cases, BINOL phosphate 5 was purchased, and used either without any further purification (Table 2, entries 5–7), or it was washed first with 2 N HCl solution, then rinsed with water, to remove possible traces of Ca2+, which could stem from

• source and purification of ligand 5, are varied, showed that these parameters strongly influence the hydrocyanation enantioselectivity. In order to elucidate the mechanism of action of the pre-catalyst complex 6 and to explain the observed low enantioselectivity, we have carried out DFT computations with

Copper-catalyzed domino cyclization of anilines and cyclobutanone oxime: a scalable and versatile route to spirotetrahydroquinoline derivatives

• Qingqing Jiang,
• Xinyi Lei,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2025, 21, 749–754, doi:10.3762/bjoc.21.58

• ) trifluoroacetate (Cu(TFA)2) as the catalyst (20 mol %) under ambient air at 80 °C for 12 hours; the product 3aa was isolated by chromatographic purification (Table 1, entry 1). The use of other solvents, including acetonitrile (MeCN), tetrahydrofuran (THF), toluene, acetone and methanol (MeOH), resulted in

Synthesis of HBC fluorophores with an electrophilic handle for covalent attachment to Pepper RNA

• Raphael Bereiter and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 727–735, doi:10.3762/bjoc.21.56

• usefulness of this type of bifunctional fluorescent ligands in RNA affinity purification has recently been demonstrated by our group [11]. Conclusion Covalent fluorescent light-up aptamers (coFLAPs) are opening new avenues for RNA imaging [11]. In this work, we describe robust synthetic routes for twelve HBC

• . Chemical reagents and solvents were purchased in the highest available quality from commercial suppliers (Merck/Sigma-Aldrich, ABCR) and used without further purification. Analytical thin-layer chromatography (TLC) was performed on Macherey-Nagel Polygram® SIL G/UV254 plates. 0.2 mm silica gel 60 for

Acyclic cucurbit[n]uril bearing alkyl sulfate ionic groups

• Christian Akakpo,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 717–726, doi:10.3762/bjoc.21.55

• used without further purification. Guest molecules were available from previous studies [65][71]. Compounds TetW1OAc and TetW1 were prepared according to the literature procedures with slight modifications [70]. NMR spectra were recorded using commercial spectrometers operating at 600 or 400 MHz for 1H

Photochemically assisted synthesis of phenacenes fluorinated at the terminal benzene rings and their electronic spectra

• Yuuki Ishii,
• Minoru Yamaji,
• Fumito Tani,
• Kenta Goto,
• Yoshihiro Kubozono and
• Hideki Okamoto

Beilstein J. Org. Chem. 2025, 21, 670–679, doi:10.3762/bjoc.21.53

• common organic solvents. Therefore, the crude 18 was subjected to the Mallory photoreaction without purification. Photoirradiation of diarylethene 18 was performed in the presence of a catalytic amount of I2 in refluxing toluene to afford F87PHEN which was isolated by sublimation under vacuum. Absorption

Asymmetric synthesis of fluorinated derivatives of aromatic and γ-branched amino acids via a chiral Ni(II) complex

• Maurizio Iannuzzi,
• Thomas Hohmann,
• Michael Dyrks,
• Kilian Haoues,
• Katarzyna Salamon-Krokosz and
• Beate Koksch

Beilstein J. Org. Chem. 2025, 21, 659–669, doi:10.3762/bjoc.21.52

• several chromatographic purification steps (EtOAc/n-pentane, 2% AcOH). Hence, in the here described case, the final hydrolysis and Fmoc protection resulted the enantiomerically pure isomer Fmoc-(2S,4R)-TfLeu (12a), isolated in a good yield of 40% and with excellent enantiomeric purity of 97% ee. The

• chemicals were used without further purification and obtained from commercial sources. Synthesized compounds 3,3,3-Trifluoro-2-methylpropyl 4-methylbenzene-1-sulfonate (9): 8 (5.00 g, 39.0 mmol, 1.0 equiv), was dissolved in DCM (48.8 mL). p-Toluenesulfonyl chloride (11.15 g, 58.5 mmol, 1.5 equiv) and DMAP

