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

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• . We hope this review can stimulate the methodology development and application of this strategy toward further improving the synthetic efficiency of natural product synthesis. Review Total synthesis of terpenoid and alkaloid natural products through the desymmetric enantioselective reduction of five

• for the synthesis of (+)-26 to complete the first total synthesis of (+)-chamaecydin (27). The successful collective total synthesis of the two structurally complex natural products demonstrated the high efficiency of the modular synthetic strategy based on the desymmetric enantioselective reduction

• efficiency was significantly improved. Despite remarkable progress has been made, there is still a long way to go before the strategy achieves maturity for applications in natural products. Specifically, challenges remain in improving the enantioselectivity and diastereoselectivity of the desymmetric

Further elaboration of the stereodivergent approach to chaetominine-type alkaloids: synthesis of the reported structures of aspera chaetominines A and B and revised structure of aspera chaetominine B

• Jin-Fang Lü,
• Jiang-Feng Wu,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2025, 21, 2072–2081, doi:10.3762/bjoc.21.162

• confirmation of natural products is no longer a motivation for the total synthesis [1]. Nevertheless, we also witness that each year, cases continue to be reported on the total synthesis enabled revision of misassigned structures of natural products [1][2][3][4][5][6][7][8][9]. Efficiency is one of the major

• cyclization of an intermediate derived from ᴅ-tryptophan [60][61]. Subsequently, we developed a five-step total synthesis of (–)-chaetominine (1) and two diastereomers from ʟ-tryptophan [62]. Taking advantages of the high efficiency and flexibility of our strategy [60], we have synthesized several natural and

• than those using (COCl)2/DIPEA in our previous synthesis of isochaetominines [63]. We realized that employing this lactamization protocol would significantly improve the synthetic efficiency of isochaetominines 4–6. To showcase this possibility, the improved lactamization protocol was applied to

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• the synthetic steps and gain efficiency. More significantly, since the exact biosynthetic pathway of a natural product is generally very complicated and hard to elucidate clearly, a biosynthetic pathway is basically proposed by the isolating scientist according to the structural analysis of the

• synthesis probably lead this field to the lane of scientific logic, which would provide guidelines to design a bioinspired strategy. Our group has a long-time of research experience on complex natural product synthesis. To achieve higher efficiency of synthesis, we inevitably exploited the concept of

• approach. This key reaction mimics the plausible biosynthetic pathway and demonstrates great efficiency and sole diastereoselectivity, showcasing the plausibility of the biosynthetic proposal. Further redox manipulations of the last olefin and deprotection ultimately provided chabranol. To clearly confirm

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

• visible light under sunlight irradiation [59], achieving a solar efficiency of 0.4% and a solid-state isomerization efficiency of 72.7% (Figure 5b). Feng and co-workers reported the synthesis of three azopyridine polymers (ortho-, meta-, and para-) [60], with the m-azopyridine polymer exhibiting a

• development of azobenzene-based solar thermal fuels and demonstrated their potential applications. Nanocarbon-integrated azobenzene polymers: Their energy storage efficiency (up to >200%) and cycle life are primarily modulated by template confinement effects and electronic coupling. However, high costs and

• , and hinders practical deployment. Third, azobenzene groups release energy through a process involving thermal relaxation or thermally induced cis–trans isomerization. Temperature critically governs the efficiency and kinetics of this process: elevated temperatures accelerate uncontrolled instantaneous

Photochemical reduction of acylimidazolium salts

• Michael Jakob,
• Nick Bechler,
• Hassan Abdelwahab,
• Fabian Weber,
• Janos Wasternack,
• Leonardo Kleebauer,
• Jan P. Götze and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153

• changed from 440 nm (blue LEDs) to 370 nm (UV-A). This resulted in an overall improvement in the reduction efficiency with the fully reduced species 2 becoming the major product formed in 38% yield alongside the O-benzoylated species 3 (9%, Table 1, entry 5). This result is again remarkable in that it

• efficiency observed upon switching from blue to UV-A light irradiation. Nevertheless, alternative scenarios involving the potential formation of excited donor–acceptor (EDA) complexes between benzoylazolium species 1 and DIPEA were considered. Measurements of the UV–vis spectra in the presence of the amine

