Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• transition metal that has seen extensive use in radical chemistry is titanium. Titanium(III) complexes can function as Lewis acids but can also generate carbon-centered radicals via SET to an organic substrate. In an example from Lin and co-workers, a chiral titanium catalyst promoted enantioselective

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• heterocyclic scaffolds, which established a versatile platform for synthesizing structurally diverse indoline frameworks. Ligand-controlled cyclization of 1,n-enynes The core function of catalyst ligands lies in their ability to precisely modulate catalyst performance through electronic and steric effects. The

• ligands could enhance catalytic activity and efficiency while enabling fine control over chemo-, regio-, stereo-, and enantioselectivity of reactions. Ligands enhance both the thermal/chemical stability and solubility profiles of catalysts in specific reaction media. Thus, ligands function as a regulatory

• reaction. Catalyst-controlled cyclization of 1,n-enynes The core function of a catalyst lies in providing a new, energetically more favorable pathway for the reaction. Different catalytic systems, with their unique physical structures, chemical compositions, and electronic properties, could form distinct

Research towards selective inhibition of the CLK3 kinase

• Vinay Kumar Singh,
• Frédéric Justaud,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Blandine Baratte,
• Thomas Robert,
• Stéphane Bach,
• Chada Raji Reddy,
• Nicolas Levoin and
• René L. Grée

Beilstein J. Org. Chem. 2025, 21, 2250–2259, doi:10.3762/bjoc.21.172

• phosphotransferases (called the human kinome) involved in specific signaling pathways which regulate cell functions (e.g., metabolism, cell cycle progression, cell adhesion, vascular function, and angiogenesis). Therefore, the dysregulation of protein kinase enzymatic activity, induced by genetic alterations as well

• last 25 years and more than 400 orally effective protein kinase inhibitors are in clinical trials worldwide [4][5]. However, and despite this high interest, the function in human biology of approximately one third of the kinase members is poorly understood [6]. These enzymes are classified as “dark

• linker between the core of the inhibitor and the acidic function. The acid could be placed in meta or para positions taking into account the flexible backbone of lysine 241 (Figure 3). Further, in case the binding of these new targets would require a little more flexibility around the basic skeleton, we

Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• . Each function used a scan time of 0.5 s. Data were acquired in the continuum mode. Instrument mass accuracy calibration was verified using sodium formate. The system was controlled with a MassLynx v4.2 SCN996 software. 8-Hydrazino-2,4-dimethyl-2H-1,2,3-benzothiadiazine 1,1-dioxide (5a). To a mixture of

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• . Lipases commonly share typical sequences of α-helices and β-strands and possess a catalytic triad consisting of serine (Ser), histidine (His), and aspartate (Asp) or glutamate (Glu). These three amino residues function as a nucleophile-base–acid catalytic system to facilitate esterification, and the

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• successful execution of this approach and the demonstration of biological function of the resulting reactive probes. Results and Discussion We prepared five α-diazoamide substrates bearing S(VI) electrophiles (Scheme 1 and Table 1) [15]. Initially, three amines – morpholine, 4-phenylpiperidine and

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• the amine group would function as the catalytic unit for the Knoevenagel reaction, while the hydroxy group would serve as a handle through which we would tune the lipophilicity of the catalyst. Recently, we found that isopropyl isocyanate reacts preferentially at the DPG hydroxy groups of KSU-1 [46

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• 2023, Zhang and colleagues [109] constructed a tumor microenvironment (TME)-activated supramolecular nanoplatform (Figure 8) which was consisted of a pillar[5]arene-based amphiphilic polymer (POPD), a phototherapeutic agent (Cy7-CN), an antimalarial drug with respiratory function (atovaquone, ATO), and

• -DM) or fingolimod (FTY720) in vitro. Upon local administration, the hypoxia-responsive self-assembling peptide hydrogel resulted in improved motor function and reduced inflammation in vivo. Recently, Geng and colleagues created additional binding sites by modifying the upper rim of CA4 with glucose

Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• analogously from ester R-3d. Thus, Alloc was validated as non-expensive and relatively small N-protecting group, removal of which is compatible with double bond and acetal function of amides S-5 and R-5. The removal of the Pd catalyst at laboratory scale was done by chromatography. For large scale synthesis

Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• function [16][17]. Malassezione (1, also referred to as malathidone [18]) is an AHR agonist [19][20]. Recently, in an effort to identify compounds as glucokinase activators to treat type 2 diabetes, structure-based virtual screening identified malassezione as a potential glucokinase activator [21

