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

• (NGP) to control the 1,2-trans selectivity of the glycoside product. Torikai et al. developed a wide range of alkoxymethyl derivatives for directing the stereochemical outcome of the glycosylation reactions. The most significant of the protections include methoxymethyl (MOM) [140], benzyloxymethyl (BOM

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• experimental samples compared to control samples [39]. A431 and H1299 cells were seeded into 96-well plates at 15000/well in DMEM medium supplemented with 10% EFV and cultured under standard conditions at 5.0% CO2 and 37 °C. The next day, the medium was replaced and test compound 7a was added in a series of

• two-fold dilutions from 0.12 μM to 120 μM. In the control wells, the medium was replaced without adding the compound 7a. The cells were then incubated under the same standard conditions for 24 h, after which the medium was replaced and 10% MTT solution in DMEM medium supplemented with 10% EFV was

• cytotoxic activity was determined by the change in optical density at 540 nm in wells treated with the compound 7a or cisplatin compared to control wells. The experiment was carried out in three biological replicates with 6 technical replicates in each. Results were analyzed using one-way ANOVA followed by

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

• prepared in DMSO and cancer cells were treated with 10 μM doses of compounds using the apoptosis inducing standard mensacarcin (10 μM) as a positive control [56]. Only compound 7l decreased cell viability to 63%, while the rest of the compounds showed very low to no significant decrease in cell viability

• microbroth single-dose assays. Dimethyl sulfoxide was used at a final concentration of 0.1% as negative control. Microbroth dilution assays [52] for the most potent bioactive compounds 7b and 7h were performed using nine serial dilutions of the tested compounds with final concentrations of 256, 128, 64, 32

• cells were treated with 10 μM doses of each compound and mensacarcin (10 μM) as a positive control [56]. MTT in 1X PBS was added for a final concentration of 0.5 mg/mL 48 hours post compound addition to each well. Post incubation at 37 °C was carried out for 2 h. After the removal of the growth media

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

• responses [1]. Biofilm-forming microbes were found to be up to 1,000 times more resistant to antibiotics than their planktonic forms [2]. According to the fact sheets of the National Institute of Health (NIH) and the Center for Disease Control and Prevention (CDC), 65 and 80% of all microbial and chronic

• (SKOV-3), epidermoid carcinoma (A431) and lung cancer (A-549) cell lines. Epothilone B served as the positive control. Following a 5 day incubation period, the minimum concentration required to achieve 50% growth inhibition (IC50 values) was determined. Biofilm inhibition sssay Biofilm inhibition

• (TPP Tissue Culture ref no. 92196) for 24 hours. Biofilm inhibition was measured using crystal violet (CV) staining, with methanol as the control and microporenic acid A as the positive control [21]. Error bars indicate SD with duplicates in two biological repeats (n = 4). Biofilm dispersal assay

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• -red region, providing excellent control over molecular weight and polydispersity in the polymerization of various monomers, including methyl acrylate. The authors highlight that under red-light irradiation, the bacteriochlorin catalyst has achieved 89% monomer conversion in just 12 hours, with

Synthesis and characterizations of highly luminescent 5-isopropoxybenzo[rst]pentaphene

• Islam S. Marae,
• Jingyun Tan,
• Rengo Yoshioka,
• Zakaria Ziadi,
• Eugene Khaskin,
• Serhii Vasylevskyi,
• Ryota Kabe,
• Xiushang Xu and
• Akimitsu Narita

Beilstein J. Org. Chem. 2025, 21, 270–276, doi:10.3762/bjoc.21.19

• and photonics [32][33][34][35]. However, precise preparation and shape control over organic crystals are still elusive targets [36]. We carried out SEM analysis of crystals of BPP-OiPr 3 obtained by slow evaporation of its solution in a mixture of dichloromethane and n-hexane (Figure 3). The formation

Three-component reactions of conjugated dienes, CH acids and formaldehyde under diffusion mixing conditions

• Dmitry E. Shybanov,
• Maxim E. Kukushkin,
• Eugene V. Babaev,
• Nikolai V. Zyk and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 262–269, doi:10.3762/bjoc.21.18

