Silica gel with covalently attached bambusuril macrocycle for dicyanoaurate sorption from water

• Michaela Šusterová and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2025, 21, 2604–2611, doi:10.3762/bjoc.21.201

• ]. In the field of anion extraction, there is growing interest in solid-phase substrates functionalized with synthetic macrocyclic receptors. These materials employ a supramolecular approach based on specific host–guest interactions between the immobilized macrocycle and the guest in solution, often

• [10]. Although synthetic anion receptors have attracted increasing attention in the field of supramolecular chemistry, there are still relatively few reports of materials that employ macrocyclic receptors to recognize and selectively bind anionic species specifically in aqueous environments. For

• -sized” molecular box has been used to extract various anions from water [12]. Another family of macrocyclic compounds suitable for anion recognition and binding are bambusurils (BUs). BUs act as very potent anion receptors in both organic solvents and water. Furthermore, their portals can be variously

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• ) exhibits high specificity and regulatory effects on ryanodine receptors (RyRs) [19][20]. It is among the few small organic molecules identified to date that can modulate these receptors. Dysfunctions of RyRs are closely associated with various diseases: mutations in RyRs can cause genetic disorders such as

• core, successfully completing the first asymmetric total synthesis of ryanodol (4) in 41 steps. To elucidate the role of the C15 hemiacetal hydroxy group in ryanodine (1)-type diterpenoid natural products in binding to ryanodine receptors, the authors initially proposed reducing the lactone moiety in

• intramolecular oxa-bridged ring, culminating in the first total synthesis of 3-epi-ryanodol (5) and 3-epi-ryanodine (30). The subsequent biological evaluation revealed that 30 possesses only 1% of the affinity of ryanodine (1) for ryanodine receptors (RyRs). Inoue’s total synthesis of ryanodine, ryanodol, 3-epi

Synthesis and characterization of a isothiouronium-calix[4]arene derivative: self-assembly and anticancer activity

• Giuseppe Granata,
• Loredana Ferreri,
• Claudia Giovanna Leotta,
• Giovanni Mario Pitari and
• Grazia Maria Letizia Consoli

Beilstein J. Org. Chem. 2025, 21, 2535–2541, doi:10.3762/bjoc.21.195

• class of interest in the search for new chemotherapeutic agents. They are known inhibitors of protein kinase C [40] and agonists of the GABA-type [41] and histamine-H3 receptors [42]. S-Allylic isothiouronium salts substituted with aliphatic groups have shown to combine high antitumor activity against

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• of cyclopentane derivatives, promising for the synthesis of iridoids and compounds, that stimulate the formation of receptors that prevent platelet aggregation [75]. The derivatives of the Diels–Alder adduct of LG and piperylene, keto epoxide 146 and its analogue 152 lacking the spiro-fused

Conformational effects on iodide binding: a comparative study of flexible and rigid carbazole macrocyclic analogs

• Guang-Wei Zhang,
• Yong Zhang,
• Le Shi,
• Chuang Gao,
• Hong-Yu Li and
• Lei Xue

Beilstein J. Org. Chem. 2025, 21, 2369–2375, doi:10.3762/bjoc.21.181

• fluorescence quenching efficiency upon iodide binding compared to the rigid WDG (KPBG/KWDG = 22.78), demonstrating its potential as a highly sensitive optical probe and offering a novel strategy for engineering dynamic supramolecular receptors. Two carbazole-based macrocyclic probes, PBG (flexible benzene ring

• interplay between conformational dynamics and localized structural adaptations governing anion recognition. The findings advance the rational design of tunable, high-affinity anion receptors and deepen the understanding of conformational regulation in supramolecular systems. Keywords: anion recognition

• . This experiment supports a 1:1 stoichiometric binding between the guest TBAI and the host PBG in CDCl3. Then, the binding affinity of the two receptors to iodine ions was further studied, and the changes of UV–visible absorption and fluorescence spectra of the two receptors to anions in CHCl3 were

Insoluble methylene-bridged glycoluril dimers as sequestrants for dyes

• Suvenika Perera,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 2302–2314, doi:10.3762/bjoc.21.176

