The role of spacer length and flexibility in peptide self-assembly

• Julian Link,
• Albin Lahu,
• Manfred Wagner,
• Tanja Weil and
• David Y. W. Ng

Beilstein J. Org. Chem. 2026, 22, 986–996, doi:10.3762/bjoc.22.77

• -terminus on a chlorotrityl (Clt)-resin according to the general procedure described in the experimental section. To synthesize the C6 and C3-spacer variants, C6-Nap-ICA 6 and C3-Nap-ICA 7, the free amine of H2N-Ile-Cys-Ala-Clt-resin was functionalized with the naphthalene imides 3 and 4, respectively

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

• designed protection and functionalization sequences, the authors introduced orthogonal reactive groups at opposite rims of the macrocycle. The synthetic versatility of these systems was demonstrated by copper-catalyzed “click” reactions and amine-based transformations, yielding highly functionalized

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

• storage for controlling regioselective C–C bond formation beyond semihydrogenation chemistry [125]. In 2025, the Wang group reported a nickel electrocatalytic system featuring a bifunctional ligand equipped with a pendant amine, specifically designed to promote Ni–H formation while simultaneously

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

• nitroxides 7a–d in 50–80% overall yield from piperidines 5a,b (Scheme 3). The structures of nitroxides 7a–d were confirmed by 1H NMR spectroscopy of their amine derivatives, obtained via Zn/CF3COOH reduction in CD3OD, following a reported procedure [37]. The full line-shape analysis of the 1H NMR spectra for

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

• valuable in hydroamination chemistry. Several distinct yet interrelated activation modes have been identified for copper-catalyzed alkene amination [27]. Copper frequently participates directly in amine activation via the formation of Cu–N species (Scheme 1a) [30][31]. In the presence of a base and

• been widely explored. Among the various catalytic systems, copper catalysts have attracted particular attention owing to their ability to activate amine components by forming copper–amido species. In this activation mode, deprotonation of the N–H bond generates a Cu–N intermediate with enhanced

• , and α,β-unsaturated carbonyl compounds, to afford the corresponding β-amino products 3 in excellent yields (up to 99%). This method exhibited high functional group tolerance on aromatic amine substrates, including those with electron-donating and electron-withdrawing substituents, without

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

• HaloTag amine using HATU/DIPEA as the activation system. This strategy afforded three high-performance fluorescent probes 4a, 4b, and 4c, in overall yields of 62%, 37%, and 46%, respectively. The absorption and emission spectra of 4a, 4b, and 4c (Figures S1–S3 in Supporting Information File 1) showed

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

• ) with 4-fluorobenzaldehyde (2a, Ar = 4-FC6H4) was carried out in MeCN in the presence of various bases. When using amine-type bases soluble in acetonitrile, such as Et3N and DMAP, the reaction did not occur (the outcome of the reaction was monitored by TLC), whereas the use of TMG or DBU resulted in

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

• asymmetric Michael reactions between β-substituted α,β-unsaturated ester 1a and benzophenone-imine of glycine tert-butyl ester 2a in the presence of 20 mol % of CSB-1 and other chiral tertiary amine catalysts including quinine, levamisole, (+)-sparteine (Scheme 1). To our disappointment, the results showed

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

• of proteins are linear polypeptide chains, possessing a single N- and C-terminus and hence presenting these regions as attractive targets for site-specific modification. Indeed, over 80% of protein termini are solvent-exposed and chemically accessible [5]. Notably, the N-terminal amine and C-terminal

• reagent, 1) was used to label the α-amino group of insulin during sequence determination (Scheme 1a). Its selectivity over lysine’s ε-amine originates from the low pKa of the N-terminus, influenced by the adjacent carbonyl group and systematically characterized at ≈6–7 (Scheme 1b) [7]. Building on this

• 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

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

• amide of Val 757, and concurrently, a triazole nitrogen engages in a hydrogen bond with the amine moiety of Lys 709 [43]. By merging the key pharmacophores of the two drugs and systematically optimizing the resulting bipharmacophoric structure, we ultimately obtained balanced dual-target modulators

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

• 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

• . Compound 9f was also successfully converted into 13f under the conditions shown in Table 1. Nenajdenko et al. reported a few examples of the preparation of imidazo[1,2-a]pyridin-3-amine ethyl esters starting from ethyl glyoxylate in toluene and using ammonium chloride as a catalyst in yields of 30–35% [26

• successfully subjected to reductive amination conditions to give the desired amine products 8a–d (Scheme 8). To the best of our knowledge, this is the first reported synthesis of aldehydes 20 and products of reductive amination, such as 8. Conclusion A method for the preparation of 3-(alkylamino)imidazo[1,2-a