• products 2 or 3 limits the overall efficiency. To overcome this limitation, we considered whether a different approach could provide reduced products in yields greater than 50% relative to the starting material 1. In particular, addition of chloro(trimethyl)silane (TMSCl) to the reaction mixture could

Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization

• Miao Xiao,
• Liuyang Pu,
• Qiaoli Shang,
• Lei Zhu and
• Jun Huang

Beilstein J. Org. Chem. 2025, 21, 1964–1972, doi:10.3762/bjoc.21.152

• was treated with p-toluenesulfonic acid (p-TSA) in EtOH at room temperature to afford ketal 24 in 83% yield as a single diastereomer. Subsequently, palladium-catalyzed decarboxylative allylation delivered compound 25 in 89% yield. The efficiency of our first-generation strategy for asymmetric

• synthesis of 4 was unsatisfactory because it required nine steps to prepare bicyclic intermediate 25 with an overall yield of just 2.0%. This low efficiency prompted us to develop a more streamlined synthetic route for target compound 4. Second generation asymmetric total synthesis of tricyclic-PGDM methyl

• ester Although the efficiency of the first-generation asymmetric total synthesis strategy was limited, the development of synthetic methods during this work, particularly the transition-metal-mediated oxidative radical cyclization for stereoselective assembly of the cyclopentanol scaffold bearing the C8

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

• favored complexation, while the phenyl substitution at C4 promoted a stable coordination-bond formation. Alternatively, (S)-130 could be furnished using Cu complex 129 in the desymmetrization step with comparable efficiency (98% yield and 91% ee), and was likewise transformed into 131 in four steps

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• significant attention in this context due to its flexibility, efficiency, and practical applicability. Since the late 1980s, many research groups have investigated the use of in situ-generated low-valent titanium [20][21][22][23][24][25] and niobium [26] reagents to promote the pinacol-type coupling of imines

• sufficient ionic conductivity is crucial to achieve efficient conversion (Table 1, entry 10). Lastly, replacing tetraethylammonium tetrafluoroborate with tetrabutylammonium tetrafluoroborate resulted in a negligible reduction of the chemical efficiency (Table 1, entry 9 vs 11). As demonstrated by Shono and

• electrochemical cyclization process. In contrast, more complex and extended heterocyclic electronrich π-systems such as compound 2j was obtained in 35% yield only, presumably as a result of electronic factors affecting the efficiency of the initial radical formation [47]. To further extend the scope of this

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• Wei Liu Xiaoyu Yang Key Laboratory of Subcritical High-Efficiency Extraction, College of Chemistry and Environmental Engineering, Anyang Institute of Technology, Anyang, Henan 455000, China School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210, China 10.3762/bjoc

• interactions with the enehydrazine intermediate, which is essential for achieving high levels of stereocontrol. Using the optimal catalyst CPA 1, a series of aza[6]helicenes 3a,b was synthesized with excellent enantioselectivity and high yield. However, this method demonstrated notably reduced efficiency and

• potential in the CPA-catalyzed asymmetric synthesis of these unique chiral molecules, some current limitations and challenges still need to be addressed, particularly enhancing the efficiency of the methods and expanding the structural diversity of the products. Firstly, the chiral products generated

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

• efficiency. Keywords: metal-organic frameworks; post-synthesis modification; supramolecular catalysis; Introduction Most enzymatic reactions take place in multifunctional cavities in which multiple amino acid residues work cooperatively to orient and activate reactants [1][2][3]. These residues may also

• catalytic performance and/or systematically investigate the influence of a particular chemical or structural property on catalyst efficiency [23]. For examples of tailoring the pore environment in MOF-based catalysts to modulate catalytic performance, we can refer to the elegant work of Telfer and co

• catalysis have focused on lipophilization to prevent water-based catalyst decomposition, with only a few investigating how lipophilic pores surfaces can increase catalyst efficiency [32][33], despite enzymes employing such a strategy. The lipophilicity of enzyme active sites tends to improve reaction rates

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• be easily calculated. According to the thermal half-life, photoswitches are usually classified in P-type (thermally stable, with long half-life) and T-type (thermally unstable) [3]. The quantum yield Φ measures the efficiency of the switching, and it relates the number of photons absorbed nx to the