• -type receptors (e.g., H2) and studied their use as sequestrants for organic micropollutants [39]. In this paper, we extend this line of inquiry toward the use of the water-insoluble glycoluril dimer-derived acyclic CB[n] as sequestrants for dyes. Results and Discussion This Results and Discussion

• discern the effect of smaller aromatic sidewalls. The synthesis of acyclic CB[n]-type receptors follows a building block approach involving the reaction of a glycoluril bis(cyclic) ether with an activated aromatic wall by a double electrophilic aromatic substitution process [30]. Scheme 2 shows the

• insoluble in water as required for their use as solid state sequestrants. Unlike most acyclic CB[n]-type receptors, G2W1–G2W4 are soluble in organic solvents (G2W1 and G2W2: soluble in CHCl3, CH2Cl2, DMSO, and TFA but insoluble in methanol, acetone, acetonitrile, and hexane; G2W3: soluble in DMSO and TFA

Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• risk, as the strongly bound compounds affect membrane integrity, thus influencing the conformation of receptors and possibly causing side effects. As the outcome of pharmacokinetic characterization, lead-likeness was interpreted in Table 2 and Table 3, considering kinetic solubility, GI PAMPA

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• the protein-binding site than the bent Z-isomer. However, it would be more desirable to have an inactive molecule in its most stable state which can be activated by irradiation [51][59]. Hernando and co-workers were able to design photoswitchable neurotransmitters of ionotropic kainate receptors by

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• [52]. The key design features are: 1) The mannose groups at the upper rim confer specific recognition ability for cancer cell surface receptors; 2) The hydrophobic core formed by the alkyl chains at the lower rim and the hydrogen-bonding network constructed by the thiourea unit can efficiently

• and azo linkages deepened the cavity and enhanced the interaction strength with drugs. The biotin on the upper rim endows biotin-SAC4A with the ability to actively target tumor cells based on the interaction between biotin and biotin receptors, thereby improving antitumor efficacy. DOX@biotin-SAC4A

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• , the chemical synthesis of thiotrehalose analogs [116][117] provides a versatile tool for the construction of therapeutically relevant ligands or inhibitors of carbohydrate-specific innate immune receptors. Synthetic thiodigalactosides and their derivatives have been identified as selective inhibitors

Formal synthesis of a selective estrogen receptor modulator with tetrahydrofluorenone structure using [3 + 2 + 1] cycloaddition of yne-vinylcyclopropanes and CO

• Jing Zhang,
• Guanyu Zhang,
• Hongxi Bai and
• Zhi-Xiang Yu

Beilstein J. Org. Chem. 2025, 21, 1639–1644, doi:10.3762/bjoc.21.127

• the 6/5/5 skeleton, and a Heck coupling reaction constructing the [3.2.1] framework, are the two key reactions in this 11-step synthesis. Keywords: [3 + 2 + 1] cycloaddition; selective estrogen receptor modulators; synthesis; tetrahydrofluorenone; Introduction Estrogen receptors (ERs) [1][2] are

• widely distributed nuclear receptor proteins and include two subtypes, ERα [3][4] and ERβ [5][6]. These receptors can bind 17β-estradiol with similar affinity, facilitating the transfer of estrogen to various tissues in the body. Due to this, 17β-estradiol as non-selective ligand has been extensively

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• important role as building blocks for peptide synthesis [1][2][3][4][5], as organocatalysts [6][7][8][9][10] and as enzyme inhibitors [4][11][12][13]. The incorporation of such amino acids into peptides can, for example, influence peptide conformation, the binding affinity to receptors [14], as well as

Dicarboxylate recognition based on ultracycle hosts through cooperative hydrogen bonding and anion–π interactions

• Wen-Hui Mi,
• Teng-Yu Huang,
• Xu-Dong Wang,
• Yu-Fei Ao,
• Qi-Qiang Wang and
• De-Xian Wang

