Electrochemical reduction of unsaturated carbon–carbon bonds via 3d transition-metal catalysis

• Geon Kang,
• Minki Jeon,
• Pooja Kumari Jat,
• Cheoljae Kim and
• Isaac Choi

Beilstein J. Org. Chem. 2026, 22, 955–981, doi:10.3762/bjoc.22.75

• presence of Cp2Co, indicating that Fe(I) is not merely a transient species but is accumulated under the operating conditions via a mediator-driven uphill electron transfer. Importantly, this Fe(I) species was shown to be catalytically competent, as exposure to tolane and benzoic acid resulted in the

• ) species. In the presence of the in situ generated silane, a Ni–H species is proposed to form, although its involvement remains to be fully established [90]. Substrate scope studies demonstrated that not only terminal alkenes bearing free carboxylic acid or hydroxy groups, but also substrates containing

• under conditions in which both the redox mediator and the cobalt catalyst are simultaneously operative. Kinetic analysis revealed positive dependence on the concentrations of acid, alkyne, mediator, and cobalt catalyst, supporting a mechanistic regime in which substrate and acid binding equilibria

Synthesis of sterically shielded piperidine nitroxides via acid-catalyzed heterocyclization of β-aminoketone derivatives with ketones

• Mark M. Gulman,
• Yurii I. Glazachev and
• Sergey A. Dobrynin

Beilstein J. Org. Chem. 2026, 22, 948–954, doi:10.3762/bjoc.22.74

• in materials science and structural biology. The new heterocyclization strategy implies the construction of a 2,2,6-trisubstituted piperidine scaffold from β-aminoketone acetals and dialkyl ketones under acid catalysis. The resulting amines were oxidized to the corresponding ketonitrones and

• of sterically hindered piperidine nitroxyl radicals. Six-membered cyclic nitrones – 2,2,6-trialkyl-substituted 2,3,4,5-tetrahydropyridine-1-oxides were prepared via the acid-catalyzed reaction of 2-(2-aminoalkyl)-2-methyl-1,3-dioxolanes with ketones in analogy to literature procedures [25][26][27][28

• ), the N-adjacent methine (2.71 ppm), and diastereotopic methylene protons (1.39, 1.58 ppm) supported the assigned structure. Compound 4b exhibited spectral data identical to those previously described [31]. The aminodioxolanes 4a,b were subjected to acid-catalyzed heterocyclization with the

Recent advances in copper-catalyzed direct hydroamination of alkenes with (hetero)aromatic amines

• Hyejeong Lee and
• Yunmi Lee

Beilstein J. Org. Chem. 2026, 22, 925–947, doi:10.3762/bjoc.22.73

• , including copper–amido-mediated nucleophilic addition or aminocupration, Lewis acid-type alkene activation, and radical-mediated pathways. These complementary mechanisms provide access to diverse alkene classes with control over regioselectivity (Markovnikov vs anti-Markovnikov addition), stereoselectivity

• –amido intermediate or aminocupration-type pathways, enabling efficient C–N bond formation under relatively mild conditions. Copper species may also operate in a Lewis acid-type capacity, where coordination to the alkene or copper-derived Brønsted acidity generated in situ increases alkene

• the direct hydroamination of alkenes using aromatic amines and aza-heterocyclic N–H nucleophiles under copper catalysis. The primary focus is on the mechanistic paradigms, Cu–amido pathways, Lewis acid activation, and carbon-radical manifolds, and on how these distinct activation modes translate into

A practical CO₂-mediated synthesis of 5,6-carboxylated silicon-rhodamines for targeted probe development

• Dongjie Hou,
• Shaowei Wu,
• Ning Xu,
• Pengjun Bao,
• Wenhao Jia,
• Qinglong Qiao and
• Zhaochao Xu