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• ][12][13][14] and the nucleoside antibiotic tunicamycin [15][16][17], etc. These molecules play essential roles in cell signaling, host–pathogen interactions, and pathogenesis and, being the constituent of pathogen-associated molecular patterns (PAMPs), can function as critical virulence factor [7][18

• donors [65][66], care must be taken, and glycosylation conditions optimized to avoid the formation of oxocarbenium ions from TMS-glycosides intended to function as glycosyl acceptors. In this case, the ketoses 49 and 52 formed the oxocarbenium ions more readily due to stabilization by their alkyl

Continuous-flow-enabled intensification in nitration processes: a review of technological developments and practical applications over the past decade

• Feng Zhou,
• Chuansong Duanmu,
• Yanxing Li,
• Jin Li,
• Haiqing Xu,
• Pan Wang and
• Kai Zhu

Beilstein J. Org. Chem. 2025, 21, 1678–1699, doi:10.3762/bjoc.21.132

• literature reported by Marziano et al. [63], the introduction of the Mc function allows the activity coefficients-based rate equation to be reformulated as Mc function-correlated rate equation, explicitly linking sulfuric acid acidity to reaction rates. Therefore, the linearized integrated form for kinetics

• analysis can be obtained from the Mc function-correlated rate equation. The linearized equation requires prior determination of two key parameters: (i) the acidity function Mc and (ii) the concentration ratio of , to resolve the values of k* and n. According to the works of Marziano et al. [64][65][66

• ], quantitative correlations between the Mc function and both sulfuric acid concentration and temperature could be established. The values of are governed by both temperature and sulfuric acid concentration. The experimental determination of across varying temperature and H2SO4 concentrations has been widely

Structural analysis of stereoselective galactose pyruvylation toward the synthesis of bacterial capsular polysaccharides

• Tsun-Yi Chiang,
• Mei-Huei Lin,
• Chun-Wei Chang,
• Jinq-Chyi Lee and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2025, 21, 1671–1677, doi:10.3762/bjoc.21.131

• function. Careful manipulation of reaction conditions such as solvent and temperature is necessary to achieve sufficient diastereomeric purity in pyruvate modification. This research contributes to the development in the field of polysaccharide synthesis and draws upon established methodologies, reflecting

Synthesis of optically active folded cyclic dimers and trimers

• Ena Kumamoto,
• Kana Ogawa,
• Kazunori Okamoto and
• Yasuhiro Morisaki

Beilstein J. Org. Chem. 2025, 21, 1603–1612, doi:10.3762/bjoc.21.124

• the PL decay curves (Figure S17, Supporting Information File 1) were fitted with the single exponential function. The lifetimes (τ) were estimated to be 1.6 ns and 1.0 ns, respectively. Circular dichroism (CD) and CPL spectra of (Sp)-6 and (Sp)-7 were obtained in CHCl3 solutions (1.0 × 10−5 M), and

Thermodynamic equilibrium between locally excited and charge transfer states in perylene–phenothiazine dyads

• Issei Fukunaga,
• Shunsuke Kobashi,
• Yuki Nagai,
• Hiroki Horita,
• Hiromitsu Maeda and
• Yoichi Kobayashi

Beilstein J. Org. Chem. 2025, 21, 1577–1586, doi:10.3762/bjoc.21.121

• band follow a single-exponential decay function in all compounds (Supporting Information File 1, Figure S23 and Figure S24). As a representative example, Figure 4 presents the emission decay profiles of Pe–PTZ(TPA)2, with overlaid decay curves monitored at 600 nm and 460 nm. The lifetimes of the CT

• states were 10.7, 10.3, 9.7, and 10.8 ns for Pe–PTZ, Pe–PTZ(PTA), Pe–PTZ(PTA)2, and Pe–Ph–PTZ(PTA)2, respectively. At the probe wavelength corresponding to the LE band of the Pe moiety (460 nm), a subnanosecond decay attributable to the LE state of the Pe moiety (within the instrumental response function

• the PTZ(TPA)2 moiety and the Pe radical anion almost instantaneously. The electron transfer occurs extremely rapidly (within the instrumental response function, <100 fs), likely via a direct CT transition. Subsequently, both signals showed growth components with time constants of 2.4 and 639 ps

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• function (Scheme 4B). Furthermore, when the reaction of chromone 10 was carried out under standard conditions, the starting material was recovered unaltered, evidencing that the photocatalyzed dehalogenation step is crucial to enable the ring opening (Scheme 4C). In order to determine the role of Ni(II) in

Highly distinguishable isomeric states of a tripodal arylazopyrazole derivative on graphite through electron/hole-induced switching at ambient conditions

• Himani Malik,
• Sudha Devi,
• Debapriya Gupta,
• Ankit Kumar Gaur,
• Sugumar Venkataramani and
• Thiruvancheril G. Gopakumar

