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

• . Therefore, we decided to perform the Mukaiyama hydration on advanced intermediates. Next, a K-selectride-promoted chemo- and stereoselective reduction of the C3 carbonyl of 9 was realized to solely deliver 11 in 85% yield [33]. Then, 11 was subjected to Mukaiyama hydration conditions. Under the Fe(acac)3

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

• (H3PW12O40, HPW) as a catalyst in ethanol under microwave (μw) heating (Scheme 5) [63]. These intermediates were then subjected to the previously optimized Knoevenagel condensation conditions with rhodanine or thiazolidine-2,4-dione (Scheme 6). Notably, the hybrid compounds 9a–d, 10a–d were obtained in good

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

• carbonyl compounds and pharmaceutically relevant intermediates. Moreover, this catalytic system operates under green and sustainable conditions, tolerating a broad range of functional groups and substrate scope, and utilizes low-cost, atom-economical, non-toxic starting materials. Keywords: dual catalysis

• ; NHC; organic photocatalyst; radicals; visible-light; Introduction Over the last ten years, NHC-catalyzed visible-light-promoted radical chemistry has been extensively developed for the cost-effective and practical synthesis of bioactive intermediates, pharmaceuticals, drugs, and natural products [1

• ][2][3][4][5][6]. Recently developed photocatalysis affords sustainable, regioselective green methods for producing a wide range of functionalized carbonyl compounds and their related bioactive chiral intermediates under mild conditions, employing dual organic photoredox catalysis [7][8][9][10][11

Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• cation were consistent with earlier reports [2][26], though the configurations of the intermediates were clearly delineated. The authors proposed that dicarbonyl compound 50 serves as the key intermediate diverging to all Illicium sesquiterpenes, with a retro-Dieckmann condensation and aldol reaction

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

• alkyne difunctionalization, furyl group installation, Achmatowicz rearrangement, and subsequent functional group manipulations provided intermediates 84 and 85. C5-acylation and methylation under kinetically controlled conditions followed by Sonogashira coupling yielded cyclization precursor 89

Isoorotamide-based peptide nucleic acid nucleobases with extended linkers aimed at distal base recognition of adenosine in double helical RNA

• Grant D. Walby,
• Brandon R. Tessier,
• Tristan L. Mabee,
• Jennah M. Hoke,
• Hallie M. Bleam,
• Angelina Giglio-Tos,
• Emily E. Harding,
• Vladislavs Baskevics,
• Martins Katkevics,
• Eriks Rozners and
• James A. MacKay

Beilstein J. Org. Chem. 2025, 21, 2513–2523, doi:10.3762/bjoc.21.193

• calorimetry.c Supporting Information Supporting Information File 20: General synthetic details and procedures, characterization data for synthetic intermediates, biophysical assays, and computational details. Acknowledgements We thank Ilze Kumpina for help with the ITC data analysis. Funding This work was

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

• robust approach to a wide range of 3-substituted thiophene-2,5-dicarboxylates. These intermediates are of interest as valuable building blocks for the synthesis of more complex thiophene derivatives in both materials and medicinal chemistry contexts. The synthetic routes to 3-hydroxy-substituted TT

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

• formation of unique radical intermediates [9][10]. We previously demonstrated the Ir-catalyzed [2 + 2] cyclization/retro-Mannich reaction of a tryptamine-substituted cyclopentenone F, which led to the formation of indoline J (Figure 1b) [15]. Unlike other reported methods [16][17][18], the PET reaction of F

• TS2, the reactant (IN2), and the C19–C3 bond cleavage product IN3 wells (Figure 2c). Possible intermediates with a bicyclo[2.2.0]hexane unit located on the PES minimum were investigated by performing two-dimensional scans of simplified structures to find a minimum. When the nonbonding sp3 orbital of

• order [34][35] analyses were performed to determine the hyperconjugative interactions in the intermediates, transition states, and transient structures along the IRC path (Figure 2c and 2d). In the early stage of this process (Figure 2f, IN2 → R-50 → R-24 → TS2), formation of the C19–C3 bond arises from

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

• selenides, recognized as valuable synthetic intermediates and biologically active compounds, have been demonstrated to exhibit a broad spectrum of biological activities. Among them, the synthesis of β-(selenium)vinyl sulfones can be accomplished via selenosulfonylation reactions initiated by free radicals