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

• dissociation of the amine nitrogen of L9 from the Cu(I) center in the transition state F leads to a change in regioselectivity and the formation of cycloadduct 17 [46]. A similar catalytic system was successfully used for the asymmetric (3 + 2) cycloaddition of azomethine ylides with trisubstituted

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

• those previously reported for other Cu/amine systems under similar reaction conditions [44][45][46][47]. The influence of the nature of the amine was next studied (Table 2). In the absence of the amine, no conversion was observed (Table 2, entry 1). When aniline was used, a slight improvement of the

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

• closest to this opening was therefore identified as the optimal site for structural modification. To allow more flexible functionalisation, the linking region was redesigned to introduce a secondary amine adjacent to the original amide position. This amine maintained the length and orientation of the

• problems [6]. The ATP-site binder and αD-site binder fragments were prepared using literature procedures from the original development of 1. The modified linking portion containing the new secondary amine was incorporated into the general assembly 2 to afford a CAM4066-derived scaffold suitable for PROTAC

• suitable for linker installation, and introduction of a secondary amine at this position provided a versatile handle for downstream functionalisation. The resulting CAM4066-derived ligand–linker analogue S13 retained high-affinity binding to CK2α and preserved the characteristic bivalent binding mode in co

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

• growth factor receptor 2 (FGFR2) to overcome the issues of drug resistance and adverse reactions associated with traditional inhibitors in the treatment of FGFR2-driven tumors. Erdafitinib was employed as the targeting ligand, and its aliphatic amine site was conjugated with a CRBN E3 ligase ligand to

• purpose the clinically validated inhibitor erdafitinib as a POI binder that selectively targets FGFR2. Based on the analysis of the co-crystal structure of erdafitinib bound to the FGFR kinase domain (PDB: 5EW8, https://doi.org/10.2210/pdb5EW8/pdb) [30], we observed that the aliphatic amine group is

• positioned in the solvent-exposed region of the molecule. Given this observation, we selected the aliphatic amine group as a suitable conjugation site (Figure 2a). Previous studies have shown that different linkers exhibit distinct selectivity profiles [31]. Therefore, in this study, novel FGFR2 degraders

Experimental and DFT studies on the regioselective methanolysis of 5-azido-9-oxabicyclo[6.1.0]nonan-4-yl 4-nitrobenzoate isomers

• İlknur Polat,
• Selçuk Eşsiz and
• Emine Salamci

Beilstein J. Org. Chem. 2026, 22, 547–556, doi:10.3762/bjoc.22.40

• methodologies for the preparation of this class of compounds are of considerable interest. Azides have traditionally been used as protected primary amine equivalents. Therefore, in our previous studies, we employed azides containing eight-membered rings as precursors in the synthesis of C8-aminocyclitols [12

Get a better glimpse on sequential photoreactions of trisnorbornadienes with ¹⁹F NMR spectroscopy

• Julian Felix Maria Hebborn,
• Ben Eric Merten,
• Thomas Paululat and
• Heiko Ihmels

Beilstein J. Org. Chem. 2026, 22, 527–534, doi:10.3762/bjoc.22.38

• ]. Upon addition of magic blue (5, 7.5 mol %) to a solution of quadricyclane 2f0,3 in CDCl3, the norbornadiene 1f was formed almost quantitatively in addition to very small traces of tri(4-bromophenyl)amine, i.e., the reduced catalyst (see Supporting Information File 1, Figure S12). Discussion A

Synthesis of a HDAC inhibitor–nanogold probe for cryo-EM visualization in class I HDAC co-repressor complexes

• Wiktoria A. Pytel,
• John W. R. Schwabe and
• James T. Hodgkinson

Beilstein J. Org. Chem. 2026, 22, 480–485, doi:10.3762/bjoc.22.35

• functionalized this position with linkers for the development of HDAC1–3 proteolysis targeting chimeras (PROTACs) [14][18]. Alkyl-linker lengths of approximately 12 atoms and greater were the most effective degraders [18]. We chose the commercially available amine functionalized nanogold particles (Au–NH2

• -labeled HDAC inhibitors could serve as effective fiducial markers in cryo-EM, facilitating the localization of distinct subunits or binding sites within large and flexible multiprotein complexes. HDAC1–3 inhibitor CI-994; HDAC inhibitor–nanogold probe Au–(CI-994); structure of amine-functionalized 1.4 nm

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

• groups from the 5-position to the 6-position to prevent N-acetylation-related side effects and enhance antitumor efficacy [38][39]. Notably, a series of naphthalimide derivatives bearing sulfur-containing secondary or tertiary amine functions at the 6-position of naphthalimide have gained attention, as

• secondary amino functions strongly suppress acetylation and the embedded sulfur function contributes to the apoptosis induction [40][41].The third modification route centres on functional group engineering, in which small amine substituents are replaced with polyamines or long aliphatic chains, thereby

