Molecular tweezer–peptide conjugates disrupt the protein–protein interaction between survivin and histone H3 essential in mitosis

• Catherine Gsell,
• Philipp Rebmann,
• Karina Opara,
• Christine Beuck,
• Peter Bayer,
• David Bier,
• Ingrid R. Vetter and
• Thomas Schrader

Beilstein J. Org. Chem. 2026, 22, 557–567, doi:10.3762/bjoc.22.41

• Ca2+ cation from the crystallization buffer, is visible next to the cavity (Figure S12 in Supporting Information File 1). From recent complexation experiments with lipids, it is known that even uncharged alkyl groups may occupy the tweezer cavity and gain binding energy through dispersive interactions

• and the hydrophobic effect [16]. Ca2+ may also interact with the high π-electron density inside the cavity, although in direct titrations, only small affinities in the millimolar range have been determined for this cation [17]. This observation not only indicates a competition of the (putative

• conjugates for well-accessible lysines in the CPC. For efficient docking of a tweezer molecule onto a lysine residue on the protein surface, only one phosphate moiety is sufficient, which locks the included lysine cation into an ion pair [20]. In MD simulations between survivin and the truncated version of

Synthesis and uranyl(VI) extraction performance of a calix[4]pyrrole–tetrahydroxamic acid receptor

• Sara Karnib,
• Rana Baydoun,
• Wissam Zaidan,
• Nancy AlHaddad,
• Omar El Samad,
• Bilal Nsouli,
• Francine Cazier-Dennin and
• Pierre-Edouard Danjou

Beilstein J. Org. Chem. 2026, 22, 486–494, doi:10.3762/bjoc.22.36

• receptors bearing both anion- and cation-binding sites, as well as systems capable of promoting ion-pair formation [23][24]. As effective chelating agents for a broad range of transition metals, hydroxamic acids constitute an important class of organic compounds that have attracted considerable attention

• deprotonation. The coordination of the hydroxamic acid groups to the uranyl cation stabilizes the deprotonated hydroxamate form, effectively lowering the apparent pKa and enabling strong binding even at low pH [33]. It is important to mention that the formation of the stable 5-membered chelate between the

Synthesis and anti-cancer activity of naphthalimide–organylselanyl conjugates

• Rajkumar Ravi and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2026, 22, 416–435, doi:10.3762/bjoc.22.29

• . However, as shown in Supporting Information File 1, Figure S19, a representative fragment ion with a m/z value of 318.0028 could be matched with naphthalimide selenenium cation, having a calculated m/z value of 318.0028. Single-crystal X-ray diffraction analysis of compound 7 A single crystal of compound

Cone p-aminocalix[4]arenes enriched with ‘clickable’ alkyne or azide functionalities

• Ilia Korniltsev,
• Vasily Bazhenov,
• Alexander Gorbunov,
• Dmitry Cheshkov,
• Stanislav Bezzubov,
• Vladimir Kovalev and
• Ivan Vatsouro

Beilstein J. Org. Chem. 2026, 22, 399–415, doi:10.3762/bjoc.22.28

• or a trialkylammonium cation inside the joint cavity formed by two cone calix[4]arene macrocycles [46][47][48][49][50][51][52][53][54]. This phenomenon has been thoroughly investigated, including the effects from substituents in the urea groups and/or at the calixarene narrow rim upon the

Electrosynthetic access to unsymmetrical oxaza[8]helicenes with high chiral stability and strong circularly polarized luminescence (CPL)

• Tin Zar Aye,
• Rubal Sharma,
• Muthu Karuppasamy,
• Daiya Suzuki,
• Haruka Nakajima,
• Yoshitane Imai,
• Mitsuhiro Arisawa,
• Mohamed S. H. Salem and
• Shinobu Takizawa

Beilstein J. Org. Chem. 2026, 22, 372–382, doi:10.3762/bjoc.22.25

• products were detected under the optimized conditions (Scheme 2). Based on our previous reports [48][56], DFT calculations, and cyclic voltammetry (CV) analyses (Figure 1), anodic single-electron transfer (SET) is expected to occur first from 3, generating the electrophilic radical cation [3]·+ as 3 (Eox