Beilstein J. Org. Chem. 2026, 22, 915–924, doi:10.3762/bjoc.22.72

• carboxylation strategy using CO2 as an inexpensive, readily available, and non-toxic C1 source. In principle, CO2 can serve as a carbonyl source through nucleophilic addition followed by protonation to furnish the corresponding carboxylic acid. On the basis of this design (Figure 2a), brominated SiR precursors

Cascade transformation of 2-(diazoacetyl)-2H-azirines to 2-aroyl-3-hydroxy-1H-pyrroles via condensation with aromatic aldehydes

• Timur O. Zanakhov,
• Ekaterina E. Galenko,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2026, 22, 897–904, doi:10.3762/bjoc.22.70

• [4.1.0]heptan-5-one derivative. The acid-catalyzed transformation of which leads to 2-aroyl-3-hydroxy-1H-pyrroles. Keywords: azirines; condensation; cyclization; diazo compounds; pyrroles; Introduction Diazo compounds play a significant role in the synthesis of heterocyclic compounds, which explains

• bicyclic intermediate 4. This acid-catalyzed transformation leads to 3-hydroxy-2-aroyl-1H-pyrroles 5 (Scheme 1). To the best of our knowledge, only few examples of such compounds have been so far reported [23][24]. Results and Discussion A test reaction of 2-(2-diazoacetyl)-3-phenyl-2H-azirine (1a, R = Ph

• mixture containing 4a (after separation of Cs2CO3) with TsOH at 100 °C or MsOH at 25 °C, with the acid clearly acting as a catalyst. Other protic acids, such as aq HCl, aq HI, and TFA, as well as a Lewis acid (FeCl3), also facilitated the conversion of 4a to 5a. Meanwhile, resinification of the reaction

Chiral cyclopropenimine-catalyzed enantioselective Michael reactions of phenol and benzofuran-derived α,β-unsaturated pyrazolamides with benzophenone-imine of glycine esters

• Ya Bai,
• Xue-Ying Wang,
• Si-Kai Zhu,
• Yan-Ting Shen,
• Sheng-Yong Zhang and
• Ping-An Wang

Beilstein J. Org. Chem. 2026, 22, 888–896, doi:10.3762/bjoc.22.69

• (Lambert catalyst, CSB-1) as an organocatalyst. In the presence of 20 mol % CSB-1, the Michael adducts were obtained in up to 85% yield and 98% ee under mild conditions. The configurations of these Michael products were deduced by X-ray single crystal diffraction of a pyroglutamic acid ester containing two

• adjacent stereocenters, which was obtained from in-situ acidic hydrolysis and lactamization of the corresponding Michael product. Keywords: α,β-unsaturated pyrazolamide; chiral cyclopropenimine; glutamic acid; lactamization; Michael addition; Introduction Phenols and benzofurans are feedstock chemicals

• , dronedarone, saprisartan and so on [3]. Therefore, the introduction of benzofuran to organic molecules plays an important role in drug research and development. Compounds containing glutamic and pyroglutamic acid frameworks (Figure 1) indicate many pharmacologic properties including influence on protein

Site-specific labelling of native peptides and proteins: chemical and enzymatic strategies

• Antonio Angelastro,
• Jonathan Bargh,
• Subhajit Guria,
• Victor Laserna and
• Louis Luk

Beilstein J. Org. Chem. 2026, 22, 857–881, doi:10.3762/bjoc.22.67

• -like linkages (≈9 M−1 s−1; Scheme 1d) [10], whereas 2-formylphenylboronic acid 3 (FPBA) generates thiazolidino boronate with noticeably improved kinetics (103 M−1 s−1; Scheme 1e) [11][12]. Aldehydes can be introduced at protein N-termini through several strategies: oxidation of serine or threonine with

• biological environment [46]. In a related concept, the Chin group reported the genetic incorporation of the unnatural amino acid 2,3-diaminopropionic acid (DAP, 13), a nucleophilic amine that has a relatively low pKa (6–8) and is structurally analogous to serine or cysteine, enabling identification of native

