Chemoenzymatic synthesis of the cardenolide rhodexin A and its aglycone sarmentogenin

• Fuzhen Song,
• Mengmeng Zheng,
• Dongkai Wang,
• Xudong Qu and
• Qianghui Zhou

Beilstein J. Org. Chem. 2025, 21, 2637–2644, doi:10.3762/bjoc.21.204

• overall synthetic efficiency of this route. Therefore, the development of more efficient syntheses of rhodexin A is of great significance. Recently, chemoenzymatic syntheses of steroids have made excellent progress, which can enormously shorten the synthetic routes and increase the overall efficiency [23

• -reduction of the butenolide motif. The low efficiency of this reaction prompted us to pursue an alternative two-step approach. First, we performed the deprotection to remove all the Bz groups of 16 by NH3/MeOH, furnishing the saccharide 17 in 95% yield. Eventually, the quick stereospecific C11 carbonyl

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

• [52], acetic acid [53], or solvent-free processes [54]. Ionic liquids, such as [Bu4N][OH] [55], [bmim][OH] [56], and [Et3NH][HSO4] [57], and deep eutectic solvents (DES) [58] have been introduced to improve efficiency. Traditional methods for synthesizing these compounds, however, face several

Efficient solid-phase synthesis and structural characterization of segetalins A–H, J and K

• Liangyu Liu,
• Wanqiu Lu,
• Quanping Guo and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2025, 21, 2612–2617, doi:10.3762/bjoc.21.202

• from the high cost of the specialized resin and large solvent volumes required for dilution, coupled with DPPA's poor efficiency in forming sterically hindered peptide bonds involving residues like Val or Ile. Dahiya and Kaur synthesized segetalin C (3) via a solution-phase fragment coupling strategy

• and solid-phase approaches are viable for peptide synthesis, Fmoc-based SPPS offers distinct advantages in operational simplicity and efficiency for laboratory-scale production [20]. We therefore devised a streamlined solid-phase strategy for synthesizing the Vaccaria segetalis cyclopeptide family

• sequences, coupling efficiency was significantly enhanced using a 1:1 mixture of 1-hydroxybenzotriazole (HOBt) and 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) in DMF [23]. Finally, we obtained crude linear peptides with 75% to 95% yields (Table 1). The critical head-to

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

• . Next, we evaluated the efficiency of the SG-NHCO-BU1 material in sorbing dicyanoaurate. First, we showed that SG-BU1 is stable under the experimental conditions (Supporting Information File 1, Figure S5C) and next, we investigated both materials for dicyanoaurate sorption. Thus, we gradually increased

• , exhibiting near-quantitative binding at millimolar concentrations [17]. The lower binding efficiency of BUs attached to the material compared to the free macrocycle in solution can likely be attributed to the heterogeneous nature of the solid-phase system. Moreover, the anion binding ability of BU1 may be

• [17]. The finding is also in agreement with our reported results on the noncovalent SG-BnBU system, which showed significantly higher sorption efficiency towards dicyanoaurate over dicyanoargentate [14]. We next examined the recyclability of the materials. Only SG-NHCO-BU1 was used in these

Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• and the acylazolium complex B (Ep = −0.81 V vs SCE), single-electron transfer (SET) reduction of B was thermodynamically feasible; however, the efficiency was found to be significantly low. The oxidation potential was measured to be around [Ep = +0.72 V] vs SCE, indicating that it is sufficiently

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

• enhance synthetic efficiency, reduce costs, and provide robust solutions to challenges encountered in the synthesis of complex molecular architectures. Ryania diterpenes are natural products characterized by intricate structures and high oxidation states. Biological studies have revealed that the family

• employed therein while providing an in-depth analysis of the innovation of classical methods, the application of emerging technologies, and the enhancements in synthetic efficiency achieved through multi-strategy integration. The aim is to offer readers a clear understanding of the developmental trajectory