• purification. 1H NMR (600 MHz, CDCl3) δ 8.88 (d, J = 2.2 Hz, 1H), 8.07 (d, J = 9.3 Hz, 1H), 7.79 (dd, J = 8.2, 2.2 Hz, 1H), 7.62 (p, J = 5.7 Hz, 2H), 7.49 (dt, J = 9.0, 4.4 Hz, 1H), 7.37 (d, J = 8.1 Hz, 1H), 7.33 (dt, J = 6.3, 2.0 Hz, 1H), 7.15 (dd, J = 9.3, 2.8 Hz, 1H), 6.88 (d, J = 7.7 Hz, 1H), 6.63 (d, J

Semisynthetic derivatives of massarilactone D with cytotoxic and nematicidal activities

• Rémy B. Teponno,
• Sara R. Noumeur and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 607–615, doi:10.3762/bjoc.21.48

• each as white powder after HPLC purification of the mixture formed from reaction of massarilactone D with cinnamoyl chloride in triethylamine in the presence of catalytic amounts of 4-dimethylaminopyridine. The ESIMS of compound 3 exhibited the sodium adducts at m/z 507.20 [M + Na]+ and 991.39 [2M + Na

Sequential two-step, one-pot microwave-assisted Urech synthesis of 5-monosubstituted hydantoins from L-amino acids in water

• Wei-Jin Chang,
• Sook Yee Liew,
• Thomas Kurz and
• Siow-Ping Tan

Beilstein J. Org. Chem. 2025, 21, 596–600, doi:10.3762/bjoc.21.46

• ,f) often precipitated out of the reaction mixture and were sufficiently pure (>95% by HPLC) after the simple washing steps, and the more polar hydantoin products could be extracted out of the reaction mixture with ethyl acetate and did not require further chromatographic purification. The “one-pot

• of this process is promising, driven by its simplicity, moderate to high yields, and the use of environmentally friendly reagents. Notably, microwave-assisted one-pot reactions eliminate the need for column chromatography, a common step in traditional purification methods but limits scalability

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• implementation often implies fewer purification steps to achieve the target molecules, leading to a reduction of waste, when compared to traditional “step by step” synthesis. Another advantage of MCRs is that by selecting appropriate starting materials, follow-up functionalization by, e.g., post-cyclization of

• [17][18]. An important drawback of this solvent is the difficulty of its removal from the reaction crude, and extractions with water are commonly employed before purification. Depending on the reaction conditions, DMSO can be transformed into different products, e.g., under redox conditions, DMSO can

• either of the two nucleophilic nitrogen atoms present in the amidine component, thus leading to the production of both regioisomers 42a and 42b and therefore to a demanding purification process (Scheme 33). To avoid these drawbacks, Lyon et al. optimized the reaction by using free monohydrated glyoxylic

Unprecedented visible light-initiated topochemical [2 + 2] cycloaddition in a functionalized bimane dye

• Metodej Dvoracek,
• Brendan Twamley,
• Mathias O. Senge and
• Mikhail A. Filatov

Beilstein J. Org. Chem. 2025, 21, 500–509, doi:10.3762/bjoc.21.37

• purification, the 1H NMR of Cl2B showed 6% of an impurity, possibly the anti-isomer. Further purification of Cl2B reduced the impurity content to less than 3%. Topochemical photocycloaddition Upon examining the crystal structure of our first sample of Cl2B, Cl2B (A), we observed that the compound had undergone

• packing mode. Extra precautions were taken to shield the compounds from light during synthesis, purification, and storage. After crystallizing each bimane, a vial containing multiple crystals was selected for irradiation studies. Cl2B (B), which showed 5% presence of the [2 + 2] dimer after

Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• protecting groups and time-consuming purification steps, that provides preQ1 in 43% overall yield with a purity of >98% (Scheme 2). The approach is based on the cyclocondensation reaction between 2-chloro-3-cyanopropan-1-al (6) (itself obtained from chloroacetonitrile and methyl formate) and 2,6