• days (TLC or NMR control). After completion of the reaction, the solvent was removed under reduced pressure, and the residue was purified by column chromatography on silica gel using chloroform as eluent. ((1S,4S)-Bicyclo[2.2.1]hept-5-ene-2,2-diyl)bis(phenylmethanone) (8) and phenyl((4aR,7aS)-2-phenyl

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

• be isolated in 82% yield. Several control experiments were performed to investigate the possible mechanism of the reaction (Scheme 5). In Table 1, entry 17, no disulfide product was formed at 80 °C, however, an 85% yield of thiosulfonate was observed. This indicated that thiosulfonate could be an

• ]. Control experiments were performed for the 3-thioflavone formation process. It was found that without the addition of sodium p-toluenesulfinate, 3a was converted to 4H-chromen-4-one (3aa) in high yield (reaction 3 in Scheme 5). When 3aa and 1a were used as substrates, product 4a could be obtained in high

• ) exhibited a lesser effect. Considering that TEMPO, as an oxidizing agent, affected the reaction, it could be concluded that the reaction did not proceed through a free radical mechanism. Based on the results of the control experiments and the related literature [26][30][41][52], a possible mechanism for the

Effect of substitution position of aryl groups on the thermal back reactivity of aza-diarylethene photoswitches and prediction by density functional theory

• Misato Suganuma,
• Daichi Kitagawa,
• Shota Hamatani and
• Seiya Kobatake

Beilstein J. Org. Chem. 2025, 21, 242–252, doi:10.3762/bjoc.21.16

• which the photogenerated isomers are thermally unstable at room temperature and return to the initial isomers not only by photoreaction but also by the thermal back reaction, are utilized for eyeglass lenses [43], security inks [44], and real-time holograms [45]. Especially, it is important to control

• and predict the thermal reactivity of T-type molecules, and many researchers have made their efforts to control the thermal reactivity in various molecular systems by performing chemical modifications on the molecular structures [46][47][48]. For instance, Aprahamian and co-workers reported that

• solution samples were not degassed. The temperature control for UV–vis absorption spectral measurements was carried out using a UNISOKU CoolSpek UV/CD or an Ocean Optics CUV-QPOD. Material Synthesis of compounds N4 and I1–I4 The synthesis of the compounds is shown in Scheme 2. 4-Methyl-5

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• , entries 10–13), and conducting the reaction under air instead of nitrogen significantly lowered the yield (Table 1, entry 14). Control experiments showed that the absence of PIDA resulted in no reaction (Table 1, entry 15), while the use of a 40 W light source or the absence of visible light also reduced

• demonstrates the versatility of our methodology and its potential for further exploration in diverse chemical spaces. To gain a deeper understanding of the mechanism behind the observed reaction, we conducted a series of control experiments as outlined in Scheme 3a. Initially, we performed the model reaction

• . Reaction conditions: 1 (0.2 mmol), 2 (1.4 mmol), and PIDA (0.8 mmol) in solvent (2 mL) irradiated with 72 W white LEDs at room temperature for 12 h under a N2 atmosphere. Yields refer to isolated yield. aα,α-Difluorobenzeneacetic acid (2 equiv) was used. Control experiments and plausible mechanism

Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization

• Asahi Kanno,
• Ryo Tanifuji,
• Satoshi Yoshida,
• Sota Sato,
• Saori Maki-Yonekura,
• Kiyofumi Takaba,
• Jungmin Kang,
• Kensuke Tono,
• Koji Yonekura and
• Hiroki Oguri

Beilstein J. Org. Chem. 2025, 21, 226–233, doi:10.3762/bjoc.21.14

• -fluorobenzene (see Scheme 2 and Supporting Information File 1 for details). Copper(I)-catalyzed three-component coupling reaction of alkyne 8, THIQ 9, and benzaldehyde, proceeded with exquisite control of regioselectivity to afford 10 in an excellent yield of 92% [43][44][45][46]. This efficient cascade