• with water (20 mL) and brine (20 mL). The organic layer was dried with anhydrous MgSO4, filtered and the solvent was evaporated under vacuum. Petroleum ether was added to the residue and triturated. The solid was filtered, affording white amine 11 (500 mg, 48%). mp: 95–97 °C; 1H NMR (400 MHz, CDCl3) δ

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

• ]arenes containing four amino groups at the wide rim and one, two or four propargyl or 2-azidoethyl groups at the narrow rim of the macrocycle, which can be used for expanding functionalization of the calixarene core in the well-known amine acylation (or similar reactions) and CuAAC ‘click’ reactions. Two

• tetraureacalix[4]arenes was obtained. Examination of the 1H NMR spectra of the tetraureas in CDCl3 showed that in most cases triazole heterocycles do not intervene the formation of homo- and heterodimeric capsules by these compounds. Thus, considering the synthetic value of CuAAC and amine transformations, p

• bis(trimethylsilyl)amine (HMDS) with n-butyllithium in THF immediately before the addition of a propargylated calixarene followed by TBSCl. This allowed us to improve the yield of the known calix[4]arene 6 [9] having four silylated propargyl groups at the narrow rim, and to obtain the respective

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

• , and the Strecker amine (aminoethylamine) moieties. Cytisine has been shown to inhibit the proliferation of A549, HepG2, EC109, K562, HL-60, and U937 cells. Following a 48 h treatment, IC50 values were approximately 2 mM in HL-60 and U937 cells, whereas higher concentrations were required to inhibit

• combination of the [1,3]oxazolo[4,5-d]pyrimidin-7-amine fragment (structures A and B) with cytisine, glucamine, and aminoethylamine represents a promising strategy for the rational design of multifunctional hybrids with improved biological activity, water solubility, lower toxicity and target engagement

• described methods [14][15][16] as depicted in Scheme 2. The 7-Amino-substituted 1,3-oxazolo[4,5-d]pyrimidines 1–9 were obtained with high yields (65–80%) by the reaction of 2,5-diaryl-7-chloro-1,3-oxazolo[4,5-d]pyrimidines II with the corresponding amine (aminoethylamines [17], cytisine and N-methyl-ᴅ

Dialkylaminoalkylation of β-ketosulfones via ring-opening of 3-sulfonylpyrrolidines

• Evgeny M. Buev,
• Alexander V. Pavlushin,
• Vladimir S. Moshkin and
• Vyacheslav Y. Sosnovskikh

Beilstein J. Org. Chem. 2026, 22, 383–389, doi:10.3762/bjoc.22.26

• field is offering diverse methodologies that enable the introduction of either protected nitrogen atoms or aliphatic amine groups. Such diversity has greatly expanded the synthetic arsenal available for constructing aminomethylated compounds. In contrast, methods allowing an aminoethylation process is

• cesium carbonate at 25 °C for 96 h provided higher yield (Table 1, entry 2, 70%). However, heating this mixture at 65 °C for 24 h in a sealed vial gave pure desired 4-methoxy-N,N-dimethyl-3-(phenylsulfonyl)butan-1-amine (4a) in 90% yield and 83% overall yield starting from ketosulfone 1a (Table 1, entry

• solution of dimethylamine did not affect the process and bis-dimethylamino product 4l was readily isolated in 97% yield. The obtained 2-(phenylsulfonyl)butane-1,4-diamines 4l–p represent the biogenic amine putrescine scaffold, incorporating dialkylamino or azaheterocyclic motifs such as pyrrolidine

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

• unsymmetrical oxaza[8]helicenes Building on Zhang’s facile acid-mediated carbazole synthesis [53], in which aniline derivatives react with p-benzoquinone to afford 3-hydroxycarbazoles [54], we employed a closely related substrate. Specifically, N-(p-tolyl)phenanthren-3-amine (2) – prepared from 3

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

• that coordination of the amide oxygen to the Lewis-acidic sites of Nb activates the amide toward nucleophilic attack. Simultaneously, water is pre-adsorbed on the basic oxygen sites of Nb2O5, enabling nucleophilic attack on the activated carbonyl center (D). Following amine release from the resulting

• hydrogen chloride acting as a Lewis acid, enabling nucleophilic attack by the amine to form a tetrahedral intermediate Z. Subsequent intramolecular hydrogen shift, followed by elimination of dimethylamine, affords the protonated transamidation product. In 2021, Lee et al. discovered that carbon dioxide

• reacted smoothly with p-methoxyphenyl (PMP) amine, p-methoxybenzyl (PMB) amine, N-benzyl-N-methylamine, and indole, generating the corresponding amides 99–102 in good to excellent yields. Based on kinetic studies, the authors proposed a plausible mechanism in which the dihydrogen tetrametaphosphate

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