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

• simple building blocks [72]. The main feature of light-induced transformations is the involvement of electronically excited states that occur during photon absorption, leading to the formation of reactive intermediates causing significant changes in chemical compound reactivity. As a result, light energy

• contraction is demonstrated by the example of converting organoborane intermediates into alcohols, amines, and E-alkenes (Scheme 32). 4 Meinwald rearrangements of epoxides The rearrangements of oxiranes annelated to cyclohexane occupy an important place in the synthesis of cyclopentanes due to the

• promotes tandem transformations with the Lewis acid, resulting in oxygen-containing bicyclic compounds 198 and 199 through the formation of oxonium intermediates E and F. In the work of Kulciţki et al. [89], a very attractive acid-induced rearrangement of homodrimanic epoxide 200 was described. This

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

• formation of the five-membered isoxazolidine ring motif, which displays a range of biologically active properties [26][27][28][29][30]. It is notable that the fused pyrrolo-isoxazolidines represent a particularly versatile class of heterocyclic compounds and intermediates, which have been demonstrated to

• scaffolds. From the standpoint of organic chemistry, it is evident that these compounds can be efficiently converted into a variety of versatile organic intermediates through the application of ring-opening reactions [49][50][51][52]. In addition to the aforementioned useful properties, the current methods

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• ; Introduction β-Lactones have attracted continuous interest and have been widely utilized as key intermediates in the synthesis of natural products and polymers due to their innate ring strain [1][2][3][4][5][6]. Moreover, several natural products and their derivatives containing β-lactone as key structural

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

• ). However, the cis isomer may undergo a 6π-electrocyclization, forming dihydrophenanthrene intermediates that further oxidize into phenanthrene derivatives, thereby irreversibly deactivating the photoswitch [75]. The first stilbene-based rotaxane was reported by Anderson and co-workers in 2001, featuring a

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

• removal of the two Boc protecting groups completed the Sarpong total synthesis of complanadine A. Efficient access of key coupling intermediates 33 and 34 further enabled Sarpong and co-workers to successfully synthesize other lycopodium alkaloids. For example, to synthesize complanadine B with mono

• enantiomers of 51 allowed Tsukano and co-workers to prepare both enantiomers of complanadine A. Their further biological evaluation of the complanadines and several synthetic intermediates revealed that the pseudo-dimeric structure, absolute configuration, and oxidation level are important for the observed

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

• -hydroxy-β-lactams or 2-hydroxycyclobutanones can function either as inherent structural motifs in target natural products or as strained reactive intermediates, facilitating C–H functionalization via four-membered ring opening [6][7][8][9][10][11]. Quinones display distinct photochemical reactivities

• generated diverse biradical intermediates via regioselective hydrogen transfer (δ-H or ε-H), further constructing various C–C bonds. This enabled efficient synthesis of the core skeletons of five natural products. The divergent strategy significantly reduces redundant synthetic steps, embodies synthetic

• (50) and D (52), respectively. Alternatively, nucleophilic addition of MeOH to 54a and 56a, followed by ring-opening elimination, arrived at the corresponding γ-keto aldehyde intermediates 72/73. Subsequent intramolecular aldol cyclization of these intermediates furnished gracilisoids C/G (51/55) and

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

• enantioenriched catalysts ranging from chiral organometallic complexes to organocatalysts (small organic molecules) have been designed, synthesized, and successfully used in several organic transformations [1][2][3]. Despite these advances, catalytic methods involving radical intermediates were very rare until

• polycyclic products in a highly diastereo- and enantioselective manner [45]. The polyene substrates were designed to facilitate a radical cyclization process, with alternating electron-poor and electron-rich olefins so as to enable polarity matching of the olefins and radical intermediates. With this design

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

• ]. Similar to “atom and step economies”, this concept emphasizes prioritizing the minimization of redox manipulations during synthesis to achieve linear and stable progression of oxidation states in intermediates. In recent years, “pot economy” and “time economy” were proposed by Hayashi, underscoring the

• components such as solvents, catalysts, ligands and so on. Unlike traditional “one-to-one” reactions, pathway-controlled “one-to-many” transformations synthesize multiple products from single intermediates, dramatically reducing preparation time and reagent requirements (Scheme 1b). As an exceptionally

• synthetic intermediates, and used to successfully modify diverse bioactive scaffolds via late-stage functionalization, collectively demonstrating the method’s synthetic utility. In 2025, the Das group developed a palladium-catalyzed cycloisomerization of 2-alkynylbenzoate-cyclohexadienone that enables