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• existing methodologies suffer from poor atom utilization, leading to increased waste and reduced overall efficiency, which can be challenging to manage, especially when scaling up. Building on previous studies, we envisioned a novel reaction system that facilitates the C(sp2)–C(sp2) bond cleavage of

• , FeCl3·6H2O provided the best results (Table 1, entry 2). A further reduction in catalyst loading from 25 mol % to 20 mol % and 10 mol % resulted in a noticeable decrease in both selectivity and conversion efficiency (Table 1, entries 7 and 8). This is likely due to insufficient C(sp2)–C(sp2) bond

• 6-bromo-2,4-diphenylquinoline (3g), both recognized for their antifungal activity [10], were successfully synthesized on a gram scale, showcasing the scalability and efficiency of the process (Scheme 3). After having demonstrated the broad substrate compatibility and the synthetic potential of this

[3 + 2] Cycloaddition of thioformylium methylide with various arylidene-azolones in the synthesis of 7-thia-3-azaspiro[4.4]nonan-4-ones

• Daniil I. Rudik,
• Irina V. Tiushina,
• Anatoly I. Sokolov,
• Alexander Yu. Smirnov,
• Alexander R. Romanenko,
• Alexander A. Korlyukov,
• Andrey A. Mikhaylov and
• Mikhail S. Baranov

Beilstein J. Org. Chem. 2025, 21, 1791–1798, doi:10.3762/bjoc.21.141

• ) and found that only these two abovementioned approaches are capable to perform desired cycloaddition (Supporting Information File 1, part 2). For various azolones 1–5e, these two methods demonstrated different efficiency – Table 1. Derivative 6e was formed from azolone 1e in approximately equal yield

Synthesis of chiral cyclohexane-linked bisimidazolines

• Changmeng Xi,
• Qingshan Sun and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1786–1790, doi:10.3762/bjoc.21.140

• bisimidazoline ligands 5 on the stereocontrol in catalytic asymmetric reactions (Table 1). To improve the synthetic efficiency, a different strategy for the synthesis of a nonsulfonylated cyclohexane-linked bisimidazoline with subsequent sulfonylation with different sulfonyl chlorides was also considered and

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

• cyclodextrins in terms of controllable functionalization [61]. In clinical applications, particularly for anticancer drug conjugation, CAs demonstrate remarkable cancer cell selectivity, minimized off-target effects, enhanced delivery efficiency, and reduced systemic toxicity. Additionally, their synthetic

• specific release of DOX, significantly improving the delivery efficiency and tumor targeting of hydrophobic drugs. The release of DOX from PAs also can be regulated by a pH-responsive mechanism. In 2015, Wang and coworkers synthesized a novel supramolecular prodrug nanoparticle exploiting the host–guest

• the active drug form, anthraquinone [116]. The CIA strategy effectively improves the solubility, bioavailability, and light-response efficiency of hydrophobic photo-sensitizing drugs, offering new ideas for light-controlled drug delivery systems. In 2018, Sun and colleagues designed and synthesized a

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

• presence of boron trifluoride etherate as promoter to afford the β,α-1,1'-linked disaccharide 12 in 52% yield (Scheme 2). The electron-withdrawing effect of the 2-azido group in the structurally similar donor 13 led to a significant drop in efficiency and the formation of the desired disaccharide 14 along

• , inseparable mixture of products (Scheme 7) [76]. The use of a torsional disarming 4,6-O-benzylidene acetal protecting group on both the N-phenytrifluoroacetimidate donor 81 and the lactol acceptor 82 led to a moderate improvement in glycosylation efficiency. A significant advancement was observed upon

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

• potential in advancing the green transformation of the chemical industry while enhancing inherent process safety. Safety, cost-effectiveness, and operational efficiency serve as pivotal drivers for advancing flow chemistry in nitration processes. This review provides a comprehensive analysis of the

• -flow configurations demonstrate superior safety and efficiency. While the synthetic significance of nitration is underscored by the broad utility of nitro derivatives, persistent technical challenges including regioselectivity control, over-nitration phenomena, and substrate oxidation side reactions

• , safety, and efficiency concerns, researchers have explored various types of inorganic and organic nitrating reagents to improve reaction performance through innovative chemical approaches. Patra et al. comprehensively reviewed the development and applications of organic nitrating reagents in nitration