Semisynthesis, characterisation, and antibacterial evaluation of a novel lecanoric acid-derived amide library

• Ethan D. Abbott,
• Sasha Hayes,
• Jonathan M. White,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2026, 22, 1023–1032, doi:10.3762/bjoc.22.81

• the 17,000 lichen species that have been classified to date, 1,050 metabolites have been identified, half of which are unique to lichens [3][4]. Although only 10% of all lichen compounds have been subjected to bioactivity testing, several pharmacological properties have been documented [5]. Examples

• [15], and antioxidant [16] properties of this compound, albeit with low to moderate bioactivity observed. Nevertheless, we considered this compound a desirable chemical scaffold for semisynthetic studies due to its high natural abundance in the lichen species and the compound’s phenolic, ester, and

• the aromatic moiety was established through HMBC and ROESY correlations. Key COSY, HMBC, and ROESY correlations are shown below in Figure 4. Owing to the Davis group’s interest in discovering new natural products or derivatives with antibacterial properties, all compounds 1–13 were assessed via a

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

• based on a rigid polycyclic framework such as homoadamantane remain underexplored. We anticipated that the unique steric and lipophilic properties of chiral trans-4,5-diaminohomoadamantane could provide the necessary stereoinduction in metal-catalyzed asymmetric reactions. In addition, such structures

• been of interest to organic chemists for many years. Such a simple and symmetric structure as adamantane is widely used in pharmaceutics to obtain drugs with a wide spectrum of action, as well as to improve the properties of drugs currently in use [1][2][3][4][5][6][7]. The chemistry of adamantane has

• been extensively studied [8][9][10][11][12][13][14][15][16], while the properties of homoadamantane, its closest homologue, have not been studied so thoroughly. Chemical transformations of homoadamantane both at the bridgehead [17][18][19][20][21][22][23] and at the C-4 positions [24][25][26][27][28

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

• flexibility and directional non-covalent interactions, thereby dictating assembly pathways and material properties. The results establish a correlation between spacer length and assembly propensity, with the longest spacer (C6) consistently promoting aggregation more effectively than the intermediate analogue

• -assembly; spacer length; Introduction Short self-assembling peptides are an eminent class of materials used in supramolecular chemistry due to their advantageous properties such as facile synthesis, programmable molecular information [1][2][3][4], structural diversity [5][6], biocompatibility [7][8][9

• modulate the self-assembling properties of short peptides through directional and cooperative non-covalent forces [25][26]. Coupling these to the N-terminus of the peptide sequence leads to the formation of peptide amphiphiles with a general architecture of a hydrophobic tail attached to a hydrophilic

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

• ], resorcinarenes [7], and cucurbiturils [8] emerged as some of the most extensively investigated classes of macrocyclic hosts. Their widespread popularity was driven by their straightforward functionalization and unique structural properties. In contrast to first-generation receptors, such as crown ethers [2

• to tune binding properties, guest inclusion kinetics, and physical behavior. As a result, modern macrocyclic host–guest systems now operate at the interface of materials science and chemical biology. Given the rapid development of this research area, we organized this thematic issue entitled “Novel

• 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

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

• ) voltammetry revealed that hydrogen evolution reactivity is strongly dependent on the electronic properties of the ligand environment (Scheme 8B). Notably, this electronic modulation is directly reflected in the rate constant for Co(III)–H formation. Catalysts bearing electron-withdrawing substituents exhibit

• envisioned for further advancing the field. In particular, expansion to other 3d transition metals represents an important opportunity, as the diverse redox properties and coordination environments accessible across the 3d series may enable fundamentally new reactivity patterns and mechanistic regimes that

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

• (MRI) [4][5] and as spin probes for Overhauser MRI in vivo [6]. Piperidin-1-oxyls played a key role in the development and industrial implementation of controlled polymerization of vinyl monomers (nitroxide-mediated polymerization, NMP) [7]. The unique redox properties of these radicals underpin their

• nitroxide-mediated polymerization (NMP), because shielding with ethyl or bulkier alkyl groups decreases accessibility of the nitroxide moiety and improves the equilibrium parameters in the reversible trapping of alkyl radical of the growing polymer chain [11]. This shielding also alters the redox properties

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

• , while suppressing the competing 1,4-addition pathways commonly observed in copper-catalyzed amination reactions. Recently, Lee et al. reported the copper-catalyzed hydroamination of allylic sulfones 10 (Scheme 6) [41]. By tuning the steric and electronic properties of the NHC ligands (e.g., IPrCuCl vs

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

• -resolution imaging. Among them, probes 4a and 4b, corresponding to HMSiR-Halo and AzeHMSiR-Halo originally reported by the Urano and Xu groups [30][32][33][34], respectively, are widely used fluorophores for single-molecule imaging because of their excellent spontaneous blinking properties. Accordingly, the

