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

• sampling. Their translational power is evident from the success of biotherapeutics: antibody–drug conjugates (ADCs), in which cytotoxic payloads covalently linked to targeting antibodies, are at the forefront of cancer therapy, delivering tumour-selective killing for improved patient outcomes; Neulasta, an

• While numerous native-sequence protein-modification tools exist with many being site-specific, few can fulfil all the aforementioned criteria simultaneously. Cysteine modification is among the most effective strategies due to the high reactivity of the thiolate, enabling selective chemical

• sodium periodate (Scheme 2a) [13], selective modification of glutamate using Rapoport’s salt (4) which has generated modified trastuzumab in moderate yield (67%; Scheme 2b) [14], or pyridoxal phosphate (PLP, 5)-mediated carbonyl formation at residues such as serine, threonine, glycine, alanine, or

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

• why CO insertion into the Au–aryl bond was not observed [60]. Bidentate Au(III) hydride complexes The selective protolytic cleavage of an Au–C bond in C^N^C complexes with a strong acid [61], or the displacement of pyridine in C^C^N hydrides by H−, leads to hydride complexes supported by bidentate C^N

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 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

• . The total synthesis commenced with the preparation of the orthogonally protected monosaccharide building blocks 1–4 (Scheme 1). Galactoside 1 was synthesized starting from the β-selective glycosylation of thioglycoside 5 [30] with aminopentyl linker 6. This reaction was promoted by N-iodosuccinimide

• linkages and the selective manipulation of long oligosaccharide chains, were successfully overcome using orthogonally protected building blocks. The resulting conjugation-ready oligosaccharides bearing aminopentyl linkers provide direct access to glycan microarray screening and in vivo immunological

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

• condensed bis-spirooxindole framework. Conclusion The condensation of isatin with ethylenediamine is strongly governed by stoichiometry, allowing selective access either to a diiminoisatin 24 or to the unexpected pentacyclic bis-spirooxindole 25 (Scheme 4) which was unambiguously identified by comprehensive

Synthetic study of vic-bromination of diarylacetylenes, easy purification and separation

• Akane Togo,
• Hiyono Suzuki,
• Yuto Akai,
• Makoto Matsumoto,
• Yoshinori Suzuma,
• Hidehiko Kodama and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2026, 22, 795–802, doi:10.3762/bjoc.22.61

• -osaka, Osaka 577-0056, Japan 10.3762/bjoc.22.61 Abstract E-Selective bromination for diphenylacetylene was established by using the combination of NBS and FeBr3 in CH2Cl2. In addition, easy purification and separation from the crude product were found. When the crude product was treated with heptane

• reported studies suggest that it is surprisingly difficult to obtain the E isomer selectively (Scheme 1). For selected examples, Espenson and co-workers reported in 1999 that E-selective bromination of diphenylacetylene took place by using H2O2, NaBr, and AcOH in the presence of MTO (methyltrioxorhenium

• -diphenylethylenes (Scheme 1c) [5]. Previous studies reported the selective synthesis of (E)-1,2-dibromo-1,2-diphenylethylene and related compounds, but Br2 or expensive reagent, which was difficult to handle, was often used [6][7][8][9][10][11][12][13][14][15]. Based on these research backgrounds, we have also been

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

• of the minimal pharmacophores of the selective FXR agonist GW4064 and the selective ASK1 inhibitor selonsertib (GS-4997) [35][36][37]. Published structure–activity relationship (SAR) studies have identified the isoxazole moiety and terminal carboxylic acid of GW4064 [38], along with the 4

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

• -toluenesulfinate to dibenzalacetone (Scheme 5). Diadducts 25 and 27 were isolated as inseparable 3:2 and 4:3 mixtures of diastereomers, respectively. From these experiments, we observed the following: 1) double conjugate addition of methanesulfinate occurs readily, such that selective preparation of monoadduct 24

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

• silver-catalyzed asymmetric double 1,3-dipolar cycloaddition reaction was developed that provides highly substituted, enantioenriched pyrrolizidines 9 containing up to six stereocenters (Scheme 8). It is assumed that the endo-selective (3 + 2) cycloaddition of the azomethine ylide obtained from