• ], whereas tosylation is one of the few procedures compatible with red blood cells and animal labelling [51]. Alternatively, benzophenone 18, which can be incorporated in the form of an unnatural amino acid, can form a UV-induced diradical for protein modifications (Scheme 7b) [52][53][54][55]. Proteins

The trans-influence in gold chemistry from a catalytic perspective

• Manfred Bochmann

Beilstein J. Org. Chem. 2026, 22, 838–856, doi:10.3762/bjoc.22.66

• be underestimated. For example, cleavage of one of the Au–phenyl bonds in A (Scheme 2) with a strong acid provides access to the gold borane and silane σ-complexes [(C^N–CH)Au(C6F5)(H–X)]+, X = B(O2C2Me4) or SiEt3 (Scheme 3) [32]. In the presence of traces of moisture, the Au(III)+ Lewis acidity may

• chemical reactivity. For example, 8a proved stable to air, water and acetic acid, although stronger acids like trifluoroacetic lead to decomposition due to protolytic cleavage of one of the Au–phenyl bonds [31][32]. The stabilising effect of the N-donor in C^N^C ligands is seen quite generally and leads to

• into gold hydrides by stepwise O-transfer reactions to phosphine (Scheme 6) [55]. Quite a different mechanism for the conversion of Au–OH into Au–H was found by Goldberg and co-workers for the hydrogenolysis of [(P^C^P)AuOH]+, which requires an acid catalyst [56]. A mechanistically similar heterolytic

Unsymmetrical sulfoxides with sterically hindered catechol fragment: synthesis, structure, electrochemical properties, and antiradical activity

• Daria A. Burmistrova,
• Vasiliy A. Fokin,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Maxim V. Arsenyev,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2026, 22, 828–837, doi:10.3762/bjoc.22.65

• the reaction with the 2,2′-diphenyl-1-picrylhydrazyl radical (DPPH) and the 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS+•). In both assays, the lowest IC50 values among the studied catechol sulfoxides were found for compounds bearing isopropyl and tert-butyl substituents

• , the oxidation of catechols is facilitated under alkaline conditions. Therefore, the oxidation of thioethers 1–7 was carried out in the presence of acetic acid (Scheme 1). This approach proved successful for the selective oxidation of the thioether group, and no products arising from oxidation of the

Total synthesis of the capsular polysaccharide repeating unit towards the development of a glycoconjugate vaccine against Klebsiella pneumoniae ST512

• Shuo Zhang,
• Ondřej Daněk and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2026, 22, 821–827, doi:10.3762/bjoc.22.64

• . Key synthetic challenges including the stereoselective construction of the 1,2-cis glycosidic linkage on the galacturonic acid core and the inherently low reactivity of elongated oligosaccharide intermediates were addressed employing orthogonally protected building blocks. The resulting library of

• repeating unit {3)-[α-ʟ-Rhap-(1→4)]-α-ᴅ-GalpA-(1→2)-α-ʟ-Rhap-(1→2)-α-ʟ-Rhap-(1→2)-α-ʟ-Rhap-(1→3)-β-ᴅ-Galp-(1→}n (Figure 1) [13]. The chemical synthesis of this molecule is challenging due to the stereoselective formation of the 1,2-cis glycosidic linkage on the galacturonic acid core. In addition, the

• (NIS) and trifluoromethanesulfonic acid (TfOH) to afford 7 in 86% yield, neighboring participation effect of the levulinoyl (Lev) group at C2 position provided only the β-product. The linker was introduced in anticipation of conjugation to a carrier protein or a glycan microarray surface [31

Synthesis and structural elucidation of a novel bis-spirooxindole from isatin and ethylenediamine

• Irene Moreno-Gutiérrez,
• Josefa L. López-Martínez,
• Sonia Berenguel-Gómez,
• Irene Torres-García,
• Duane Choquesillo-Lazarte,
• Manuel Muñoz-Dorado,
• Miriam Álvarez-Corral and
• Ignacio Rodríguez-García