• = 0.735 V vs Fc/Fc+ in CH2Cl2) is oxidized more readily than the 2-naphthol partners (Eox of 4a = 1.081 V and Eox of 4b = 1.286 V vs Fc/Fc+ in CH2Cl2). The radical cation [3]·+ then undergoes rapid deprotonation to form a neutral radical intermediate (Int-I) with high spin density at the reactive site

• the pKa of [3]·+ radical cation and spin density of neutral radical intermediate Int-I (optimized at the UB3LYP/6-31G+(d,p) level of theory with IEPCM model as solvation of DCM. Grimme’s dispersion with the original D3 damping function was applied as empirical dispersion correction to the optimized

Recent advances in the cleavage of non-activated amides

• Eun-Sol Choi and
• Hyo-Jun Lee

Beilstein J. Org. Chem. 2026, 22, 352–369, doi:10.3762/bjoc.22.23

• catalysis, electrophilic activation, strong base-counter-cation systems, and N-based activating groups that enable chemoselective bond cleavage. Together, these developments provide powerful tools for amide functionalization and offer new opportunities for efficient, practical, and selective syntheses

• -promoted transformations enhanced by alkali-metal counter-cation effects, and (iii) installation of activating groups on the nitrogen to enable chemoselective cleavage under tailored conditions. These approaches collectively offer promising avenues for the efficient transformation of non-activated amides

• electrophilic benzylating reagent (Scheme 7) [55]. DPT-BM functions as an O-benzylating reagent that generates benzyl cation equivalents upon dissolution in the solvent under non-acidic conditions. Thus, the reaction of an amide with DPT-BM is proposed to form a benzyl imidate salt J, which subsequently

Ring contraction and ring expansion reactions in terpenoid biosynthesis and their application to total synthesis

• Nicolas Kratena,
• Nicolas Heinzig and
• Peter Gärtner

Beilstein J. Org. Chem. 2026, 22, 289–343, doi:10.3762/bjoc.22.21

• synthesis, are gathered. Our definition includes both radical and polar ring-size altering reactions, transannular cyclisations of macrocycles and cation-mediated rearrangements where fitting. Goal of this review is to gather and compare mechanistic proposals for the biogenesis of ring-size-altered

• of the bicyclo[3.1.0]hexane system present in thujane monoterpenes [56] (see Scheme 2A). Starting from geranyl pyrophosphate (6), monoterpene cyclases first build up a 6-membered ring with an exocyclic carbocation, commonly referred to as α-terpinyl cation 6a. From there, a 1,2-hydride shift gives

• rise to the isomeric terpin-4-yl cation 6b. By way of cyclopropane formation, a different, so called, thujyl cation 6c is conceivable. Elimination then furnishes the ring-contracted 5/3-ring systems from the original cyclohexyl intermediate to give sabinene (7) and α-thujene (8). Another example of a 6

Synthesis of diaryl phosphates using phytic acid as a phosphorus source

• Kazuya Asao,
• Seika Matsumoto,
• Haruka Mori,
• Riku Yoshimura,
• Takeshi Sasaki,
• Naoya Hirata,
• Yasuyuki Hayakawa and
• Shin-ichi Kawaguchi

Beilstein J. Org. Chem. 2026, 22, 213–223, doi:10.3762/bjoc.22.15

• recovery of 4.2% based on the total P analysis data. Considering the losses that occurred during the purification steps, these results were consistent with the fact that 100 g of rice bran contained approximately 6 g of phytic acid [1][2][3]. Subsequently, the isolated phytate was desalted using a cation

• -exchange resin to obtain phytic acid. Cation exchange was performed via a shaking method rather than a column method owing to the low solubility of phytate in water. The 31P NMR spectrum of the obtained phytic acid clearly shows four peaks corresponding to the non-equivalent phosphorus atoms in the phytic

• ). The residue was washed with methanol and dried under vacuum overnight. Finally, 2.52 g of the crude sodium phytate was obtained as a white solid. Purification of extracted phytic acid Well-conditioned DOWEX 50W × 2 100–200 mesh (H) cation exchange resin (Dow Chemical Co., Midland, MI, USA) (60 mL) was

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• , Scheme 24) towards further protonation – often proceeding via more stabilized tertiary carbocation intermediates (for example: 153 is more stable compared to initially formed alkenyl cation 152, Scheme 24) [91]. This protonation pathway commonly leads to the formation of gem-dichloride species 151, which