• sulfone, cinnamic, croton, and methacrylic aldehydes, and β-nitrostyrene as dipolarophiles. Depending on the dipolarophile used, pyrrolizidines 11 were obtained with an enantiomeric excess of up to 94% and yields of up to 92%. In 2009, Wang and co-workers reported the catalytic endo-selective

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

• compounds 1, 2, and 3 is depicted in Scheme 1 [40][41][42]. We envisioned that by selective oxidation at C5, compound 1 could be directly obtained from casbene (4). The macrocyclic casbane-type skeleton could be produced by an engineered heterologous host harboring both casbene synthase (CS) and an

• 3, respectively, in a more efficient and selective way by protein engineering, we thought that germacrene A (5), whose terpene cyclases are widely found in different organisms [52], could serve as a precursor for synthesis of both 2 and 3 via a transannular cyclization process [37][53][54]. A

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

• extensively in this review. For instance, selective degraders of CDK isoforms are advancing through early-phase trials [33], with molecules like BSJ-03-123 and others showing promise in hematologic malignancies by exploiting the subtle structural differences among the highly homologous CDK family members to

• ability to target the degradation of CDK6, and proteomics results also show that compound 2 has no degradation effect on CDK4. In 2020, Benowitz and co-workers carried out a project to explore the impact of different E3 ligands on the selective degradation of CDK4/6 [57]. In their research, they designed

• PROTACs for the selective degradation of CDK6 [60]. They also constructed a PROTAC-CP 10 (6) containing a triazole-containing linker to connect palbociclib and pomalidomide. Compound 6, a selective CDK6 degrader, showed good selectivity in U251 cells (DC50(CDK6) = 2.1 nM; DC50(CDK4) > 100 nM) and the

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

• ][29] and Rh [30][31] have shown to allow the selective transformation of formic acid into H2 and CO2 with high turnover frequencies (TOFs). In most cases, addition of a base (either amines or formate salts) is required to obtain high catalytic activity. Efficient systems based on inexpensive metals

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

• adjacent to the ATP-binding site of CK2α [5][6]. Fragment-based ligand discovery subsequently enabled the development of CAM4066, a selective inhibitor that simultaneously engages the αD and ATP sites. CAM4066 validated the αD region as a tractable and selective binding pocket for CK2 kinase inhibition

• potent and selective PROTAC targeting CK2 might be valuable in the evaluation of specific degradation of CK2 as a therapeutic approach. Herein, we report the design and synthesis of a series of CK2-targeting PROTACs. CAM4066 was selected as the warhead to enable CK2-specific target engagement. We

• geometry, and E3 ligase selection. Conclusion In summary, we have developed a modular synthetic platform for the construction of CK2-targeting degraders 23–26, 28, and 29 based on the selective bivalent inhibitor CAM4066. Structure-guided design enabled identification of a solvent-accessible exit vector

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

Design and synthesis of an erdafitinib-based selective FGFR2 degrader

• Yumeng Jin,
• Shidong Wang,
• Sihan Pan,
• Shuqi Huang,
• Weichen Zhou,
• Xiaohao Huang,
• Lei Zheng and
• Lingfeng Chen

Beilstein J. Org. Chem. 2026, 22, 583–591, doi:10.3762/bjoc.22.44

• -selective degrader, and for the first time confirmed its ability to degrade the membrane-bound form of FGFR2. This work provides an innovative targeted protein degradation strategy for the treatment of FGFR2-driven tumors and holds significant potential for clinical application. Keywords: CRBN; erdafitinib

• ; FGFR2; selective degrader; Introduction Fibroblast growth factor receptors (FGFR) are a family of single-pass transmembrane receptor tyrosine kinases (RTKs) localized on the cell surface that bind to fibroblast growth factors [1][2][3]. Dimerization and autophosphorylation of FGFRs are induced by their