Beilstein J. Org. Chem. 2026, 22, 813–820, doi:10.3762/bjoc.22.63

• -platinum module. Mass spectra were recorded in a Waters Xevo LC-QTof-MS with electrospray ionization. The AQ:AcN mixture (50:50, 0.1% formic acid) was used as eluent. X-ray diffraction data were collected on a Bruker AXS SMART APEX diffractometer. Structure solution and refinement were carried out using

Knoevenagel condensation of 4,5- and 1,8-diazafluorenes

• Darya S. Cheshkina,
• Christina S. Becker,
• Alina A. Sonina and
• Maxim S. Kazantsev

Beilstein J. Org. Chem. 2026, 22, 803–812, doi:10.3762/bjoc.22.62

• malononitrile or acetonitrile derivatives [14][19][20]. However, the use of diazafluorenes as the methylene component in condensation reactions remains underexplored. These reactions can be carried out under basic [13][21], acidic [3][5] or Lewis acid catalysis [15][22], but the corresponding literature

• examples are scarce, especially for 1,8-diazafluorene. We have previously reported the condensation of 4,5-diazafluorene (1) with aromatic aldehydes and dialdehydes under ammonium acetate catalysis in acetic acid giving the corresponding products in good yields [5][23]. Remarkably, the only condensation of

• conditions were moderate and the reactivity of aldehydes was insufficient it seemed reasonable to increase their activity by converting them into iminium cations through treatment with ammonium acetate in the presence of acetic acid (Scheme 2). Initially, the Knoevenagel condensation of 1 and 2 was carried

Design, synthesis, and biological evaluation of FXR/ASK1 dual-target modulators

• Xi Zhang,
• Jingyan Wang,
• Ziqiang Zhao,
• Caiyi Wang,
• Zenghui Ye,
• Wei-Yuan Ma,
• Jian-Xing Xu and
• Fengzhi Zhang

Beilstein J. Org. Chem. 2026, 22, 771–781, doi:10.3762/bjoc.22.59

• remain limited. Presently, resmetirom, a THR-β agonist, stands as the sole pharmacotherapy to have received approval, thus underscoring the critical and as yet unmet medical need in this domain [6]. The farnesoid X receptor (FXR), a bile acid-activated nuclear receptor highly expressed in the liver and

• intestine, is a key regulator of genes involved in cholesterol and bile acid homeostasis, hepatic gluconeogenesis, lipogenesis, inflammation, and fibrosis. It has been demonstrated that the substance under discussion also helps to maintain intestinal barrier integrity, to prevent bacterial translocation

• , and to support a balanced gut microbiota [7]. In view of this pleiotropic role, FXR activation has emerged as a well-established pharmacological target for MASH [8]. Consequently, a diverse range of FXR agonists – categorized as bile acid derivatives, non-bile-acid steroidal agonists, non-steroidal

Preparation of 3-(alkylamino)imidazo[1,2-a]pyridine-2-carbaldehydes via Kornblum oxidation and unexpected ring-opening reactions of the corresponding alcohols under oxidative conditions

• Sandile J. Mkhize,
• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2026, 22, 763–770, doi:10.3762/bjoc.22.58

• ]pyridine-2-carbaldehydes is reported. A Groebke–Blackburn–Bienaymé reaction between 2-aminopyridine derivatives, cyclohexyl isocyanide and glyoxylic acid in the presence of methanol and an acid catalyst gave the 2-ester derivatives that were reduced to give the corresponding alcohols. Mild Kornblum

• GBB reaction was performed using a suitably substituted 2-aminopyridine 9a–e, cyclohexyl isocyanide (10) and glyoxylic acid monohydrate (11) in the presence of 0.1 equiv HClO4 (relative to aminopyridine) to afford the imidazo[1,2-a]pyridin-3-amine product 12 unsubstituted at position 2 (Scheme 1