• ). Importantly, a lower alkyne-to-chloride ratio resulted in diminished yields of 155. The authors proposed that the key intermediate is a linear vinyl cation with a planar geometry (217, Scheme 40B), wherein the empty p-orbital lies in the molecular plane. As such, nucleophilic attack occurs within this plane

• acidity [145]. This transformation remained unexplored for nearly a decade until Kabalka demonstrated that the benzylic cation could be accessed directly from the corresponding alcohol via its conversion to the benzyloxyboron dichloride (Scheme 42) [146]. Subsequently, Kabalka reported an improved variant

Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• -rich and electron-poor substituents. This reaction was carried out between arylcyclopropanes 5 and acyl fluoride 4 in the presence of NHC (10 mol %) and 4CzIPN (5 mol %). Mechanistic studies showed that the cascade proceeds via nucleophilic ring-opening of a cyclopropyl radical cation D with subsequent

• substrate 7, generating the aryl radical cation C along with the formation of corresponding radical anion of the photocatalyst (PC•–). The reduction potentials are (E1/2(P/P•–) = –1.37V vs SCE for [Ir(dF(CF₃)ppy)₂(dtbbpy)]PF₆ and –1.21V vs SCE for 4CzIPN as an organophotocatalyst. This method permits the C

• was described. Aromatic C(sp2)–H bond acylation was achieved by dual catalysis through cooperative NHC and organophotoredox-catalyzed C–C cross-coupling of a benzo-fused aryl radical cation C with stable ketyl radical B as the key step. LED irradiation of photocatalyst leads to photoexcited PC*, which

Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• cation were consistent with earlier reports [2][26], though the configurations of the intermediates were clearly delineated. The authors proposed that dicarbonyl compound 50 serves as the key intermediate diverging to all Illicium sesquiterpenes, with a retro-Dieckmann condensation and aldol reaction

Ni-promoted reductive cyclization cascade enables a total synthesis of (+)-aglacin B

• Si-Chen Yao,
• Jing-Si Cao,
• Jian Xiao,
• Ya-Wen Wang and
• Yu Peng

Beilstein J. Org. Chem. 2025, 21, 2548–2552, doi:10.3762/bjoc.21.197

• (2) and C (3), featuring a visible light-catalyzed radical cation cascade for the formation of the C8–C8′ and C2–C7′ bonds [6]. Subsequently, they improved the reaction conditions to achieve the racemic synthesis of aglacins A (1) and E (4) as well [7]. In 2021, the Gao group described the total

Synthesis of the tetracyclic skeleton of Aspidosperma alkaloids via PET-initiated cationic radical-derived interrupted [2 + 2]/retro-Mannich reaction

• Ru-Dong Liu,
• Jian-Yu Long,
• Zhi-Lin Song,
• Zhen Yang and
• Zhong-Chao Zhang

Beilstein J. Org. Chem. 2025, 21, 2470–2478, doi:10.3762/bjoc.21.189

• current interest in the synthesis of complex natural products via photochemical reactions, we decided to achieve such an unusual bond cleavage (Figure 1a, path A) of cyclobutenone by generating a radical cation species via a PET reaction. The synthetic plan is shown in Figure 1c and includes a PET

• -initiated [2 + 2] cyclization of the tryptamine-substituted cyclobutenone K to form the radical cation L, which has a highly functionalized and rigid bicyclo[2.2.0]hexane core. Fragmentation of the C3–C19 bond would afford a redox-active intermediate which upon further reductive quenching would lead to the

• formation of IN1. The radical cation IN1 served as the reference point for DFT investigations. As illustrated in Figure 2a, facilitated by a favorable radical cation–π interaction [31], IN1 proceeds to the first radical addition transition state (TS1), with an energy barrier of 8.3 kcal/mol. This leads to

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• acted as nucleophile, the stable imine–gold–aryl cation–π–π interaction precluded rearrangement and promoted the capture of imine to form spiro[indoline-3,3'-pyridine] derivatives 67. The Ph3PAuCl/AgNTf2-catalyzed cyclization of N-propargyl-tethered amide enynes efficiently afforded four distinct

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• occurred to give a radical cation PhSeSePh•+ at the anode. The subsequent cleavage of Se–Se bond formed a radical PhSe• and a cation PhSe+. Further additional oxidation of PhSe• yielded another PhSe+, which worked as the major reactive species and quickly added to C≡C in 13a to form intermediate A. Finally