• and a catalytic amount of triethylamine were used in dichloromethane with careful control of the reaction temperature at 15 °C (Table S2, Supporting Information File 1). With the 2,3-diaminobenzofuran 11 in hand as the designed cyclization precursor, we explored the construction of the left

• activation of the alkyne triple bond and allows precise control of the chemo- and regioselectivities for the assembly of the left isoquinoline substructure. The unexpected discovery of the fluorescent intermediate 18 adds an intriguing dimension to our current synthetic investigation and suggests potential

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• substrate scope of boronic acids was limited in this transformation. To elucidate the reaction process, kinetic and control experiments were conducted, which led to the proposed reaction pathway for the copper-mediated synthesis of N-arylamides from dioxazolones as shown in Figure 4. Initially, copper(I

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

• esters containing a quaternary stereocenter, and the control of regioselectivity depended on the bulkiness of the substrates. Additionally, the electrochemical system served as an internal syringe pump, generating quinone from hydroquinone in situ through anodic oxidation, which enhanced the

• transformations remains challenging due to the difficulty in controlling the stereo- and chemoselectivity of highly reactive radical intermediates. Future efforts should focus on designing new ligand frameworks to broaden substrate scopes and enhance selectivity control. The use of greener solvents is also

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• additive. Some control experiments support a mechanism whose key intermediates are the formation of the iminium ion XIX, originated from aniline with formaldehyde which serves as the C1 building block, and the generation of the cyclic α,β-unsaturated ethers XX by Cu(OTf)2-catalyzed dehydrogenation of the

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

• , previous findings from the literature, and experimental results, a reaction mechanism was proposed [46]. Hydrogen bonding as well as π–π interaction with the catalyst (R)-C22 activates both substrates in the stable intermediate Int-35. This stabilized state ensures the concerted control of

• (Scheme 23) [47]. These reactions were catalyzed by both BINOL-derived (TRIP) CPA (S)-C23 and SPINOL-derived CPA (S)-C24, providing axially chiral products 71 and 73, respectively. Control experiments showed the importance of the N–H group on the indole ring and the presence of both carboxylate groups in

• azodicarboxylate catalyzed by CPA (R)-C23 provided axially chiral unprotected biaryls (S)-74a–r and axially chiral protected biaryls (R)-75a–r (Scheme 24) [48]. Consistently high enantioselectivities and yields were reported with various binaphthyl and biphenyl substrates. Control experiments revealed the

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• stomatocyte configuration. Several critical factors contribute to this transformation. Firstly, the application of osmotic pressure which must be sufficiently robust. This control is notably easier with the addition of PEG, as it swiftly creates a substantial osmotic gradient [19]. Secondly, the vesicle's

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

• commercial and in-house developed equipment. Normally, HTE for organic chemistry will include a liquid transfer module, a reactor stage, and analytical tools for product characterization. When the full experimental process is automated and coupled with a centralized control system performing ML optimization

• to increase the experimental throughput. Commonly, batch platforms include a liquid handling system for setting up reactions based on a plunger pump (e.g., syringe, pipette), a reactor capable of heating and mixing, and in-line/online analytical tools. HTE in batch excels in the control of

• of stereoselective Suzuki–Miyaura couplings, offering precise control over both categorical and continuous variables (Figure 2a) [15]. The integrated robotic system containing a four-needle dispense head facilitated the delivery of reagents in low volume and slurries, ensuring the accuracy and

Chemical glycobiology

• Elisa Fadda,
• Rachel Hevey,
• Benjamin Schumann and
• Ulrika Westerlind

Beilstein J. Org. Chem. 2025, 21, 8–9, doi:10.3762/bjoc.21.2

• methods that underlie modern glycobioinformatics approaches [15]. Validation of glycoprotein structure is an important aspect of contemporary structural biology, and Dialpuri et al. present the Privateer database to allow for facile quality control of such structures [16]. Finally, Barillot et al. bridge

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• scavengers capable of abstracting the radical species that could emerge in the reaction media. The use of galvinoxyl proved to be insufficient to conclude since a control experiment showed that HIRs 2 decompose in the presence of galvinoxyl. When using TEMPO (Scheme 5), sulfinamide 6aa was not detected, but

