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

• formation mechanisms of the products yielded from the methanolysis of isomeric epoxides 9, we performed a series of density functional theory (DFT) computations using the software Gaussian 16 [26]. For this, geometry optimizations and harmonic vibrational frequency computations for the structures considered

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

• enhances its therapeutic efficacy but also helps in overcoming resistance mechanisms that limit the effectiveness of other microtubule-targeting agents. Research continues to explore additional applications of 1 in various cancer types, including non-small cell lung cancer, ovarian cancer, and other soft

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

• of non-histone proteins [1], and the hydrolysis of other acyl functional groups [2]. The human genome encodes 18 histone deacetylases (HDACs), which are divided into two main groups based on their catalytic mechanisms [3]. Eleven HDACs are zinc-dependent enzymes, while the remaining seven, known as

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

• mechanisms of action have utilitarian value, as they do not account for the probability of including targets not inherent to existing drugs in their molecular mechanisms of anticancer action. The physicochemical properties of such compounds may not fit the parameters developed from databases of approved

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

• terpenoids and highlight the utility of strategically including such a step in a natural product synthesis. To start, an overview of the different classes of enzymes, and thus common mechanisms, of ring-size-altering reactions for terpenes will be presented. In Scheme 1 the four most important manifolds for

• pyrophosphate (GPP, 6). As the goal of this review is to cover mainly skeletal modifications arising from follow up biosynthetic reactions after cyclisation, only selected examples of ring-size altering fundamental steps in polyene cyclisation mechanisms will be presented now. One such example is the formation

Synthesis of diaryl phosphates using phytic acid as a phosphorus source

• Kazuya Asao,
• Seika Matsumoto,
• Haruka Mori,
• Riku Yoshimura,
• Takeshi Sasaki,
• Naoya Hirata,
• Yasuyuki Hayakawa and
• Shin-ichi Kawaguchi

Beilstein J. Org. Chem. 2026, 22, 213–223, doi:10.3762/bjoc.22.15

• different mechanisms. In addition, the DPpyP 31P NMR peak increases and decreases in conjunction with the decrease of the MPP peak and increase of the DPP peak, suggesting that DPpyP acts as an intermediate in the DPP formation process. When alcohol 1c was used (Figure 3), the reaction stopped mainly at the

Streptoquinolines A and B, new antibacterial meroterpenoids produced by Streptomyces sp. TMPU-A0679

• Akiho Yagi,
• Hitomi Tomura,
• Ami Konno and
• Ryuji Uchida

Beilstein J. Org. Chem. 2026, 22, 185–191, doi:10.3762/bjoc.22.12

• Pathogens List (BPPL) in 2024, reaffirming VRE as a “High Priority Pathogen” for which research on and the development of new antimicrobial agents are urgently needed [4]. This emphasizes the continuing demand for antibiotics with novel chemical scaffolds and mechanisms of action. In our ongoing search for

Symmetrical D–π–A–π–D indanone dyes: a new design for nonlinear optics and cyanide detection

• Ergin Keleş,
• Alberto Barsella,
• Nurgül Seferoğlu,
• Zeynel Seferoğlu and
• Burcu Aydıner

Beilstein J. Org. Chem. 2026, 22, 131–142, doi:10.3762/bjoc.22.6

• under ambient light. In addition, interaction mechanisms of dyes with cyanide were studied using the 1H NMR titration method, and it was determined that they interacted through an addition mechanism. Photophysical properties and interaction mechanisms of the compounds were also supported through density

Advances in Zr-mediated radical transformations and applications to total synthesis

• Hiroshige Ogawa and
• Hugh Nakamura

Beilstein J. Org. Chem. 2026, 22, 71–87, doi:10.3762/bjoc.22.3

• years, however, single-electron transformations mediated by zirconium complexes have begun to emerge. This review systematically highlights the groundbreaking radical mechanisms involving zirconium complexes that have been reported. Zirconium exhibits unique characteristics – such as a strong affinity

Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• Figure 7d and Figure S251d in Supporting Information File 1 provide data on the stabilization mechanism in the excited state in relation to the ICT process and the polarity of the solvent [90][91]. The graphs were generally linear, demonstrating that ICT-type mechanisms were favored for these compounds