• cholangiocarcinoma [16][17][18]. Accordingly, research into therapeutics targeting FGFR2 has emerged as a major focus. To treat FGFR2-driven tumors, current research primarily focuses on two distinct classes of inhibitors, namely FGFR pan-inhibitors and FGFR2-selective inhibitors. Among these in Figure 1

Continuous-flow carbonyl hydrogenation under subatmospheric to atmospheric hydrogen pressure enabled by robust heterogeneous Pt–Fe catalysts

• Hiroyuki Miyamura,
• Ryosuke Kajiyama,
• Shun-ya Onozawa,
• Yoshihiro Kon and
• Shū Kobayashi

Beilstein J. Org. Chem. 2026, 22, 575–582, doi:10.3762/bjoc.22.43

• often suffers from insufficient reactivity and conversion, even under harsh reaction conditions, such as high temperature and pressurized hydrogen, or when employing advanced technologies [8][9][11][12]. The selective hydrogenation of carbonyl moieties often needs to overcome the problem of

• overreduction of other functionalities like aromatic systems, and requires additives to suppress this unwanted side-reaction [6][10]. We have developed heterogeneous bimetallic nanoparticle catalysts for the selective hydrogenation of quinizarin to leucoquinizarin under continuous-flow conditions [30]. During

• our mechanistic study, we unexpectedly discovered that Pt–Fe bimetallic nanoparticles immobilized on a composite support of dimethylpolysilane (DMPSi) and alumina (Pt‒Fe/DMPSi–Al2O3) exhibited extraordinary catalytic performance for the selective hydrogenation of ketones under continuous-flow and

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

• attached phosph(on)ate anions as powerful new hosts for the amino acids lysine and arginine. In the recent past, we demonstrated that the affinity and selectivity of our lysine-selective molecular tweezers could be improved by attaching natural peptide recognition elements. This could be documented in

• various projects with tailored peptide tweezer conjugates: For example, the self-complementary ELTLGEFL sequence of the nuclear export signal in survivin was coupled to tweezers which rendered them selective for this important interface (NMR evidence, 1:1 stoichiometry, K/A mutants) and prevented the

• selective for accessible lysine residues was covalently connected to the histone H3 peptide at various distances to add the released lysine inclusion energy (Kd ≈ 10 µM) and reach nanomolar affinity. Azidopeptides were conjugated to butynyl tweezers by click chemistry and subjected to competitive

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• , Nicolaou and co-workers merged both building blocks within a Ni(II)/Cr(II)-catalyzed NHK reaction using chiral ligand 206 (Scheme 23) [95]. Upon treatment with DBU, 3-methylenetetrahydrofuran 201 was obtained in 56% yield over two steps. PMB-deprotection, iodination and selective reduction of the ester

• allylation, 280 was isolated as a single diastereomer upon recrystallization. The dihydroxylation, oxidative cleavage and reduction with NaBH4 afforded diol 281, whose primary alcohol unit was protected enabling the selective oxidation towards ketone 283. Olefination with 293 (Nysted reagent) and

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

• selective remediation strategies. Supramolecular materials, with their pre-organized structures, offer a promising route for uranium removal. Phenoxycalix[4]pyrroles (PCP) are well-known supramolecular scaffolds capable of selective metal binding, making them attractive candidates for designing uranium

Recent advances in the stereoselective synthesis of distal biaxially chiral molecules

• Fanxing Zhou,
• Chen Zhang,
• Lingyu Sun,
• Yiyun Fang,
• Siming Zheng,
• Lina Hu,
• Mengyang Shen,
• Zhen Zhao,
• Wei Xu,
• Yunqiang Sun and
• Zi-Qiang Rong

Beilstein J. Org. Chem. 2026, 22, 461–479, doi:10.3762/bjoc.22.34

• biaxial terphenyl atropisomers with chlorinated and brominated variants to achieve high diastereo- and enantioselectivity. The process takes place via a two-step kinetic resolution. In 2021, Shi and co-workers reported a highly trans-selective synthesis of axially chiral styrenes 76 containing a