• ), using conditions described by Gladysz et al. [24]. Reaction with glyoxylic acid as the aldehyde component has previously been reported to yield the 2-unsubstituted product as a result of in situ decarboxylation [25]. Unexpectedly, on product isolation we discovered that compounds 13a–d, the methyl

Synthesis and biological evaluation of new brassinosteroid analogs with C-22 benzoate function

• María Núñez,
• Camila Escobar,
• Mario Párraga,
• Mauricio Soto,
• Luis Espinoza-Catalán,
• Katy Díaz and
• Andrés F. Olea

Beilstein J. Org. Chem. 2026, 22, 753–762, doi:10.3762/bjoc.22.57

• , abscisic acid and gibberellin do not cause BES1 accumulation [47], therefore this assay is accurate and complements the biological tests performed above. Thus, in this study, the Western blot analysis was used to detect BES1 in presence of different exogenously applied BR analogs (12, 14 and 17–22). The

• of the signaling process. Structures of natural occurring brassinosteroids. Structures of C-22 benzoate-functionalized brassinosteroid analogs 4–14 and 17–22 prepared from the known precursor 16 [29], analog 16a [29] and structure of starting material 23,24-bisnor-5-cholenic acid 3β-acetate (15

• new BR analogs 17–22, from 23,24-bisnor-5-cholenic acid 3β-acetate (15). Conditions: a) p-R-PhCOCl/CH2Cl2/py, DMAP, rt, 2 h, 96.7%, 78.0%, 91.2%, 95.3%, 95.6%, and 93.6% yields for 23–28, respectively. b) DHQD-CLB, CH3SO2NH2, K2CO3, K3[Fe(CN)6], OsO4, t-BuOH/H2O (1:1 v/v), rt, 36 h, 77.8%, 67.9%, 65.8

Rongalite addition to dienones: diastereoselectivity in cyclic sulfone synthesis; stereochemical rationalization and prospects as a general conjugate nucleophile

• Melina Goga,
• Hao Zong,
• James Franco,
• Jazmine Prana,
• Rudolph Michel,
• Antonia Muro,
• Elana Rubin,
• Janet Brenya,
• Henk Eshuis and
• Magnus W. P. Bebbington

Beilstein J. Org. Chem. 2026, 22, 742–752, doi:10.3762/bjoc.22.56

• high concentration of ≈80% acetic acid (pH ≈3), it seemed plausible that activation of the dienone carbonyl group would occur by hydrogen-bonding, rather than complete proton transfer to the carbonyl oxygen lone pairs [29]. We therefore included explicit solvation with acetic acid in our computational

• 1b. Minimized structure of dienone 7 (calculated using the PBE0 functional [26] and the def2-SVP basis set [27] (see Supporting Information File 1 for full computational details)). Modeling of cyclization transition states (the solvating acetic acid molecules were omitted for clarity, and the

Synthesis of heterocycles based on azomethine ylides from α-amino acids (or amines) and carbonyl compounds

• Ekaterina V. Berezhnaya,
• Alexander I. Ponyaev,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2026, 22, 705–741, doi:10.3762/bjoc.22.55

• pyrrolizidine alkaloids with diverse biological activity [6][7][8]. An analysis of experimental and review articles showed that (3 + 2) cycloaddition reactions are carried out, in most cases, using two main strategies for obtaining azomethine ylides, depending on the amino acid derivative used: a free amino

• acid or its ester (Scheme 1). In both cases, condensation of amino acids with carbonyl compounds occurs; however, in the first case, decarboxylation occurs with the in situ formation of azomethine ylides, which subsequently undergo cycloaddition to unsaturated substrates. The advantage of the first

• multicomponent one-pot (3 + 2) cycloaddition reactions involving azomethine ylides from isatins and amino acids [21][35]. The main feature of this review is that we have attempted to consider all currently known systems for generating azomethine ylides based on carbonyl compounds and amino acid derivatives (or

Synthesis of depressin, cryptomeridiol and 4-epi-cryptomeridiol enabled by a terpenoid chiral pool-producing platform

