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

• containing potassium and magnesium ions at a physiological pH of 7.0 for 5 hours. Analysis of the reaction mixture by anion-exchange HPLC revealed that the bromopropyl handle (C3 homolog 8) gave the highest yield of covalently tethered HBC-RNA complex (50%). Significantly less RNA alkylation yield was

• in 40 µL of water, followed by the addition of 12 µL of buffer (250 mM HEPES, 500 mM KCl, pH 7.0) and 6.0 µL of MgCl2 solution (20 mM). The aptamer was annealed by heat shock at 90 °C for 2 minutes and cooled on ice. Then, 2.0 µL of a ligand stock solution (3.0 mM, in DMSO) was added. The final

• analyzed by AE chromatography (Dionex DNAPac PA-100 column; 4 mm × 250 mm) at 80 °C with a flow rate of 1.0 mL/min. A gradient of 25–37.5% B in A in 25.0 minutes was used; Eluent A: 25 mM Tris∙HCl, 10 mM NaClO4, 20% acetonitrile, pH 8.0; eluent B: 25 mM Tris∙HCl, 600 mM NaClO4, 20% acetonitrile, pH 8.0

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

• JEOL AccuTOF electrospray instrument. ITC data was collected on a Malvern Microcal PEAQ-ITC instrument with a cell volume of 200 µL and an injection syringe with a capacity of 40 μL. For ITC experiments, the host and guest solutions were prepared in a 20 mM phosphate-buffered water (pH 7.4). The sample

• %; c) dry pyridine, pyridine sulfur trioxide complex (20 equiv), 90 °C, 18 h, 68%. Thermodynamic parameters (Ka (M−1), ∆H° (kcal/mol) determined for the C1·guest, M1·guest and M0·guest complexes by ITC. Conditions: 298.0 K, phosphate-buffered saline, pH 7.4. Supporting Information The X-ray crystal

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• pendant aryl moiety, is better for target-binding and hence 41 is a ≈10-fold more potent inhibitor of BACE-1 than 40. Several further examples of cyclic ethers will be examined in section 5 (sugars). The anomeric effect applies in acyclic ethers, too. Consider the non-fluorinated scaffold, Ph–O–CH3 (42

• neutral pH, and the partially negative fluorine atom (I, Figure 11) [96]. This attraction has the outcome of favouring a gauche F–C–C–N+ alignment. This gauche alignment can be further stabilised by two additional interactions: hyperconjugation (II, Figure 11) [148], and intramolecular hydrogen bonding

• ][179][180][181]. For example, consider the analgesic drug fentanyl (104, Figure 11). This drug contains a piperidine moiety, which is protonated at physiological pH and forms a salt bridge with an aspartate residue in the binding site of the μ-opioid receptor. One of the drawbacks of fentanyl (104) is

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

• filtrate, MeCN (18.5 mL) and EDTA-Na2 (3.45 g, 9.26 mmol, 1.0 equiv) were added and the reaction mixture was stirred at room temperature for 2 h. Subsequently, the solution was treated with aq NaOH (18 M) to pH 7 and Na2CO3 (1.96 g, 18.5 mmol, 2.0 equiv) was added. FmocOSu (3.12 g, 9.26 mmol, 1.0 equiv

• ) was dissolved in acetone (37.0 mL) and added dropwise to the reaction mixture. After 17 h of stirring at room temperature, MeCN and acetone were removed under reduced pressure, H2O (40 mL) was added, and the mixture was treated with aq HCl (6 M) to pH 2. The resulting solution was extracted with EtOAc

• treated with aq NaOH (18 M) to pH 7 and Na2CO3 (2.71 g, 25.6 mmol, 2.0 equiv) was added. FmocOSu (4.32 g, 12.8 mmol, 1.0 equiv) was dissolved in acetone (51.2 mL) and added dropwise to the reaction mixture. After 17 h of stirring at room temperature, MeCN and acetone were removed under reduced pressure

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• dependent on both the leaving group of the allylic electrophile and the choice of the supporting ligand. When (+)-1,2-bis{(2S,5S)-2,5-diphenylphospholano}ethane {(S,S)-Ph-BPE} (L1) was employed as the supporting chiral ligand, initially allylic chloride was found to provide the desired product 32 with

