Amino acid-based surfactants: sustainable synthesis and antimicrobial mechanisms

• Rafaela Gomes Bezerra,
• Lourdes Pérez and
• Francisco Fábio Oliveira de Sousa

Beilstein J. Org. Chem. 2026, 22, 1067–1085, doi:10.3762/bjoc.22.85

• from moderate to high values depending on amino acid functionality, alkyl chain length, and purification strategy [10][37]. For structurally more complex surfactants, especially those derived from multifunctional amino acids such as lysine, arginine, and histidine, selective functionalization often

• large-scale applicability. Purification is commonly achieved by acid–base extraction, selective precipitation, salt formation, and crystallization, while chromatographic techniques are mainly restricted to laboratory-scale studies [38]. Scalable processes preferentially rely on phase separation and

Synthesis of functionalized, 13-alkyl-substituted coralyne derivatives and investigation of their interactions with duplex and abasic site-containing DNA

• Laurin Beckmann,
• Jason Lennard Kunze,
• Hannah Karola Strunk,
• Maurice Michel and
• Heiko Ihmels

Beilstein J. Org. Chem. 2026, 22, 1057–1066, doi:10.3762/bjoc.22.84

• -binding units. Specifically, we proposed that the attachment of an (aminooxy)alkyl functionality may lead to a highly selective ligand for abasic site-containing DNA (AP-DNA) [36][37]. The latter is duplex DNA with apurinic/apyrimidinic (AP) sites, more generally named abasic sites (Scheme 1). Such AP

• through oxime formation with the aldehyde functionality of ring-opened ribose [37][38]. Thus, a coralyne–(aminooxy)alkyl conjugate might offer the combination of selective covalent attachment with intercalation of the coralyne unit (Scheme 1), thus providing a more efficient blocking of the AP site, along

• inhibitor of APE1-mediated repair of AP sites. Taken together these results provide a blue-print for the development of selective coralyne-based AP–DNA ligands. Even though only one example was made available, so far, the approach may be easily varied to obtain different linker lengths and linking units, so

Synthesis of novel 1,2,4-oxadiazole-isoxazoline hybrids and their in silico potential with adenosine receptors

• Pshtiwan S. Mohammed,
• Mohammed K. S. Dalo,
• Onur C. Yazıcı,
• Muhammet Yildirim and
• Akın Sağırlı

Beilstein J. Org. Chem. 2026, 22, 1033–1047, doi:10.3762/bjoc.22.82

• processes. Technological progress has enabled the creation of highly potent and selective adenosine receptor agonists and antagonists. These refined tools allow researchers to isolate the effects of specific receptor subtypes, providing the foundation for next-generation, targeted therapies. While many of

• may contribute to drug discovery efforts by providing valuable insights for the design of more potent and selective inhibitors of the adenosine A1 receptor. ADMET studies An in silico ADMET analysis of the compounds with binding energy scores ≥ −9.5 kcal/mol (7d, 7j, 7n, 7o, 7s, 7t, 7u, 7w, 7x, 7ah

Synthesis and optical resolution of 4,5-diaminohomoadamantane: a promising scaffold for chiral ligands and bioactive compounds

• Polina A. Man’kova,
• Vadim A. Shiryaev,
• Olga S. Podlipnova,
• Marat M. Khisyamov,
• Dmitry S. Nikerov,
• Alexander N. Reznikov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2026, 22, 1013–1022, doi:10.3762/bjoc.22.80

• ). The NaBH4/MoO3 system [81] led to the selective reduction of only the hydroxyimino group, affording azidoamine 7. The reduction of azidoxime 4 using LiAlH4 [75][87] allowed total reduction of both the oxyimino and azido groups, resulting in the formation of isomeric diamines 8a,b (Scheme 2). Since 4,5

• ). In order to find a more selective method for the synthesis of trans-4,5-diaminohomoadamantane (8a), aziridine 12 was studied. When the tosyl group was replaced with a triflic group (12), only the trans-diastereomer 14 was formed in the reaction with NaN3 and NH4Cl. Upon reduction of the azido group

Z-Selective semihydrogenation of alkynes via Ni/Lewis acid synergistic catalyzed system using DMF as hydrogen source and solvent

• Lei Kang,
• Haifeng Gao and
• Luo Yang

Beilstein J. Org. Chem. 2026, 22, 1004–1012, doi:10.3762/bjoc.22.79

• dual-catalytic system has been developed for the Z-selective semihydrogenation of alkynes. Utilizing DMF as both the hydrogen donor and reaction medium, this method affords Z-alkenes in high yield with excellent stereoselectivity under mild conditions. The protocol employs cost-effective and readily