• Yao Kong,
• Tao Wang,
• Chen Wang,
• Pengcheng Zhang,
• Yuanning Liu,
• Kaibiao Wang,
• Fen Liu,
• Hongli Jia and
• Zhengren Xu

Beilstein J. Org. Chem. 2026, 22, 683–690, doi:10.3762/bjoc.22.53

• hydroxy group allowed the synthesis of compound 1 from 4 in nine steps. Selective acid-mediated 5,10-transannular cyclization of 5 followed by hydration reaction furnished both products 2 and 3 in two steps. Keywords: chemoenzymatic synthesis; chiral pool; isopentenol utilization pathway; terpene

• condensation of dimethylallyl pyrophosphate (DMAPP) with different numbers of isopentenyl pyrophosphate (IPP) [6]. Two naturally existing pathways, i.e., the methylerythritol phosphate (MEP) pathway and mevalonic acid (MVA) pathway, as well as artificially designed pathways, such as the isopentenol utilization

• pathway, have been adopted to provide the two key five-carbon building blocks DMAPP and IPP. With the recent advancement in the field of synthetic biology, more chiral terpenes (e.g., guaia-6,10(14)-diene [7][8], drimenol [9][10], and ent-atiserenoic acid [11] as shown in Figure 1b) became easily

Using generative AI to transform peptide hits into small molecule leads

• Joshua Mills and
• Yu Heng Lau

Beilstein J. Org. Chem. 2026, 22, 672–679, doi:10.3762/bjoc.22.51

• fails to yield hits [9]. While the term peptidomimetics has been used to describe a variety of molecular classes, including modified peptides and molecular scaffolds for display of amino acid side-chains, this Perspective focuses on non-peptidic small molecules with the appropriate shape and

• translation (also known as RaPID, random non-standard peptides integrated discovery [4]). Key interactions that comprise the pharmacophores were experimentally determined by alanine scanning and other amino acid substitutions to explore SAR, coupled with analysis of co-crystal structures obtained for the

• bound complexes, including computational analysis of the amino acid interactions (SiteMap [16]) and hydration in the binding pocket (grid inhomogeneous solvation theory [17] in AmberTools [18]). The pharmacophores were then used as the basis for virtual screening with docking (Glide [19][20]) to obtain

Photoorganocatalytic trifluoromethylation of (het)arenes in green conditions

• Egor N. Boronin,
• Svetlana E. Kaurkina,
• Milena M. Svetlakova,
• Anton S. Bolshakov,
• Maxim V. Arsenyev,
• Vasilii F. Otvagin,
• Alexey Yu. Fedorov,
• Timothy Noël and
• Alexander V. Nyuchev

Beilstein J. Org. Chem. 2026, 22, 662–671, doi:10.3762/bjoc.22.50

• ) under blue-light irradiation in acetonitrile (Scheme 1d) [17]. Also, photoelectrochemical trifluoromethylation procedures using trifluoroacetic acid or its salt were published recently [18][19]. Inspired by these methodologies, we sought to combine their advantages to develop a metal- and base-free

• originally reported by Bazyar and Hosseini-Sarvari [20]. A comparison of the atom efficiencies of various CF3 sources clearly indicates that trifluoroacetic acid (TFA) is the most atom-efficient and, moreover, the least expensive CF3 source (Table 1). Although iodotrifluoromethane, triflyl chloride, and the

• Langlois and Ruppert–Prakash reagents formally exhibit higher atom efficiencies than trifluoroacetic anhydride (TFAA), they are significantly costlier and challenging to prepare. In contrast, trifluoroacetic acid generated as a by-product can be readily converted back into TFAA, especially in large-scale

Advantages of PROTACs in achieving selective degradation of homologous protein families

• Luxi Yang,
• Xinfei Mao,
• Jingyi Zhang,
• Jing Shu,
• Wenhai Huang,
• Xiaowu Dong,
• Yinqiao Chen and
• Mingfei Wu