• phenylselenium cation C and phenylselenium radical B through radical cation species A. Simultaneously, the cathodic reduction of 17a generated anion D and radical B. Then, addition of B with the alkyne portion in 16a gave a radical intermediate E, which proceeded a one-electron oxidation followed by nucleophilic

• addition and then deprotonation to yield the desired 18a via intermediate G. Another possible pathway is that phenylselenium cation C attacked 16a afforded the alkenyl cation G, which underwent cyclization and deprotonation to produce 18a. It should be noted that this conversion proceeded under metal

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• TBS protection in one pot. Oxidation of the primary alcohol using Swern oxidation gave the hydroxy aldehyde 3, which was activated with a formal silicon cation to trigger the Prins cyclization terminated by the tertiary alcohol, affording silylated bicycle 9 directly through the designed bioinspired

• oxa-carbenium cation triggered by an acid to proceed a Friedel–Crafts reaction to afford the dibenzocyclooctene skeleton. On the other hand, eupomatilone would undergo redox transformations to generate another oxa-carbenium cation to undergo a Friedel–Crafts reaction to form a spirocyclic skeleton

• . This oxa-carbenium cation could also undergo hydrolysis to provide a linear skeleton with a hydroxy ketone moiety, and this hydrolysis process is reversible. It is worth noting that Zhou explored the chemical conversion of the eupodienone skeleton to the eupomatilone skeleton through acid-promoted

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• stabilized allyl cation intermediates that undergo regioselective trapping by internal O- and N-nucleophiles furnishing functionalized heterocycles. This method provides access to tetrahydrofuran or pyrrolidine frameworks, each bearing a trifunctionalized (E)-configured vinyl side chain. The use of a shorter

• alkynes undergo 1,2-carbofunctionalization, where the highly electrophilic Ar–M species adds to the alkyne, generating a vinyl cation intermediate [7], which typically reacts with an internal nucleophile to form five- [8][9] or six-membered rings [7][9][10] (Scheme 1A). Thus far the internal nucleophilic

• rearrangements via the 1,2-silyl shift, enabled by the β-cation-stabilizing properties of silyl groups [19][20]. This phenomenon has been successfully employed in 1,3-difunctionalization events in both intermolecular [21] and intramolecular fashion [22] (Scheme 1B). Thus far such propargylsilane rearrangements

Photochemical reduction of acylimidazolium salts

• Michael Jakob,
• Nick Bechler,
• Hassan Abdelwahab,
• Fabian Weber,
• Janos Wasternack,
• Leonardo Kleebauer,
• Jan P. Götze and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153

• photocatalyst radical anion ([PC]·−) and the DIPEA radical cation D (Scheme 1). Single-electron transfer from [PC]·− to the benzoylazolium species 1 would then regenerate the ground-state photocatalyst and afford the Breslow radical anion C, which could in turn react with D in a hydrogen-atom-transfer (HAT

• electron to compound 3 could explain the formation of the fully reduced species 2. In this case, subsequent mesolysis would generate the benzyl radical cation G, which would deliver 2 following a HAT step with the DIPEA radical cation D. To confirm whether O-benzoylated species is indeed an intermediate in

Thermodynamics and polarity-driven properties of fluorinated cyclopropanes

• Matheus P. Freitas

Beilstein J. Org. Chem. 2025, 21, 1742–1747, doi:10.3762/bjoc.21.137

• 1.2.3-c.c., it is capable of interacting with ions and potentially acting as both an anion and a cation carrier. To evaluate this property, Na+ and Cl− ions were simulated in interaction with one and two molecules of 1.2.3-c.c., forming complexes akin to a "sandwich," as illustrated in Figure 3. In

• these complexes, the cation coordinates with the fluorine atoms, while the anion interacts with the positively charged hydrogen atoms. The complexation is thermodynamically favorable when compared to the isolated species (ions and 1.2.3-c.c.), as indicated by the ΔH0 of formation: −32.5 kcal mol−1 for

Influence of the cation in hypophosphite-mediated catalyst-free reductive amination

• Natalia Lebedeva,
• Fedor Kliuev,
• Olesya Zvereva,
• Klim Biriukov,
• Evgeniya Podyacheva,
• Maria Godovikova,
• Oleg I. Afanasyev and
• Denis Chusov

Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130

• hypophosphorous acid are commercially available in bulk amounts, however, their usage is understudied in organic processes. While NaH2PO2 has proved to be an efficient four-electron reductant in the catalyst-free reductive amination, the influence of cation in hypophosphite salt has not been studied yet. This

• investigation of cation influence on the efficiency of reductive amination, a commercially available NaH2PO2, and in situ synthesized LiH2PO2, NaH2PO2, KH2PO2, RbH2PO2, and CsH2PO2 were compared. To account for the reactivity of H3PO2 as is, the reaction outcome both for the neutral XH2PO2 (where X is Li, Na, K

• has shown clear influence of the cation in the hypophosphite salt on the effectiveness of the reductive amination. The acidity of the reaction media was a key factor affecting the equilibrium in the interaction between carbonyl compounds and amines. Intermediately acidic media is the optimal for the

On the aromaticity and photophysics of 1-arylbenzo[a]imidazo[5,1,2-cd]indolizines as bicolor fluorescent molecules for barium tagging in the study of double-beta decay of ¹³⁶Xe

• Eric Iván Velazco-Cabral,
• Fernando Auria-Luna,
• Juan Molina-Canteras,
• Miguel A. Vázquez,
• Iván Rivilla and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2025, 21, 1627–1638, doi:10.3762/bjoc.21.126

• fluorescent moieties constitute promising candidates to detect Ba2+ cations [8][9] (Figure 2). Another essential component is an aza-crown ether of appropriate dimensions to capture the barium cation. In addition, one para-disubstituted phenyl (or aryl) group is installed to generate selective cation–π

• efficiency of crown ethers as components in cation-selective fluorescent probes has been extensively explored [7][30], to the best of our knowledge no previous computational DFT studies on the selectivity of crown ethers of different sizes with Ba2+ have been reported. Therefore, we explored (Scheme 2A) the

• binding between this cation and 12-crown-4 (16a, n = 1), 15-crown-5 (16b, n = 2), 18-crown-6 (16c, n = 3) and 21-crown-7 (16d, n = 4), to form Ba2+·crown ethers 15a–d. We compared the corresponding binding energies by means of the following isodesmic equation: Where the different terms correspond to Gibbs

Thermodynamic equilibrium between locally excited and charge transfer states in perylene–phenothiazine dyads

• Issei Fukunaga,
• Shunsuke Kobashi,
• Yuki Nagai,
• Hiroki Horita,
• Hiromitsu Maeda and
• Yoichi Kobayashi

Beilstein J. Org. Chem. 2025, 21, 1577–1586, doi:10.3762/bjoc.21.121

• anion of the Pe moiety. Additionally, a shoulder signal observed near 500 nm was attributed to the radical cation of the PTZ(TPA) unit. However, although previous studies selectively excited the Pe moiety and attributed the 725 nm band to the LE state of Pe moiety, such an assignment may not be directly

• attributable to the Pe radical anion and the PTZ(TPA) radical cation appeared at ≈600 and ≈500 nm, respectively (Figure 7). The electron transfer time constant was determined to be 7.6 ps, significantly slower than that of Pe–PTZ(TPA)2 (120 fs or faster), reflecting the effect of the phenyl spacer that

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• oxidative state PC1* that interacts with morpholine (8a) to generate the corresponding aminium radical cation. To gain a better understanding of the process, the formation of the enaminone product 9a was monitored overtime by 1H NMR, which confirmed that the the reaction was complete within 2 h. Furthermore

• . Simultaneously, acridinium photocatalyst PC1 absorbed energy and transitioned from the ground state to excited state under visible-light irradiation. This excited state PC1* is quenched by the amine, generating the amine radical cation and PC1 radical via a single-electron transfer (SET) process. Then, the C−Br

Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Marcin Palusiak,
• Heinz Heimgartner,
• Marta Denel-Bobrowska and
• Agnieszka B. Olejniczak

Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113

• terminal S‒CH2 position, leading to the formation of the sulfonium cation 11 and the delocalized heterocyclic anion 12 (Scheme 6). In the next step, competitive addition of both intermediate species yields either thioaminals 9 or dithioacetals 10. However, a slow isomerization of the thermodynamically less

Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

• conditions is due to a favorable formation of EWG-substituted aryl radicals from the iodonium cation, based on their reduction potentials and bond-dissociation energies calculated by Romanczyk and Kurek [45]. The reduction potential in SET reactions for iodonium salts with EWG-substituted aryls significantly