• novel 2,6-diamino preQ1 analog 2 (DPQ1) by hydrogenation of 8 (DPQ0 [32]) (Scheme 2). In this case, however, a final purification step (by reversed-phase chromatography) was required. Notably, using the hydrogenation conditions described here, we were also able to streamline our previously reported 7

• mild reduction with methanolic sodium borohydride. Upon purification by reversed-phase chromatography using aqueous hydrobromic acid as eluent (0.5% in H2O), a considerable fraction of the alcohols was already converted to the desired bromides 4c,d. Only in the case of 4b, no deoxygenative bromination

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• described in the literature (Scheme 5) [41][42]. Treatment of a 3:1 mixture of the anti/syn-diastereoisomers of compound 3 with 1,3-propane dithiol in the presence of a small amount of scandium triflate [43] afforded compound 18, which was used in the next step without further purification. Hydrogenolysis

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• purification possibilities available for robust organic cages mean access to structural families via stepwise synthesis or statistical methods followed by separation is facile, as demonstrated by Otte [42][43][44] and ourselves [41]. The lack of internal functionality in cavities doesn’t just reduce the

Identification and removal of a cryptic impurity in pomalidomide-PEG based PROTAC

• Bingnan Wang,
• Yong Lu and
• Chuo Chen

Beilstein J. Org. Chem. 2025, 21, 407–411, doi:10.3762/bjoc.21.28

• to generate an inseparable byproduct. By contrast, the byproduct derived from Boc-protected amines has a significantly different retention time on HPLC and could be removed by regular silica gel chromatography. Because the formation of 5‒7 posts a significant purification challenge, we sought to

• generally modest, it remains highly popular because of the convenience and the modularity of this method. When reacting 1 with an amino-PEG-OH, the purification of the reaction mixture is particularly difficult as a major byproduct co-elutes with the desired product even on HPLC. Importantly, the impurity

• sulfonate to the byproduct by reacting it with taurine allows for easy decontamination. This method may facilitate the purification of other similar reactions and improve the quality of related pomalidomide derivatives. The structures of veliparib and iVeliparib-AP6. Identification of the cryptic impurity

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• , usually proteins or lipids by the process of glycosylation producing glycoproteins or glycolipids, respectively. Nature executes these processes by enzymatic pathways [18] and is often flawless in its desired output. But the scarcity and the cumbersome purification of natural enzymes limit the use of

• in attaining the required stereospecific glycosylation outputs. Apart from the widely convenient stepwise synthesis, recently one-pot glycosylations have also made an important mark which minimise the tedious purification of the intermediate molecules in each step [53][54][55][56][57][58]. In the

Synthesis, characterization, antimicrobial, cytotoxic and carbonic anhydrase inhibition activities of multifunctional pyrazolo-1,2-benzothiazine acetamides

• Ayesha Saeed,
• Shahana Ehsan,
• Muhammad Zia-ur-Rehman,
• Erin M. Marshall,
• Sandra Loesgen,
• Abdus Saleem,
• Simone Giovannuzzi and
• Claudiu T. Supuran

Beilstein J. Org. Chem. 2025, 21, 348–357, doi:10.3762/bjoc.21.25

• ) with Ki values of 82.6 and 88.4 µM, respectively. Experimental All solvents were used after double distillation. Other chemicals involved in synthesis were procured from Sigma-Aldrich and Alfa Aesar and used without further purification. Melting temperatures of all the synthesized compounds were noted

Antibiofilm and cytotoxic metabolites from the entomopathogenic fungus Samsoniella aurantia

• Rita Toshe,
• Syeda J. Khalid,
• Blondelle Matio Kemkuignou,
• Esteban Charria-Girón,
• Paul Eckhardt,
• Birthe Sandargo,
• Kunlapat Nuchthien,
• J. Jennifer Luangsa-ard,
• Till Opatz,
• Hedda Schrey,
• Sherif S. Ebada and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 327–339, doi:10.3762/bjoc.21.23