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

• variety of new tri-, tetra- and pentacyclic ring systems. The structural characterization of (E)- and (Z)-hydrazones was supported by 2D NMR techniques, while that of the target compounds by single-crystal X-ray measurements. The hydrazone intermediates and the new title compounds were subjected to a

• synthesis [18][19][20][21]. Sudhakara et al. described the advantages of using bismuth nitrate as catalyst in the synthesis of hydrazones and in the one-pot Fischer synthesis of indoles from ketones and hydrazines [22][23]. Adopting this method, hydrazone intermediates 7a–j were obtained by treatment of

• phenylhydrazone structural unit is present in several marketed drugs (herombopag [28], eltrombopag [29], levosimendan [30]) and in drug candidates that reached the human clinical trials (totrombopag [31], FP-21399 [32], sivifene [33]), hydrazone intermediates 7a–j and (E)-9a,b were also involved in the tests. The

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

• properties and wide applications. Alkynes were extensively used as starting materials or intermediates for the synthesis of five-membered rings. Recently, the electrochemical synthesis of organic five-membered rings from alkynes have been developed due to the superiorities of electrochemical transformations

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

• building block applied in the synthesis of many different substances. These are summarized in Figure 3 below [120][137][138][139][140][141][142][143][144][145][146][147]. Other furanones Several other furanones are key intermediates towards important chemicals. For example, the direct oxidation of furfural

• toward useful biobased functional compounds or intermediates with applications in fuels, polymer chemistry and fine organic synthesis (CH activation, Piancatelli rearrangement, etc.). Conversion of furfural to alcohols, aldehydes and ketones: One of the most important transformations of furfural is its

• polyamides possess unusual intrinsic luminescence and high and selective affinity towards Fe2+ and Fe3+ metal ions, which could be used as fluorescent probes in the biomedical field [195]. Heptamethine cyanine Cy7 is a very important class of intermediates in the fields of biology and photomedicine. The

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

• insertion [74] with ketone 91 and deprotection of the dithiane group delivered alleneketone 92. Sequential treatment of 92 with TsNHNH2 and NaH, the trimethylenemethane (TMM) diyl-mediated cycloaddition via intermediates 93 and 94 proceeded uneventfully to form the tetracyclic product 95. Next, reductive

• observed that the early-stage application of desymmetric enantioselective reduction could efficiently provide access to enantiomerically enriched intermediates with multiple stereocenters containing an all-carbon quaternary chiral center. Taking aforementioned advantages of this strategy, the synthetic

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

• our third-generation strategy featuring the employment of benzyl ʟ-valinate as the coupling component [63], tripeptide derivative 28 was synthesized in three steps. Exposure of 28 to DMDO in acetone followed by treating the resulting intermediates with Na2SO3 produced the proposed structure of aspera

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

• chiral allenes [15] is defined as [60] (Scheme 4A), while the desymmetrizing reactions of allenes [16] (Scheme 4B) and anthracenylidene [17] (Scheme 4C) are both classified as [54]. In the cases of Scheme 3A and 3C, the reaction intermediates (i.e., the p-quinone methide and the carbopalladation

• biphenyl ether backbone (H vs Me, highlighted in grey), which is reflected by the relatively large values of the index [74]. Although we intend to avoid reaction intermediates in the assignment of the stereocontrol connectivity index, we recognize the limitations in cases that chemical bonds are cleaved

• and restored in the course of the transformations (e.g., Scheme 4A and 4C). Such limitations become obvious in the cases of multistep, multi-intermediate reactions [32][33], particularly in the case of helical chirality where chirality transfer of intermediates is common [34][35][36][37][38][39]. In

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• stabilized allyl cation intermediates that undergo regioselective trapping by internal O- and N-nucleophiles furnishing functionalized heterocycles. This method provides access to tetrahydrofuran or pyrrolidine frameworks, each bearing a trifunctionalized (E)-configured vinyl side chain. The use of a shorter

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

• offer many synthetic advantages while the wide availability of chiral NHCs can also allow for high levels of enantioselectivity. As effective enamine and active ester derivatives, Breslow and acylazolium intermediates A and B typically react via classical two-electron polar mechanisms, however, recent

• research has demonstrated that NHCs are also capable of stabilizing radical or excited-state species [12][13]. In 2020, our group reported the concept of photo-NHC catalysis where direct excitation of acylazolium intermediates generated from o-toluoyl fluoride substrates with UV-A light resulted in a novel