Beilstein J. Org. Chem. 2025, 21, 884–889, doi:10.3762/bjoc.21.72

• cellular metabolism; they regulate the activity of numerous enzyme receptors, and serve as intermediates in the synthesis of more complex biomolecules [21]. However, excessive consumption or production, as well as insufficient clearance of dicarboxylates, can lead to various health problems [22

• importance. Despite the development of a number of receptors for dicarboxylates [21][26][27], their recognition remains a challenging task due to their strong hydrophilicity (−400 kJ/mol) [28][29], dispersed negative charges at both ends, complex shapes, and flexible conformations. Moreover, the similar

Unraveling cooperative interactions between complexed ions in dual-host strategy for cesium salt separation

• Zhihua Liu,
• Ya-Zhi Chen,
• Ji Wang,
• Qingling Nie,
• Wei Zhao and
• Biao Wu

Beilstein J. Org. Chem. 2025, 21, 845–853, doi:10.3762/bjoc.21.68

• separation [4][5][6][7][8]. Building on the extensive research into anion and cation receptors within the realm of supramolecular chemistry [9][10][11][12], numerous heteroditopic ion-pair receptors have been elaborately developed [13][14][15]. These receptors, consisting of binding sites for both anions and

• cations within a single molecule, have facilitated advancements in ion-pair recognition. This progress has led to the development of ion separation utilizing ion-pair receptors [16][17][18][19][20], which eliminate the need for auxiliary reagents to balance overall charges compared to the use of

• individual anion or cation receptors [21]. An alternative approach for ion separation involves the combination of an anion receptor and a cation receptor, known as the dual-host strategy [22][23][24]. Unlike ion-pair receptors, this strategy avoids the intricate, multi-step synthesis required for designing

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

• are acyclic CB[n]-type receptors which have been extensively studied by our lab and others over the past decade [42][43][44][45][46][47][48][49][50][51][52]. Figure 1 shows the chemical structure of the prototypical acyclic CB[n]-type known as M1 [53][54]. M1 features a central glycoluril tetramer

• modular synthesis, acyclic CB[n] can be easily modified synthetically [42][43][44][45][46][47][61]. Acyclic CB[n]-type receptors featuring different length glycoluril oligomers (monomer–pentamer) and different aromatic walls (e.g., naphthalene, anthracene, triptycene) have been studied [42][62][63][64][65

• chemical shift (Δδ) for C1·guest. As the central hydrophobic binding domain of the guests we selected alkylene, p-xylylene, cyclohexane, and adamantane moieties that are known to bind well to (acyclic) CB[n] receptors [71][72][73]. The cross-sectional area of this hydrophobic moiety increases as follows

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

• (III, Figure 11) [149]. These effects have been exploited to control the conformations of simple bioactive amines such as γ-aminobutyric acid (GABA, 86, Figure 11) [150][151][152][153][154][155]. GABA is a neurotransmitter that binds to a variety of different GABA receptors, and information about the

• target-binding conformations of GABA at these various receptors can be gleaned by investigating fluorinated GABA analogues (e.g., 87–90). For example, the enantiomeric analogues 87 and 88 have similar activity at the GABAA receptor, and this suggests that the binding conformation of GABA has an extended

• that it is not selective towards injured tissue: it also binds to μ-opioid receptors in healthy tissue, causing side-effects. To overcome this drawback, a fluorinated analogue of fentanyl ((±)-105) was developed [177]. The electron-withdrawing fluorine substituent of 105 lowers the pKaH of the

Binding of tryptophan and tryptophan-containing peptides in water by a glucose naphtho crown ether

• Gianpaolo Gallo and
• Bartosz Lewandowski

Beilstein J. Org. Chem. 2025, 21, 541–546, doi:10.3762/bjoc.21.42

• receptors; molecular recognition; monosaccharides; tryptophan; Introduction Tryptophan plays a crucial role in a variety of biological processes [1][2]. For example, it is critical for electron transfer in proteins [3] and is a key component of several membrane proteins as well as short antimicrobial

• peptides [4][5]. Tryptophan also serves as a substrate to produce hormones such as serotonin or melatonin [6][7]. Due to the biological relevance of tryptophan synthetic receptors for this amino acid are highly sought after [8]. From a biological perspective it is especially desirable to achieve selective