• phase consisted of deionized water (H2O) + 0.1% formic acid as solvent A and MeCN + 0.1% formic acid as solvent B. The flow rate was set at 30 mL/min for fractions 3, 4, and 8, and 20 mL/min for fraction 6. The collected fraction volume for each run was 15 mL. In the purification of fraction 3 (1,315 mg

• ), a gradient elution was implemented, starting from 60% B and progressing to 100% B in 30 minutes. The gradient was then held at 100% B for 10 minutes, resulting in the isolation of 6 (30 mg, tR = 34 min). For the purification of fraction 4 (306 mg), a gradient elution was applied, transitioning

• solvent B from 30% to 100% over 85 minutes. Subsequently, it was maintained at 100% for 15 minutes. This purification protocol led to the isolation of 1 (9.1 mg, tR = 67 min), 3 (19.5 mg, tR = 81 min), and 5 (2.8 mg, tR = 89 min). For fraction 6 (489 mg), a gradient elution was applied starting from 50% B

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• -hydroxyacetophenone and N,N-dimethylformamide dimethyl acetal (DMF-DMA) were reacted at 120 °C to give compound 3a, and without further isolation and purification, 1a, H2SO4 and TBAI were added directly to the reaction solution and the reaction was continued at 120 °C for 12 hours. In this way, the product 4a could

Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• JMS-T100GCV or a JEOL JMS-T200GC spectrometer. All the reactions were conducted under argon or nitrogen. Materials: Column chromatography was conducted on silica gel (Silica Gel 60 N, Kanto Chemical Co., Inc.). Toluene and N,N-dimethylformamide (DMF) were purified by a solvent-purification system

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• substituted β-nitrostyrenes. This one-pot procedure allows the quick isolation of substituted β-nitrostyrene scaffolds with 62–83% yield under mild conditions, without the need for special precautions, inert atmosphere, and time-consuming purification techniques. Keywords: 2C-X; CuCl2; NaBH4; β-nitrostyrene

• atmosphere, special precautions, and with isolated yields up to 60% [14][15]. Due to the formation of side products, final purification of the amino derivatives requires the use of either multiple separation techniques, chromatography, or distillation [15][16][17][18] (Scheme 1). Differently from lithium

• MassLynx ver. 4.1 and data analysis was done using Waters OpenLynx browser ver. 4.1. Solvents were commercial HPLC grade and used without further purification. The substrates 2a, 7a, and 8a were commercially available and used without further purification. The substituted β-nitrostyrenes 1a and 3a–6a were

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• , involving the setup of the reaction, mixing of reactants, reaction workup, product analysis, and product purification. To perform all these basic chemistry tasks effectively, customizable HTE platforms are available from various laboratory instrument manufacturers or can be assembled using a mix of

• perform most tasks in chemical and material synthesis, the hardware currently cannot perform product purification and multistep synthesis continuously. HTE using flow platforms Flow reactions are characterized by a constant flow of reagents and products into and out of the reaction vessel. A flow platform

• products once experiments are performed. Despite this bottleneck, the landscape is evolving, with various practical tools emerging to streamline purification processes. From prepacked silica gel tubes to the precision semipreparative liquid chromatography and the versatile capabilities of various scavenger

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• HPLC (RP-HPLC), which led to the purification of the known metabolites, ianthelliformisamines A–C (1–3) [7] and aplysterol (8) [13], and four new natural products, ianthelliformisamines D–G (4–7) (Figure 1). This extraction and isolation process was repeated twice to obtain sufficient quantities of the

• contained mixtures of polyamine-type alkaloids, which were combined for further isolation work. The following describes the purification of these fractions. Fractions 34–35 (5.0 mg) were purified by semipreparative phenyl RP-HPLC using isocratic conditions of 70% H2O (0.1% TFA)/30% MeOH (0.1% TFA) for the

• first 10 min, then a linear gradient to 10% H2O (0.1% TFA)/90% MeOH (0.1% TFA) was run over 50 min at a flowrate of 9 mL/min; 60 fractions (60 × 1 min) were collected and resulted in the purification of ianthelliformisamine A (1, 1.0 mg, tR 16 min, 0.010% dry wt). Fractions 38–40 were combined (45.0 mg