• excellent enantioselectivity, although in moderate yield. Notably, the presence of a chloride anion in the reaction mixture proved crucial for high enantioselectivity, leading to the discovery that a 1:1 complex of copper(I) chloride and (S,S)-Ph-BPE (L1) could serve as an optimal catalyst system. Further

• phosphate. The absolute stereochemistry of the products was found to be consistent with that of previously reported CuH-catalyzed transformations using (S,S)-Ph-BPE (L1) as the supporting ligand, suggesting a common mode of stereoinduction. In parallel, Hoveyda and co-workers demonstrated the first copper

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• to modify them. Reactions must be carried out at or near ambient temperatures and near-neutral pH. Aqueous media is often required to solubilize the substrates and/or to prevent denaturation, and reactions are normally carried out under very dilute (micromolar) conditions. As importantly, the highly

• for the types of reactions that can be used for the elaboration of ADCs. Among the signature features of photochemical, single-electron transformations is their ability to be conducted in dilute aqueous media at room temperature and at neutral pH [47]. Additionally, the distinctive mechanistic

• conditions can lead to denaturation, aggregation, or loss of functionality. Buffers, which are commonly used to stabilize antibodies by maintaining their pH and ionic strength, must also be compatible with the photoredox process to prevent unwanted side reactions or instability. Thus, although photoredox

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

• extract, pH 6.3) by the endophytic fungus Dendrothyrium variisporum. This fungus, isolated from the roots of the Algerian plant Globularia alypum, was explored for the first time for its potential to produce secondary metabolites [16]. Despite the abundant production of massarilactone D, it did not

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

• mixture was neutralized to pH 7 using saturated sodium bicarbonate solution and extracted with ethyl acetate multiple times. The organic extracts were combined, dried with anhydrous sodium sulfate, and concentrated under reduced pressure to afford H2d as a white solid. Yield 70%. 1H NMR (400 MHz, DMSO-d6

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

• containing a PH bond adds to the C=N bond of a preformed imine 30, while in the three-component Kabachnik–Fields reaction, the imine, which is generated in situ from a carbonyl compound and an amine, reacts with the dialkyl phosphite to produce the desired α-aminophosphonates 32 (Scheme 25) [72][74]. This

Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• control of equivalents and pH, or Leuckart–Wallach-like reaction with ammonium formate and Pd/C [25] provided monomethylaniline 7 in 37% and 35% yield, respectively. The absolute structure of monomethylaniline 7 was confirmed by single-crystal X-ray diffraction measurements (Figure 2). Compound 7

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

• compounds capable of undergoing topochemical [2 + 2] cycloaddition reactions initiated by visible light. A number of related bimane structures have been reported. These include anti-(Ph,Cl)bimane (CPDZBO10) where the Ph residues impart a bowl-shaped bimane distortion and syn-(Ph,Cl)bimane [25], anti-(H,Me

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• diazocines 13 and 21 were also investigated in aqueous solution (13 and 21 in aqueous PBS buffer solution at pH 7.4 250 µM, 21 at pH 3.5 250 µM, 13 at pH 9 250 µM). Benzoic acid derivative 13 was representatively chosen for polar aromatic substitution and the amino derivative 21 for non-aromatic substitution

• . Non- or less polar aromatic substituents were not characterized in detail since their solubility in pure water is decreased by the additional phenyl substituent. The pH values were chosen to make sure that the amine 21 is completely protonated and the carboxylic acid 13 is completely deprotonated. UV

• measurements revealed that the absorption maxima of the n–π*-transitions of the Z isomers of 13 and 21 (392–398 nm) are almost independent of solvent and pH, while the n–π*-transitions of the E isomers at ≈515 nm are significantly shifted to shorter wavelengths (Δλmax = 10–20 nm) in water (Table 7). At the

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

• File 1; compounds 3a, 4b–d, 11, and 12). If insolubles were present after pH 1–2 was reached, the suspension was filtered. Purification is described in Supporting Information File 1 for the individual compounds 3a, 4b–d, 11, and 12. A) Chemical structures of hypermodified nucleobase queuine and

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

• -functionalized aldehydes with at least one stereocenter in the C3 position. The results, which are collected in Table 5, show that the kinetic resolution depends on the characteristics of the substituents. The best results were achieved for the Michael adduct 12, derived from acetylacetone, with R1 = Ph (entry