• the simultaneous construction of four quaternary carbon centers (C1, C4, C5, and C12) and the core AB bicyclic skeleton, markedly improving synthetic efficiency. Subsequent oxidative desymmetrization of the C14–C15 olefin in (±)-33 established the sterically hindered C11 quaternary carbon center. An α

Pentacyclic aromatic heterocycles from Pd-catalyzed annulation of 1,5-diaryl-1,2,3-triazoles

• Kaylen D. Lathrum,
• Emily M. Hanneken,
• Katelyn R. Grzelak and
• James T. Fletcher

Beilstein J. Org. Chem. 2025, 21, 2524–2534, doi:10.3762/bjoc.21.194

• ring itself to also include benzophenanthridine, dibenzonaphthyridine, and benzophenanthroline heterocycles of previously unreported identity (Figure 2). In addition to studying how naphthalene, quinolone, and isoquinoline incorporation impact click and annulation efficiency, characterizing the

• isoquinoline subunits. Heterocycle subunit identity and triazole C/N connectivity influenced the annulation reaction efficiency. Aromatic π-system expansion resulting from annulation was characterized by NMR, absorption and emission spectroscopy. Five benzotriazolophenanthroline regioisomers sharing structural

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

• bilayers through the shuttling of the macrocycle carrying the ions or through a relay mechanism [10][11]. In one example, the isomerization of an azobenzene photoswitch incorporated into the axle was used to modulate the shuttling rate of the macrocycle and, consequently, the efficiency of potassium ion

Assembly strategy for thieno[3,2-b]thiophenes via a disulfide intermediate derived from 3-nitrothiophene-2,5-dicarboxylate

• Roman A. Irgashev

Beilstein J. Org. Chem. 2025, 21, 2489–2497, doi:10.3762/bjoc.21.191

• cleavage of the S–S bond and the subsequent S-alkylation reaction were successful. To suppress the side reaction and improve reduction efficiency, we next employed DMF as a polar aprotic solvent. In Table 2, entry 4, reduction of disulfide 3 in DMF at 75 °C with NaBH4 was complete within 15 min. The excess

Palladium-catalyzed regioselective C1-selective nitration of carbazoles

• Vikash Kumar,
• Jyothis Dharaniyedath,
• Aiswarya T P,
• Sk Ariyan,
• Chitrothu Venkatesh and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2025, 21, 2479–2488, doi:10.3762/bjoc.21.190

• were ineffective in improving the reaction outcome (Table 1, entry 6). Other palladium complexes promoted the formation of 2a but with diminished efficiency (Table 1, entries 7 and 8). Varying the amount of AgNO3 did also not lead to a better yield (Table 1, entry 9), and alternative nitro sources also

Synthesis of the tetracyclic skeleton of Aspidosperma alkaloids via PET-initiated cationic radical-derived interrupted [2 + 2]/retro-Mannich reaction

• Ru-Dong Liu,
• Jian-Yu Long,
• Zhi-Lin Song,
• Zhen Yang and
• Zhong-Chao Zhang

Beilstein J. Org. Chem. 2025, 21, 2470–2478, doi:10.3762/bjoc.21.189

• University, Liaoning Shenyang 110016, China 10.3762/bjoc.21.189 Abstract Natural products with topologically complex architectures are important sources in drug discovery. The pursuit of conciseness and efficiency in the total synthesis of natural products promotes continuous innovation and the development

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• . Irritation of a solution of 124 in CH3OH using a medium-pressure Hg lamp resulted in the formation of methyl ester 125 as a single diastereomer with a yield of 30%. Due to the decrease in the efficiency of this reaction at higher loads (>50 mg), the thermal conditions for the Wolff rearrangement were tested

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• all of the above criteria. For example, it can be synthesized easily and with high efficiency through the biodiesel production process, it can be reused, it is stable under storage conditions, it can be obtained from renewable resources, it is biodegradable, non-flammable etc. It is widely