• hydrocarbons. Catalytic synthesis of biaxial triphenylene block-transfer isomers. A Pd(II)-catalyzed trans-selective C–H alkenylation strategy through thioether-directed olefination. Synthesis of N-arylphthalimides from prochiral maleimides and NHC-activated dienolides. Ni-catalyzed synthesis of triaxially

Structural reassignment of compound 968, an allosteric glutaminase inhibitor

• Lindsey A. Albertelli,
• Sainabou Jallow,
• Chun Li and
• Scott M. Ulrich

Beilstein J. Org. Chem. 2026, 22, 455–460, doi:10.3762/bjoc.22.33

• reaction with 2-naphthol as the dinucleophile is also known [32]. In all cases, the regiochemistry of cyclization is selective and no isomeric products are formed. Conclusion In this report, we confirm the finding by Martinez [28] and Kozlov [29][30] that the three-component reaction originally claimed to

Synthesis and stereochemical analysis of dynamic planar chiral oxa[7]orthocyclophene

• Yukiho Hashimoto,
• Yuuya Kawasaki,
• Kazunobu Igawa and
• Katsuhiko Tomooka

Beilstein J. Org. Chem. 2026, 22, 436–442, doi:10.3762/bjoc.22.30

• -substituted oxacyclophene 1ad We planned to construct the nine-membered cyclic ether skeleton of 1ad in the final step by an intramolecular Williamson etherification of haloalcohol 2 (Scheme 1). The iodine-substituted Z-alkene moiety of 2 was planned to be introduced through a trans-selective hydroiodination

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

• strategy similar to that described above for the preparation of calixarenes 24–26 involving nitration of calix[4]arenes followed by selective reduction of the nitro groups could not be implemented for the preparation of p-aminocalix[4]arenes bearing 2-azidoethyl groups at their narrow rims. To overcome

• hampering or preventing a catalytic hydrogenation of these compounds. On the other hand, in calixarenes 31 and 32, which are immediate products of the selective reduction of the nitro groups in compounds 29 and 30 under neutral or basic conditions, the free amino groups may be alkylated by a neighboring

Design, synthesis and biological evaluation of 2,5-diaryloxazolo[4,5-d]pyrimidin-7-ylamines as selective cytotoxic agents against HeLa cells

• Maryna V. Kachaeva,
• Agnieszka B. Olejniczak,
• Marta Denel-Bobrowska,
• Victor V. Zhirnov,
• Yevheniia S. Velihina,
• Stepan G. Pilyo and
• Volodymyr S. Brovarets

Beilstein J. Org. Chem. 2026, 22, 390–398, doi:10.3762/bjoc.22.27

• , 7, and 9 were selective against the tested lines. Compound 9 can be classified as the most attractive and promising candidate for further development against cervical adenocarcinoma. Keywords: ADMET analysis; anticancer activity; 2,5-diaryloxazolo[4,5-d]pyrimidin-7-ylamines; Introduction Purine

• activity. They combine purine-like recognition features with the synthetic flexibility of heterocycles, offering a platform for selective targeting of tumor-related enzymes and receptors. Tumor cells overexpress kinases, DNA/RNA polymerases, and metabolic enzymes that bind purine nucleotides. Cancer cell

• oxazolopyrimidine derivatives may demonstrate selective cytotoxicity against cancer cell lines like HeLa, HepG2, A549, and central nervous system (CNS) tumor models [1][2][3]. The introduction of heterocyclic molecules with different amino groups as hydrogen-bond donors (and sometimes acceptors via lone electron

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

• enables selective oxidative hetero-coupling followed by dehydrative cyclization, furnishing the extended [8]helical scaffold efficiently under mild, oxidant-free conditions. Structural analyses show retained aromaticity, increased helical distortion, and higher configurational stability (≈38 kcal/mol

• designed coupling partners to control both chemo- and regioselectivity. A finely tuned anodic sequence enables selective oxidative hetero-coupling followed by dehydrative cyclization, delivering extended [8]helical scaffolds efficiently under mild, oxidant-free conditions. Combined experimental and DFT