• recognized ionic character of the sulfenate ion generated in the retro-Michael addition, on the results obtained with TEMPO (Scheme 5), and also on the results obtained when the reaction was carried out in the absence and presence of light, as well as the control experiments in the absence of BBX (see

Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• -protected Michael acceptor, derived from proline, allowed for preparation of compound 27 with a 35% yield in 4 hours without control of diastereoselectivity (dr = 1:1). Finally, to prove that the optimized reaction also works at a larger scale, the model reaction was carried out on a 2.2 mmol scale (Figure

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• derivatives 3 in yields up to 99%, up to 20:1 dr, and up to 99% ee [24]. This work represents the first enantioselective bifunctional catalytic inverse electron demand Diels–Alder reaction that occurs with a dual control of the dienophile HOMO and diene LUMO energies of the substrates. The amino group of the

• calculations also revealed that due to kinetic control the activation of the C2 carbon of the dienolate is preferred vs the C4 atom, therefore only one regioisomer is observed. Additionally, the asymmetric IEDADA reaction could be performed at a higher scale (1 mmol) leading to the synthesis of the

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

• OD600 and resazurin (RSZ) metabolic assay, respectively. The final concentration of DMSO in the assays was 1% (v/v). The negative controls consisted of inoculum and 1% DMSO. The antibiotic tobramycin (Sigma-Aldrich; 16 µg/mL) was used as a positive control. The initial OD600 and final OD600 were read

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• stabilizes their secondary structure and their metabolic stability, which is useful for numerous applications [3][4][5]. Indeed, the cyclic structure considerably reduces the number of possible rotational conformers, allowing a rational control of the 3D conformational space. Among these cyclic structures

• strategy, the control of the stereoselectivity of the intramolecular aza-Michael addition could be envisaged with various chiral catalysts in further studies. These heterocyclic hydrazino acids, when incorporated into the peptidic structure, appear to confer an extended conformation. These interesting

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• conducted at a concentration of 10 μM, with donepezil serving as a positive control. To measure their impact on cellular tau oligomerization, the fluorescence resonance energy transfer (FRET) signal intensity was quantified in a cellular tau FRET assay at the same 10 μM concentration, using MK-886, a known

• tau-oligomerization inhibitor, as the positive control. Two compounds (7a and 7b, Figure 7) demonstrated a high inhibitory activity against AChE and tau-oligomerization, which were selected for further exploration. The neuroprotective effects of the compounds were assessed in comparison to MK-886 and

• deacetylase substrate MAL to determine the inhibitory activity, and using sirtinol as positive control. When compared to sirtinol (IC50 = 67 µM), selected compounds showed moderate affinity towards SIRT2, with IC50 values ranging from 118 to 126 µM (Figure 10). Gewald reaction: Cannabinoid receptors have been

Controlled oligomerization of [1.1.1]propellane through radical polarity matching: selective synthesis of SF₅- and CF₃SF₄-containing [2]staffanes

• Jón Atiba Buldt,
• Wang-Yeuk Kong,
• Yannick Kraemer,
• Masiel M. Belsuzarri,
• Ansh Hiten Patel,
• James C. Fettinger,
• Dean J. Tantillo and
• Cody Ross Pitts

Beilstein J. Org. Chem. 2024, 20, 3134–3143, doi:10.3762/bjoc.20.259

• oligomerizations involving [1.1.1]propellane – i.e., to make [n]staffanes – has been notoriously challenging to control when n > 1 is desired. Herein, we report selective syntheses of SF5- and CF3SF4-containing [2]staffanes from SF5Cl and CF3SF4Cl, demonstrating cases whereby oligomerization is preferentially

• is conceptually appealing, radical additions of X–Y across 1 in practice can be challenging to control and often lead to complex mixtures of functionalized [n]staffanes, n = 1–5 (Figure 1, top) [2][31][32][33][34]. Even though [n]staffanes are often separable by column chromatography, the yields for