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

• , 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

• /or engineering to achieve the desired specificity. As a general guideline, the final choice depends on multiple factors, including protein properties (sequence, flexibility, post-translational modification status, stability) and reagents availability (commercial reagents, in-house preparations, 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

• electronic aspects such as photoluminescence and the spectroscopic and reactivity properties of gold(III) hydrides, before moving on to trans-influence enabled insertion reactions and catalytic applications. Perspective General considerations “Trans-influence” is a term applied to the weakening or

• naturally focused on the assessment of the ligand influence in linear compounds. For example, in 1977 Jones and Williams correlated the 35Cl nuclear quadrupole resonance of LAuCl complexes with the electronic properties of L, for a series of alkyl and arylphosphines, phosphites, isocyanides, N-donors and Cl

• trying to determine. Caution is therefore required in interpreting crystallographic bond lengths, and it is important to eliminate such factors by resorting to calculated bond distance data. Ligand structures and properties For the exploration of the reactivity and catalytic applications of gold(III

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

• -withdrawing nature of the S=O group. The second redox stage characterizes the transformation of the sulfoxide fragment and is observed in most cases at 1.82–1.91 V. The radical-scavenging activity and antioxidant properties of the unsymmetrical sulfoxides and their precursor thioethers were evaluated using

• activities and unusual physicochemical properties, which render them useful in various fields of chemistry. Catechol-containing compounds, in particular, are known for their antioxidant activity through the regulation of free-radical processes [1][2], and are used as antiparkinsonian [3][4][5], antitumor

• , imparting resistance to various solvents [9][10]. Furthermore, catechol-containing compounds can serve as antioxidant biomimetic additives in lubricants [11]. One effective approach for the fine-tuning of polyphenol properties is functionalization via the introduction of heteroatoms (S, Se, Te) [12][13][14

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

• products’ structure, physicochemical properties and coordination behavior (for 4,5-derivative). Both 4,5- and 1,8-diazafluorenes reacted with di(pyrid-2-yl)ketone forming di(pyridin-2-yl)methylene)-9H-4,5-diazafluorene (4,5-DPDAF) and 9-(di(pyridin-2-yl)methylene)-9H-1,8-diazafluorene (1,8-DPDAF) in 54

Halogenated azobenzene acrylates: from efficient solution photoswitching to stable solid-state photochromic materials

• Martina Vachtlová,
• Michaela Fecková,
• Vítězslav Zima,
• Jan Podlesný,
• Milan Klikar,
• Oldřich Pytela,
• Patrik Pařík,
• Jakub Opršal,
• Eliška Juhaňáková,
• Veronika Chrtová and
• Filip Bureš

Beilstein J. Org. Chem. 2026, 22, 782–794, doi:10.3762/bjoc.22.60

• halogenated azobenzene acrylate monomers bearing fluorine, chlorine or bromine substituents is reported. The monomers were prepared via a facile three-step synthetic route involving azo-coupling, O-alkylation and O-acylation. Apart from the steady electrochemical properties, halogen substitution proved to be

• a very useful tool to tune the thermal and optical properties, light-induced switching in particular. Monohalogen derivatives exhibited up to 93% E → Z photoconversion efficiency in solution, whereas the efficiency of dihalogen analogues is lower by 20%, which is ascribed to their nonplanar

• for over 90 days. These findings demonstrate that ortho-halogenation is a powerful tool for tuning the properties of photoresponsive materials for potential applications in colorimetric thermal sensing and light-controlled functional systems. Keywords: azobenzene; E/Z isomerization; halogen

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

• systems or the phenyl ring at the 3-position of the isoxazole to enhance hydrophilicity and improve pharmacokinetic properties [42]. Co-crystallization of GS-4997 with ASK1 unveiled key stabilizing interactions in the active site. Specifically, the amide carbonyl forms a hydrogen bond with the backbone

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

• CNS-active properties, showing promise for the treatment of conditions such as Parkinson’s disease [2]. Compounds containing the imidazo[1,2-a]pyridine core have also shown potential as anti-infective agents, with some compounds showing activity against Streptococcus pneumoniae (3) [3], tuberculosis

• derivatives have been found to be of interest in the development of organic materials with interesting properties [11][12]. The importance of imidazo[1,2-a]pyridines is evidenced by the plethora of recent review articles covering methods for their preparation [13][14][15][16] and functionalisation reactions

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

• the aromatic ring. In this way, we intend to assess the effect of these properties on the biological activity. Additionally, by comparing RLIT results obtained for this new series of castasterone (2) with those obtained for teasterone (3) [30] and 3-dehydroteasterone (3-DT, 3a) [31] analogs, it would