Silica gel with covalently attached bambusuril macrocycle for dicyanoaurate sorption from water

• Michaela Šusterová and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2025, 21, 2604–2611, doi:10.3762/bjoc.21.201

• ; gold mining; macrocycles; Introduction Inorganic anions play essential roles in a variety of biological and biochemical mechanisms and are also involved in many industrial and manufacturing processes. Due to their significant environmental impact, it is important to monitor their presence and control

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• . This field serves not only as a vital tool for molecular structure validation and the discovery of new reaction mechanisms but also as a fundamental driving force behind advances in related disciplines such as pharmaceutical science. Throughout this endeavor, innovations in methods and strategies

• channels has been extensively studied, the mechanisms of action of other ryanoid diterpenoid natural products remain poorly understood. Elucidating the structure–activity relationships (SAR) of these compounds is essential for identifying the functional groups critical for their biological activity

Synthesis and characterization of a isothiouronium-calix[4]arene derivative: self-assembly and anticancer activity

• Giuseppe Granata,
• Loredana Ferreri,
• Claudia Giovanna Leotta,
• Giovanni Mario Pitari and
• Grazia Maria Letizia Consoli

Beilstein J. Org. Chem. 2025, 21, 2535–2541, doi:10.3762/bjoc.21.195

• mechanisms including elevation of reactive oxygen species (ROS) or interference with redox homeostasis, and inhibition of kinase or topoisomerase activities essential for cancer cell proliferation. The selective activity of thiouronium salts against cancer cells compared to non-malignant cells can be related

Effect of a photoswitchable rotaxane on membrane permeabilization across lipid compositions

• Udyogi N. K. Conthagamage,
• Lilia Lopez,
• Zuliah A. Abdulsalam and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2498–2512, doi:10.3762/bjoc.21.192

• azobenzene photoswitching, which is supported by MD simulations [15]. Therefore, rotaxane 1 and axle 3 permeabilize membranes through distinct mechanisms. Effect of macrocycle localization The macrocycle with the azobenzene photoswitches in rotaxane 1 can translate and be localized in either of the ammonium

• photochemical process in axle 3, and the diminished effect in rotaxane 2, indicate that release in these systems occurs through different mechanisms. Moreover, our data indicate that the localization of the macrocycle along the axle can lead to variations in release. For rotaxane 4, where the macrocycle is

Catalytic enantioselective synthesis of selenium-containing atropisomers via C–Se bond formations

• Qi-Sen Gao,
• Zheng-Wei Wei and
• Zhi-Min Chen

Beilstein J. Org. Chem. 2025, 21, 2447–2455, doi:10.3762/bjoc.21.186

• phenyl-substituted benzoisoquinoline derivatives. Two plausible reaction mechanisms were proposed in the study: one involving oxidative addition of Int 4, a five-membered rhodium cyclic intermediate, followed by reductive elimination and the other proceeding via a bimolecular nucleophilic substitution

Conformational effects on iodide binding: a comparative study of flexible and rigid carbazole macrocyclic analogs

• Guang-Wei Zhang,
• Yong Zhang,
• Le Shi,
• Chuang Gao,
• Hong-Yu Li and
• Lei Xue

Beilstein J. Org. Chem. 2025, 21, 2369–2375, doi:10.3762/bjoc.21.181

• ]. Notably, the anion-binding performance of these macrocycles is inherently governed by their conformational dynamics [9][10]. Flexible hosts adaptively adjust their cavities via induced-fit mechanisms to accommodate diverse guests, while rigid hosts rely on preorganized spatial complementarity for

• interplay between conformational selection and induced-fit mechanisms in isomeric systems remains underexplored. Cram’s preorganization theory [13] posits that prestructured hosts with minimized solvation exhibit enhanced binding stability. Recent advances [14][15][16] highlight the pivotal role of

• molecular level of the dynamic regulation mechanisms of conformations [19][20]. Although the influence of conformational dynamics on molecular recognition has been paid attention to, there is still a gap in the comparative study of flexible (PBG) and rigid (WDG) structural analogs of the same framework. In

Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• shuttling dynamics. In this review, we discuss key examples of photoswitchable rotaxanes, organized according to the position of the photoswitch, either embedded in the axle or incorporated into the macrocycle. We examine the major classes of photoswitches used, including their switching mechanisms and the

• , spirobenzopyran, stilbene and stiff-stilbene (Figure 2). Systems whose photoinduced behavior primarily depends on photoredox or energy-transfer mechanisms fall outside the scope of this review. Review Rotaxanes featuring photoswitches on the axle Rotaxanes that incorporate photoswitchable units into the axle are

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• review, drawing on examples from recently reported natural product syntheses, elaborates on reaction mechanisms, factors governing regioselectivity and stereoselectivity, and the impact of substrate structures on reaction pathways. These reactions not only serve as robust tools for the streamlined

• manipulations. Notably, under Mitsunobu conditions, 23 – with its C9 ketal remaining intact – led to 28 and 29 in 40% total yield, with a 1:2.5 ratio favoring the undesired regioisomer 29 (Scheme 5a). These two isomers arise from SN2 and SN2' mechanisms, respectively. Furthermore, when 30 (bearing a saturated

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

• trapped intermediate 152, affording alkylidenecyclopentenes 153 with high diastereoselectivity (Scheme 31, path b). By clarifying E/Z-configuration-dependent cyclization mechanisms, this work introduced the gold(I)-catalyzed 5-exo-dig cyclization of 1,3-dien-5-ynes, gaining insights into regioselective

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

• kinases” because of the lack of functional annotations and high-quality molecular probes for functional investigations [7][8]. Thus, new studies are still required for the discovery of selective inhibitors for each of these kinases in order to better clarify their mechanisms of action and their roles in

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• reaction mechanisms are disclosed if available. Keywords: alkyne; catalysis; cyclization; electrochemistry; five-membered ring; Introduction Organic five-membered rings, an essential class of organic compounds, not only are frequently used as important starting materials, intermediates or ligands in

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

Solar thermal fuels: azobenzene as a cyclic photon–heat transduction platform

• Jie Yan,
• Shaodong Sun,
• Minghao Wang and
• Si Wu

Beilstein J. Org. Chem. 2025, 21, 2036–2047, doi:10.3762/bjoc.21.159

• temperature and the Tm of the isomerized cis-azobenzene is below room temperature, while others require solvent-assisted charging mechanisms [70][71]. This structural and functional diversity makes them particularly valuable for solar thermal storage applications. Feng et al. incorporated fluorinated

Understanding the origin of stereoselectivity in the photochemical denitrogenation of 2,3-diazabicyclo[2.2.1]heptene and its derivatives with non-adiabatic molecular dynamics

• Leticia A. Gomes and
• Steven A. Lopez

Beilstein J. Org. Chem. 2025, 21, 2007–2020, doi:10.3762/bjoc.21.156

• combined with state-of-the-art multireference quantum mechanical calculations to understand the photophysical properties and mechanisms of these diazabicyclo[2.2.1]heptenes. The energetically accessible lowest excitations are nNN(σCN) → π* and range from 3.94–3.97 eV. From the >292 trajectories, the

• ][68][69][70][71][72][73][74][75][76][77][78] mechanisms of cyclic azoalkenes have been studied with experimental and computational techniques for more than six decades, in solution [51][55][59][60][61][64][67][69][70][73][74][75][76][78][79], gas phase [50][55][62][64][65], and solid state [60][63

• light source. Electronic transitions to these excited states are impossible in the experiment and thus will not be considered for this photochemical mechanistic study. DBH photodenitrogenation mechanism We then turned our attention to the photochemical reaction mechanisms leading to the formation of

Measuring the stereogenic remoteness in non-central chirality: a stereocontrol connectivity index for asymmetric reactions

• Ivan Keng Wee On,
• Yu Kun Choo,
• Sambhav Baid and
• Ye Zhu

Beilstein J. Org. Chem. 2025, 21, 1995–2006, doi:10.3762/bjoc.21.155

• reaction mechanisms. Particularly, the application to reactions that establish non-central chirality allows a numeric measurement of the stereogenic remoteness – an intrinsic property of non-central chirality reflected by the large values of the indices (i ≥ 3). We anticipate that application of the