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

• -2 position of glycosyl donors which can contribute towards 1,2-trans glycosylations without affecting the reactivity of the donor. They introduced carbamate ester moieties as alternative protecting groups. The N-phenylcarbamoyl (PhCar) moiety showed high stability in the pH range of 1–12 and it

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• enantioenriched nitrile products 29. The proposed mechanism is illustrated in Figure 8. [Mes-Acr-Ph]+* is generated through the photoexcitation of the photocatalyst [Mes-Acr-Ph]+, which undergoes electron transfer to the heteroarene 28, resulting in the formation of the [Mes-Acr-Ph]• and heteroarene radical

• cation 30. The [Mes-Acr-Ph]• is regenerated to the ground-state acridinium [Mes-Acr-Ph]+ through a single oxidation step on the anode, and the heteroarene radical cation 30 then reacts with the arylalkene 27 to form a benzylic radical intermediate 31. The benzylic radical intermediate 31 is subsequently

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

Synthesis, characterization, and photophysical properties of novel 9‑phenyl-9-phosphafluorene oxide derivatives

• Shuxian Qiu,
• Duan Dong,
• Jiahui Li,
• Huiting Wen,
• Jinpeng Li,
• Yu Yang,
• Shengxian Zhai and
• Xingyuan Gao

Beilstein J. Org. Chem. 2024, 20, 3299–3305, doi:10.3762/bjoc.20.274

• redshifts are observed for 7-Ph-1 (λmax = 354 nm) and 7-Ph-2 (λmax = 366 nm). In contrast to 7-H, 7-Br (λmax = 327 nm) and 7-Cz-1 (λmax = 316 nm) show a blueshift. With a stronger electron-donating ability than 7-Cz-1, 7-Cz-2 shows a lower energy level for the absorption band stemming from intramolecular

• donor carbazole group (Figure 3a). Compared to 7-H (λem = 408 nm, Table 2), compounds 7-t-Bu (λem = 424 nm), 7-Cz-1 (λem = 436 nm), 7-Cz-2 (λem = 444 nm), and 7-Ph-1 (λem = 425 nm) all show a redshift due to the electron-donating groups (t-Bu, Cz, Ph) on the carbazole moiety. However, 7-Ph-2 exhibits a

Efficient synthesis of fluorinated triphenylenes with enhanced arene–perfluoroarene interactions in columnar mesophases

• Yang Chen,
• Jiao He,
• Hang Lin,
• Hai-Feng Wang,
• Ping Hu,
• Bi-Qin Wang,
• Ke-Qing Zhao and
• Bertrand Donnio

Beilstein J. Org. Chem. 2024, 20, 3263–3273, doi:10.3762/bjoc.20.270

• variety of triphenylene derivatives (Figure 1) [44][45][46][47] based on the nucleophilic substitution of various electrophilic perfluoroarenes, including C6F2H4, C6F6, C10F8, and C6F5-Ph, by nucleophilic organolithium reagents. e.g., 2,2’-dilithio-4,4’,5,5’-tetrakis(alkoxy)-1,1’-biphenyls, 2Li-BPn

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• their aggregates. Moyano, Crusats and co-workers have done an extensive work on the development of supramolecular organocatalysts containing an amphiphilic metal-free porphyrin meso-(4-sulfonatophenyl)porphyrin and its J-aggregates [67][68][69][70]. In acidic (pH < 4.8) aqueous solutions, the central

• or achiral cyclic secondary amine moieties oscillate between the aggregated and non-aggregated state depending on pH (Figure 11). The diprotonated species generated at lower pH forms supramolecular aggregates whereas the metal-free macrocycle is unable to aggregate and remains in the solution as a

• monomer. Since the aggregates were found catalytically inactive, while the monomers in the solution were active, the system acts as a pH-switchable ‘ON–OFF’ organocatalyst. In the case of the enamine-mediated addition of cyclohexanone (62) to 4-nitrobenzaldehyde (7), using 10 mol % of 58 provided up to 99

Investigation of a bimetallic terbium(III)/copper(II) chemosensor for the detection of aqueous hydrogen sulfide

• Parvathy Mini,
• Michael R. Grace,
• Genevieve H. Dennison and
• Kellie L. Tuck