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

• diastereoselectivity (>20:1) and enantioselectivity (89–96% ee) regardless of the electronic and steric properties of the aromatic ring in the α-(arylimino)ester (Scheme 4). However, when using other dipolarophiles, such as dimethyl maleate, tert-butyl crotonate, and tert-butyl cinnamate, a noticeable decrease in

• absence of interaction between the metal and the electron-withdrawing group of the dipolarophile, and the coordination properties of the metal, for example, the possibility of changing the coordination sphere of copper(I) from bidentate to monodentate, which does not occur with the Ag(I) atom, which has

• reactions. Due to their unique chemical properties and high versatility, fullerenes are finding increasing application in organic synthesis. In this work, the authors focused on the functionalization of C60 with a helicene component via Cu(II)/L13-catalyzed enantioselective 1,3-dipolar cycloaddition of

Anti-invasive and cytotoxic evaluation of a (+)-pinoresinol-based semisynthetic library against glioblastoma

• Chen Zhang,
• Kah Yean Lum,
• Jonathan M. White,
• Paul I. Forster,
• Nicholas Booth,
• Sunita A. Ramesh and
• Rohan A. Davis

Beilstein J. Org. Chem. 2026, 22, 691–704, doi:10.3762/bjoc.22.54

• reported. In this study, we chemically investigated the seeds of Eremophila maculata for the first time, which led to the isolation and characterization of two known plant metabolites, (+)-salicifoliol and (+)-pinoresinol. Due to the reported biological properties of the lignan natural product

• spectrometric techniques. Plants are a vast reservoir of phytochemicals that serve as the source of numerous drugs, including many with anticancer properties [18][19]. These phytochemicals may act on cellular signalling, apoptosis, metabolic pathways, and cell motility in tumor cells. Most anticancer research

• cells represent a powerful approach that can augment current therapies, prevent metastasis, and improve patient quality of life and survival. Cytotoxicity is defined as the ability of a compound to cause cell death, while anti‑invasive properties refer to the ability of compounds to slow down or block

Harnessing light energy with molecules

• Grace G. D. Han,
• Mogens Brøndsted Nielsen and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2026, 22, 680–682, doi:10.3762/bjoc.22.52

• trisNBD-benzene, overcoming the signal overlap that limits conventional 1H NMR analysis. Further, the consequences on the absorption properties, photoisomerization, and QC lifetime were studied. In another article by Krappmann and Hirsch [6], the implications of replacing the methylene bridge of the NBD

• . Systematic tuning of photochromic properties is the focus of several articles in this thematic issue. Kitagawa, Kobatake, and co-workers [15] studied the effect of the substitution position of aryl groups on the thermal back-reaction of azadiarylethene photoswitches. Simeth and co-workers [16] present a

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

• drug targets, serving as rich inspiration for designing small molecule inhibitors which can recapitulate key binding interactions while improving pharmacokinetic properties. With the rapid advancement of artificial intelligence capabilities including powerful generative models, there is significant

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

• ligands targeting CRBN have better drug-likeness properties, including lower molecular weight, fewer hydrogen bond donors in their structures, and fewer rotatable bonds [124]. However, in addition to influencing the physical and chemical properties of molecules, according to many relevant research results

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

• construct S13 displayed measurable binary binding in the absence of the degrader architecture. Although the ligand–linker analogue showed encouraging biophysical and structural properties, the six full PROTACs did not induce detectable CK2 degradation under the conditions tested. Several mechanistic factors

Computational prediction of C–H hydricities and their use in predicting the regioselectivity of electron-rich C–H functionalisation reactions

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2026, 22, 603–610, doi:10.3762/bjoc.22.46

• regioselectivity of various C–H functionalisation reactions and machine learning (ML) models have been developed for both properties [1][2][3][4][5]. In contrast, C–H hydricities have received considerably little attention. However, the insertion into, or H-abstraction from, innately electron-rich C–H bonds are

• . Machine Learning The feature descriptor Recent research shows that the atomic descriptors introduced by Finkelmann et al. [24][25], using charge model 5 (CM5) atomic charges [26], is an excellent representation of atoms in molecules as the feature descriptor for ML models to predict various properties

• . These properties encompass the site of metabolism [25][27], the strengths of hydrogen bond donors and acceptors [28][29][30], the regioselectivity of electrophilic aromatic substitution reactions [10], C–H pKa values [3], and electro- and nucleophilicity [31]. Building on the methodology from Finkelmann

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

• . Proteolysis-targeting chimera (PROTAC) is a chemical molecule which induce the target protein to approach the ubiquitin protein through the ubiquitin proteasome system, then it can be ubiquitinated and degraded [26][27][28]. This drives to form degraders through the unique properties of their own degradation