Beilstein J. Org. Chem. 2026, 22, 628–661, doi:10.3762/bjoc.22.49

Hydrogen production from formic acid catalyzed by NHC–Cu complexes

• Orlando Santoro and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2026, 22, 620–627, doi:10.3762/bjoc.22.48

• 289, 9000 Gent, Belgium 10.3762/bjoc.22.48 Abstract The first NHC–Cu-catalyzed decomposition of formic acid (FA) is reported. In the presence of PhSiH3, only hydrogen is generated while CO2 is captured by a silane species. The decomposition of an equimolar mixture of FA and an amine provided an

• equimolar mixture of H2 and CO2. The efficiency of the catalysis showed to be strongly dependent on the nature of the amine. Keywords: copper N-heterocyclic carbene; formic acid dehydrogenation; hydrogen storage; metal hydride; silanes; Introduction The discovery and utilization of alternative and

• realization of a hydrogen economy [6][7]. Amongst the various H2 sources investigated to date, formic acid (HCO2H, FA) is considered one of the most promising. Indeed, FA contains 4.4% H2, is inexpensive and is liquid under ambient conditions, thus easy to handle and transport. In addition, the CO2 generated

Towards the targeted protein degradation of CK2: design and synthesis of CAM4066-based PROTACs

• Sophie Day-Riley,
• Sona Krajcovicova,
• Aryaman Raj Sokhal,
• Jan L. Venne,
• Paul Brear,
• Marko Hyvönen,
• Benjamin C. Whitehurst,
• Jason S. Carroll and
• David R. Spring

Beilstein J. Org. Chem. 2026, 22, 611–619, doi:10.3762/bjoc.22.47

• undesired alkylation of the base and significantly improved the isolated yield up to 84%. Introduction of an acetic acid handle was then achieved via alkylation with bromoacetic acid under DIPEA mediation, giving intermediate 6, which served as the common attachment point for linkers 7–10 (for full

• corresponding triflate using triflic anhydride, followed by Suzuki–Miyaura cross-coupling with phenylboronic acid to give 16 in 59% yield (Scheme 1). Boc removal from intermediates 11–14 enabled attachment of the αD binder aldehyde 16 via reductive amination. Interestingly, NaBH(OAc)3 had performed well in the

• yield acid S13. Isothermal titration calorimetry (ITC) revealed that S13 bound CK2α with a dissociation constant (Kd = 600 nM) comparable to that of CAM4066 (350 nM; Figure 1C). This indicated that the exit vector modification and linker installation were well tolerated. Co-crystallisation of S13 with

Regioselective approach to 5-arylsulfonylisoxazoles and their antimicrobial activity

• Artem S. Sazonov,
• Dmitry A. Vasilenko,
• Denis V. Porfiriev,
• Yuri K. Grishin,
• Rimma A. Gazzaeva,
• Alisa P. Chernyshova,
• Maxim A. Kryakvin,
• Anna A. Baranova,
• Vera A. Alferova and
• Elena B. Averina

Beilstein J. Org. Chem. 2026, 22, 592–602, doi:10.3762/bjoc.22.45

• nucleophilic aromatic substitution with thiophenols followed by oxidation with m-chloroperbenzoic acid (mCPBA). The scope of the reactions was explored, demonstrating high yields across a variety of functional groups and substituents. Optimized conditions enabled selective oxidation of thioaryl groups to

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

• ) calcium ion with amino acid side chains – that might also be in part be responsible for the lack of tweezer binding to Lys-121 – but also represents a new binding mode for the tweezer moiety. The (hydrated) Ca2+ ion is apparently too large to enter the cavity of the tweezer ring, in contrast to larger Cs

• 2b on K-121 leaves more room for stabilizing packing effects. Lys-122 is also located in the vicinity of the H3-T3ph binding site; although it forms a protein contact with Asn-118, there is plenty of room around it in the crystal structure (Figure 4). However, to target this amino acid, the linker