An Fe(II)-catalyzed synthesis of spiro[indoline-3,2'-pyrrolidine] derivatives

• Elizaveta V. Gradova,
• Nikita A. Ozhegov,
• Roman O. Shcherbakov,
• Alexander G. Tkachenko,
• Larisa Y. Nesterova,
• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2025, 21, 2383–2388, doi:10.3762/bjoc.21.183

• desired reaction [17]. Under these conditions, the reaction was performed on a 5 mmol scale without any loss of efficiency. We next evaluated the scope of the developed protocol. The electronic and steric nature of substituents had a minimal impact on the product yields and in most cases, the desired

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

• fluorescence quenching efficiency upon iodide binding compared to the rigid WDG (KPBG/KWDG = 22.78), demonstrating its potential as a highly sensitive optical probe and offering a novel strategy for engineering dynamic supramolecular receptors. Two carbazole-based macrocyclic probes, PBG (flexible benzene ring

• cavity, which may not perfectly complement iodide's size or geometry, leading to weaker interactions and a higher-energy (less stable) complex. This energy difference aligns with the observed higher binding constant (K) of PBG, demonstrating that structural flexibility enhances anion-binding efficiency

Adaptive experimentation and optimization in organic chemistry

• Artur M. Schweidtmann and
• Philippe Schwaller

Beilstein J. Org. Chem. 2025, 21, 2367–2368, doi:10.3762/bjoc.21.180

• analyze experiments using machine learning optimization algorithms [5][6]. Together, these capabilities are dramatically increasing the speed and efficiency of chemical optimization with respect to economic and environmental objectives [7]. The contributions in this thematic issue showcase innovative

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

• experimental and theoretical studies involving these rotaxanes showed that no side reactions occur upon excitation, meaning these compounds can be operated continuously under illumination with very little efficiency loss, making them very effective photoactive units in nanodevices. In 2005, Leigh and co

• -stilbenes have 5-membered rings fused to the carbon–carbon double bond, are more photostable, and undergo reversible photoisomerization with higher efficiency (Figure 2) [75]. Notably, their cis isomer exhibits higher thermal stability than that of other commonly used photoswitches, such as azobenzene. This

• dithienylethene is in the closed form, caused by photoinduced electron transfer (PET) from the fluorescent pyrene stopper to the acceptor dithienylethene (Figure 15). Moreover, the efficiency of the PET is modulated by the macrocycle shuttling motion between the two recognition sites due to differences in

Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• efficiency and step-economy of natural product total synthesis. This symbiotic relationship has also helped to accelerate natural product biological evaluation and the subsequent biomedical development [1]. Lycopodium alkaloids are one of the largest families of natural products [2], from which famous

• and co-workers [19]. In this review article, we summarize these four total syntheses, comparatively analyze their strategic novelty and differences, and highlight the impact of enabling methodologies and concepts on the overall efficiency and economy of each total synthesis [20]. Review The Siegel

• and different approaches were developed. The Siegel synthesis harnesses the power and efficiency of two Co-mediated [2 + 2 + 2] cycloadditions to build the C2–C3’-bipyridyl moiety encoded by complanadine A. The Sarpong synthesis leverages a biomimetic approach to rapidly assemble the tetracyclic core

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

• key late-stage step in this total synthesis, the Norrish–Yang photocyclization exhibits high chemoselectivity and efficiency. It regulates selectivity through C–H bond dissociation energy and restricted bond rotation, constructing a 6/6/4 fused ring system with three contiguous quaternary carbons

• . Moreover, the reaction can be performed on a 300 mg scale, balancing selectivity, efficiency, and practicality. 1.2 Synthetic study toward phainanoids Phainanoids are highly modified triterpenoids first isolated from Phyllanthus hainanensis by Yue's group [24][25]. Biologically, these molecules exhibit

• epimers. This strategy merges photochemical selectivity with cross-coupling efficiency, avoiding reactive metal incompatibility and enabling precise stereocontrol for chiral nitrogen heterocycles. 3 Antibiotics 3.1 Synthetic study toward γ-rubromycin Since 2017, Suzuki's group has developed a