Beilstein J. Org. Chem. 2025, 21, 1496–1507, doi:10.3762/bjoc.21.112

• triggered through external stimuli to induce the switching and to modulate the function. Photo-triggerable molecular switches like azobenzene (AB) [10][11][12][13], spiropyran [14], diarylethene [15] and multifunctional AB [16] have attracted a lot of interest due to the distinct differences in the

• measurements obtained on two single FNAAP molecules. Additional I–V measurements are provided in Supporting Information File 1, section 7 for reference. Unlike the expected continuous variation of current as a function of voltage, we observed abrupt increases and decreases in the tunneling current, as

• ) are observed at both sample voltage polarities. The statistics of the number of states as a function of sample voltage are given in Figure 5b. The number of states increases as the voltage increases and reaches a maximum value of 8. We attribute the 8 distinguishable levels of current to the 8 states

Heterologous biosynthesis of cotylenol and concise synthesis of fusicoccane diterpenoids

• Ye Yuan,
• Zhenhua Guan,
• Xue-Jie Zhang,
• Nanyu Yao,
• Wenling Yuan,
• Yonghui Zhang,
• Ying Ye and
• Zheng Xiang

Beilstein J. Org. Chem. 2025, 21, 1489–1495, doi:10.3762/bjoc.21.111

• -inflammatory, antimicrobial, antiparasitic, and plant growth regulating activities. For instance, cotylenin A (1) and fusicoccin A (2) function as molecular glues to stabilize the interactions between 14-3-3 proteins and their binding partners in plant and animal cells [8][9][10][11][12]. It has been reported

Tautomerism and switching in 7-hydroxy-8-(azophenyl)quinoline and similar compounds

• Lidia Zaharieva,
• Vera Deneva,
• Fadhil S. Kamounah,
• Nikolay Vassilev,
• Ivan Angelov,
• Michael Pittelkow and
• Liudmil Antonov

Beilstein J. Org. Chem. 2025, 21, 1404–1421, doi:10.3762/bjoc.21.105

• makes possible to analyze the tautomerism in 1 as a function of (E+KE) and KK. The NMR spectra of 1 in acetonitrile-d3 are in agreement with the above analysis of tautomeric equilibration based on theoretical calculations and UV spectra. At room temperature the proton signals are very broad and

• the assignment of the carbon spectrum. The proton signal at 16.59 ppm seems to be a sum of two signals and a deconvolution with Lotenzian bandshape function was performed (Figure S5 in Supporting Information File 1). The obtained two signals have an integral intensity of 78 to 22, which is in

• corresponding state. The Franck–Condon states of the tautomers, existing in solution, are given in green. Changes of the absorbance of compound 1 at 465 nm in toluene upon turning on and off the irradiation source (365 nm). a) Change of ΔE(K-E) in kcal/mol as a function of the substitution on different

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• the system. In 2024, Liang’s group reported the replacement of N-arylacrylamides with 7-fluoro-3-homoallylquinazolin-4-ones, which are tethered to an alkenyl group at the nitrogen atom and function as radical acceptors (Scheme 17). This approach effectively facilitated photoelectrocatalytic

Enhancing chemical synthesis planning: automated quantum mechanics-based regioselectivity prediction for C–H activation with directing groups

• Julius Seumer,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2025, 21, 1171–1182, doi:10.3762/bjoc.21.94

• . The fraction of each prediction class (correct, semi-correct, wrong) as a function of the evaluation threshold is shown in Figure S1, Supporting Information File 1. Here, one can see that the number of wrong predictions is reduced by more than 30% when using an evaluation threshold of 1 kcal·mol−1

• , like meta or para functionalization. This can be done by using the workflow in the scoring function of a genetic algorithm, for example. Here, the absolute directing strength towards a specific site can be used to score different directing groups to each other and have the genetic algorithm design

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• the α-position of enamide to be an active cyclization site, with the alkyne tether acting as the nucleophile. Since it is well-established that alkynes, when activated by transition metals such as gold or platinum, can also function as electrophiles, modulating the reactivity of the decahydroquinoline

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80

Study of tribenzo[b,d,f]azepine as donor in D–A photocatalysts

• Katy Medrano-Uribe,
• Jorge Humbrías-Martín and
• Luca Dell’Amico

Beilstein J. Org. Chem. 2025, 21, 935–944, doi:10.3762/bjoc.21.76

• promising redox potentials in their excited states, indicating their potential to function as effective bimodal photocatalysts. Additionally, our photophysical characterization provided essential insights into their behavior in the excited state and stability. We initiated the study of the photocatalytic