Beilstein J. Org. Chem. 2024, 20, 2818–2826, doi:10.3762/bjoc.20.237

• − in the aqueous state at a pH of 7.4 due to its weak acidic nature and high solubility in water (80 mM at 37 °C) [6]. Elevated levels of H2S in groundwater pose high risks to both human health and aquatic ecosystems [7], compelling rigorous monitoring of water sources. Even though sensors for

• ). Response of Tb.1 with Cu2+ ions The addition of excess Cu2+ ions to Tb.1 was expected to result in complete saturation of emission signals. However, upon the titration of Cu2+ ions to 5 μM Tb.1 (10 mM Tris-HCl buffer containing 5% DMSO, pH 7.4), emission signal saturation was not observed until 5

• containing 5% DMSO, pH 7.4 was used (Figure S4 in Supporting Information File 1), with a similar degree of quenching to that observed in 10 mM Tris-HCl buffer. The incomplete quenching in luminescence was previously also observed for the Eu(III)/Cu(II) complex [16]. Supramolecular.org [18], an Open Access

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• porphyrins, achieved porphyrins 32 and 33 in a 47% and 56% yield, respectively (Table 1, entries 13 and 21), using Cs2CO3 as the base. Electron-withdrawing sulfur-containing heterocyclic substrates 21 and 23 do not readily undergo protodeboronation even at high pH [44][47] making the yields of porphyrins 31

• explored, or further changes in the pH of the solution. Enrichment to the αβαβ-atropisomer may also be favorable [50], as to alleviate the steric hindrance caused by the short distances (4.3–4.4 Å) between bromines in the α2β2-atropisomers (cf., Figure 5). Borylation and further coupling of

• was synthesized through classic C–C coupling reactions at the meso-phenyl position. It was found varying temperature and the pH of the solution are effective mitigations to overcome unfavorable reaction electronics or demanding sterics presented at the meso-phenyls’ meta- or para-position

Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• ] 3. Based on our experience on the use of graphene oxide (GO) as heterogeneous catalyst to promote MCRs and subsequent C–N bond oxidation [16][21], we first investigated the GO-promoted oxidation of N-Ph-THIQ and the subsequent 3C Ugi reaction to give α-aminoamidine 2a. Applying the previously

• synthetic process in a one-pot manner, adding all the components from the very beginning. So, the blue-light-promoted reaction between N-Ph-THIQ, 3-methoxyaniline and tert-butyl isocyanide in the presence of BrCCl3 was extensively optimized by varying several parameters, such as solvent, relative quantity

• α-aminoamidines 2a, while the spiro-compound 3a was the main product. 3a was the result of a four-step one-pot process where an oxidation of N-Ph-THIQ, a 3C Ugi-type reaction, a second oxidation of the Ugi-type product 2a and a final cyclization took place, as we had initially planned. Excited by

Applications of microscopy and small angle scattering techniques for the characterisation of supramolecular gels

• Connor R. M. MacDonald and
• Emily R. Draper

Beilstein J. Org. Chem. 2024, 20, 2608–2634, doi:10.3762/bjoc.20.220

Efficient modification of peroxydisulfate oxidation reactions of nitrogen-containing heterocycles 6-methyluracil and pyridine

• Alfiya R. Gimadieva,
• Yuliya Z. Khazimullina,
• Aigiza A. Gilimkhanova and
• Akhat G. Mustafin

Beilstein J. Org. Chem. 2024, 20, 2599–2607, doi:10.3762/bjoc.20.219

• mixture to room temperature, concentrated H2SO4 was slowly added until pH 6–7 according to litmus paper and left standing for 12 h. The precipitated white crystals were filtered off, washed with water, and dried in air. Compound 2 yields are given in [13] and compound 5 yields are given in Table 1. b

• temperature, concentrated H2SO4 was slowly added until pH 6–7 according to litmus paper and left standing overnight (12 h). The precipitated crystals were filtered off, washed with water, acetone, and dried in air. The crude product was recrystallized from water with activated carbon. The yield of compound 2

• H2SO4 was added and the reaction mixture was stirred at the same temperature for 1 h and cooled. The precipitated crystals were filtered off, washed with cold distilled water to pH 6–7 (2 × 5 mL), and recrystallized from ethanol. 5-Hydroxy-6-methyluracil (3). Yield 98%. The spectral characteristics are