Insoluble methylene-bridged glycoluril dimers as sequestrants for dyes

• Suvenika Perera,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 2302–2314, doi:10.3762/bjoc.21.176

• structures for G2W1 and G2W3 suggest that the OMe groups fill their own cavity and thereby decrease their abilities as sequestrants. H2 achieved a removal efficiency of 94% for methylene blue whereas G2W1 demonstrated a 64% removal efficiency for methylene violet; both sequestration processes were largely

• due to its simplicity, efficiency, low cost, and the absence of hazardous byproducts [6]. Many different adsorptive materials have been investigated including activated carbon [7][8][9], hybrid nanomaterials [10], metal oxide-based hybrid materials [11], metal organic frameworks [12], polymers [13

• (Figure 2) from water. Subsequently, we present the X-ray crystal structures of G2W1 and G2W3 which helps rationalize the results from the dye sequestration experiments. Finally, we present a detailed investigation into the methylene blue removal efficiency using H2 [39] (Figure 1) and the methylene

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

• chemical oxidant or reductant [80][85], thereby reducing toxicity and waste. With these advantages, organic electrochemistry holds significant promise for improving efficiency and sustainability while enabling the development of new transformations. Meggers and co-workers developed an electrochemical

• for applications in radical chemistry. Compared with conventional batch synthesis, flow chemistry can improve efficiency and facilitate reaction scale-up [87][88][89][90]. Mechanochemistry allows reactions to be conducted with no solvent or with only a small volume of added liquid, thus providing a

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

• substrate class. Through mechanistic-guided modulation of catalysts, solvents, ligands, and angle strain, this approach achieves unprecedented reaction pathway control while demonstrating superior temporal and step efficiency compared to conventional methods. The work establishes a sustainable framework for

• transition states. This integrated control framework provides a rational basis for designing reaction conditions to optimize selectivity and efficiency in organic synthesis. In 2014, the Liu group developed an Au(I)-catalyzed cascade cyclization strategy for synthesizing polysubstituted naphthalenes using

• 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

Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives

• Loris Geminiani,
• Kathrin Junge,
• Matthias Beller and
• Jean-François Soulé

Beilstein J. Org. Chem. 2025, 21, 2234–2242, doi:10.3762/bjoc.21.170

• efficacious but face significant challenges when applied to non-symmetric systems [24], particularly in achieving regioselectivity. These methods frequently require a particular reagent pair or an excess of one reactant, which limits their efficiency and versatility. In contrast, Baeyer–Mills reactions, which

• efficiency, as the reaction proceeds smoothly even when both coupling partners possess sterically hindered substituents at the 2,6-positions. For example, the coupling of 2,6-difluorophenylhydrazine with 1-bromo-2,6-dimethoxybenzene yielded tetra-ortho-substituted azobenzene 5a in a notable yield of 63

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

• ][94]. Electrochemical transformations used renewable and clean electricity as a source of electrons and electron holes to generate radical species, showing several superiorities such as safety, economy, high selectivity, scalability, mild reaction conditions, powerful efficiency, environment-friendly

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

• impact while maintaining the efficiency of the chemical processes [1]. Green Chemistry principles outlined by Anastas and Warner in their work “Green Chemistry: Theory and Practice (2000)” [2] notably highlight atom economy, waste minimization and the use of renewable feedstock as pillars of sustainable

• ). Partial γ-acyloxy-Cy7 possesses a high fluorescence quantum yield and high photothermal conversion efficiency in PBS, two pivotal parameters in fluorescence imaging and image-guided photothermal therapy [196]. A dimerization of furfural has been found to occur at the early stage of formation of humins

• rehydration into levulinic acid (Scheme 70, route b1). It is now preferred considering raw material costs, process efficiency and market demand. Alternatively, C6 monosaccharides can also be fermented to produce pyruvic acid and acetaldehyde, which combine by an aldol reaction and lead to levulinic acid by