• binding of tryptophan in water [9]. However, the development of selective amino acid receptors in aqueous environments is challenging since it requires a combination of hydrophobic and polar interactions for binding [10][11][12]. As a result, the number of reported selective receptors for tryptophan in

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

• methods in materials discovery are unlikely to discover solution-phase sensors or catalysts without a rational starting point to build from. Instead, new receptors [413] and catalysts [414][415][416] will likely arise from improvements in computational rationalization of experimental data [415][417

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

• in the glycosciences. A key aspect is the modelling of protein–glycan interactions. Marcisz et al. study the power of umbrella sampling in distinguishing the interactions between different glycosaminoglycans and their receptors [14]. Nieto-Fabregat et al. provide a detailed overview on computational

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

• to various enzymatic systems or receptors implicated in AD pathology. In 2019, Malek et al. [43] designed and obtained a new family of 1,4-dihydropyridines (DHPs), as a series of MTDLs, which were prepared using a multicomponent reaction, particularly the Hantzsch reaction (Scheme 9). The synthesized

• 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

• heterocyclic core. The novel compounds were first evaluated using β-arrestin recruitment assays in CHO (chinese hamster ovary) cells overexpressing human GPR55. These new compounds have been evaluated in competitive binding assays for cannabinoid receptors, but all of them showed to be selective for GPR55 (>4

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

• , porphyrins and corroles, which are structurally related to porphyrins. Calix[4]pyrroles are versatile receptors in supramolecular chemistry while porphyrins are considered as ‘pigment of life’ due to their role in vital biological processes. Beyond their natural functions, synthetic porphyrins have been

Tailored charge-neutral self-assembled L₂Zn₂ container for taming oxalate

• David Ocklenburg and
• David Van Craen

Beilstein J. Org. Chem. 2024, 20, 3007–3015, doi:10.3762/bjoc.20.250

• development of effective receptors for their detection. In particular, the smallest dicarboxylate, oxalate, presents a significant importance due to its widespread presence in nature and its association with various diseases. Yet, very little attention was devoted to the recognition of oxalate with metal

• -driven self-assemblies like cages or containers while numerous classic organic receptors for oxalate exist. This discrepancy is astonishing because metallocontainers or metallocages have advantages over classic macrocycles or organocages like a higher modularity and good preorganization paired with a

• ; metallocontainer; oxalate; Introduction Dicarboxylic acids and their corresponding anions are essential intermediates in the biosynthesis of proteins and important biological metabolites [1][2]. As a result, the development of receptors for this class of compounds is of high interest [3][4][5]. Oxalate, the

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• represent promising candidates for drug discovery, because of their improved water solubility, membrane permeability, and improved recognition by the respective receptors [16]. The present article aims to provide an updated review of the chemistry and biological applications of N-glycosides of indigo

• TRAIL and CD95 agonists [47]. A detailed investigation of apoptotic signaling pathways revealed that TRAIL resulted, based on a negative feed-back loop, in a rapid downregulation of both agonistic TRAIL receptors DR4 and DR5. However, the presence of compound E-β-46b resulted in a compensation of this

• negative feed-back loop by TRAIL and an upregulation of both receptors. In addition, a loss of mitochondrial membrane potential and release of cytochrome c was observed which gave rise to an activation of intrinsic apoptosis pathways. The mitochondrial response seems to be related to an upregulation of Bax

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

• literature. In light of the promise of appropriately designed nonplanar porphyrins as receptors and catalysts we report here on our efforts to use the Suzuki–Miyaura reaction for the modification of the o,m,p-phenyl positions in 5,10,15,20-tetraryl-2,3,7,8,12,13,17,18-octaethylporphyrins. Results and

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• chemistry highlights derivatives capable of interacting with multiple receptors or enzymes, making them ideal candidates for drug discovery. Dihydropyrimidinones (DHPMs) and their derivatives are particularly noteworthy within this category. Accordingly, their synthesis is of significant interest for