• available catalysts, and demonstrates broad applicability across a wide range of substrates. Keywords: alkynes; DMF; Ni/Lewis acid catalysis; Z-selective semihydrogenation; Introduction Z-Olefins represent important structural units in natural products, pharmaceuticals, and functional materials, making

• application in reduction chemistry [45][46]. In this work, we describe a new synergistic catalytic system for the cis-selective semihydrogenation of alkynes, utilizing a Lewis acid together with a nickel catalyst and DMF as the hydrogen source. This method achieves excellent Z-selectivity (up to 98:2 Z/E

Novel macrocycles: from synthesis to supramolecular function

• Veronica Iuliano,
• Carmen Talotta,
• Margherita De Rosa,
• Paolo Della Sala,
• Konrad Tiefenbacher,
• Pablo Ballester and
• Carmine Gaeta

Beilstein J. Org. Chem. 2026, 22, 982–985, doi:10.3762/bjoc.22.76

• rings. Importantly, the study demonstrates a pronounced size-matching effect, showing how cavity dimensions can be tuned to selectively recognize specific dicarboxylate chain lengths. Subsequently, Kato, Ogoshi, and colleagues [35] report the selective monoformylation of naphthalene-fused propellanes

• functionalization, and selective host–guest recognition properties. By organizing recent examples by internal and external stimuli, the authors outline how macrocyclic systems can regulate cargo release via supramolecular recognition and nanovalve mechanisms. The Review also discusses current challenges and future

• directions for the clinical translation of these materials. Moving from broad biomedical overviews to therapeutic applications, Consoli and co-workers [38] exploit the synthetic versatility of calix[4]arenes to develop selective anticancer systems. By clustering bioactive isothiouronium groups on an

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

• , controllable reaction manifolds that are inaccessible under thermochemical conditions. These developments position 3d metal electrocatalysis as a versatile and programmable platform for selective hydrogenation and isotopic labeling under mild, sustainable conditions. Keywords: electrochemical reduction

• conventionally achieved by exposing substrates to molecular hydrogen in the presence of homogeneous transition-metal catalysts or supported catalysts, thereby affording the corresponding alkanes. In sharp contrast, when selective reduction of alkynes is required, the use of Lindlar’s catalyst provides a

• provide effective approaches for promoting selective alkene hydrogenation. Electrochemical and 3d transition-metal catalysis Owing to the straightforwardness of the reductive chemical transformation, a plethora of synthetic approaches has been utilized, with recent efforts increasingly converging on 3d

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

• , tunable basicity, and directional hydrogen-bonding capabilities enable precise modulation of molecular recognition, biological activity, and physicochemical properties. Consequently, the efficient and selective construction of carbon–nitrogen (C–N) bonds embedded within aromatic nitrogen frameworks

• selective hydroamination chemistry. Review Copper-catalyzed aza-Michael addition Early studies on copper–amido complexes by Gunnoe The aza-Michael addition of (hetero)aromatic amines to electron-deficient olefins provides a straightforward and atom-economical route to β-amino carbonyl, β-amino sulfone, and

• in good to excellent yields. Expanding beyond the classical 1,4-conjugate addition, Lee et al. reported the highly regio- and (E)-selective copper-catalyzed aza-1,6-conjugate addition of aza-heterocycles and arylamines to sulfonyl-1,3-dienes 8 (Scheme 5) [40]. The combination of the sterically

Diastereodivergent electrophilic trapping of α-boryl lithium derivatives

• Tereza Pavlíčková,
• Noam Orbach and
• Ilan Marek

Beilstein J. Org. Chem. 2026, 22, 882–887, doi:10.3762/bjoc.22.68

• their stereoselective reactions remains challenging. Here, we examine the diastereoselective generation and trapping of α-boryl lithium species formed by ring opening of substituted iodomethylcyclopropanes. After lithium–iodine exchange and selective C–C bond cleavage, these intermediates react with a

• derivative 1 to afford product 4 as single diastereomers. Specifically, iodide 2 was subjected to tert-butyllithium (t-BuLi) in diethyl ether at −95 °C, efficiently generating cyclopropylmethyllithium 3 via lithium–iodine exchange. Subsequent selective C–C bond cleavage of 3, proceeding exclusively through

• : cyclopropane 5i possessing a chloride as a leaving group underwent highly selective cyclization to deliver the stereodefined borylated cyclopentane 6k in high 84% yield as a single diastereomer. The relative configuration of 6k was unambiguously established by X-ray crystallographic analysis of an osmylated

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