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

• epoxidation-triggered double cyclization reaction. In addition, the synthesis of the recently reported natural products aspera chaetominines A and B (12 and 13) [32] was addressed. Herein, we report the full accounts of these investigations, which include: 1) an improved five-step total synthesis of

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

• benzylic oxidation to generate a para-quinone methide (pQM) intermediate. Using fusarentin 6-methyl ether as an example, pQM intermediate 10 would be generated. The C10 alcohol should successively undergo an oxa-Michael addition reaction to close the THF ring, providing 7-O-demethylmonocerin. Similarly

• , monocerin and 12-hydroxymonocerin were presumably generated from their corresponding precursors through similar oxidation and oxa-Michael addition reactions. Given the fact that quinone methides served as a powerful platform for the development of rich useful organic transformations, especially, through

• , Wittig reaction with MOMPPh3Cl and LDA gave the putative methyl enol ether, which could be directly converted into 1,3-dithiane 12 with propane-1,3-dithiol. Nucleophilic addition to chiral epoxide 13 and oxidative hydrolysis of 1,3-dithiane to ketone delivered chiral β-hydroxyketone 14. Evans−Tishchenko

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

• ], norbornadiene–quadricyclane (NBD–QC) complexes [17][18][19][20][21][22][23], dihydroazulene–vinylheptadiene (DHA-VHF) systems [24][25][26][27][28][29][30], and azobenzene derivatives [31][32][33][34] (Figure 2). In addition, other reversible photoisomers exhibit potential for development as solar thermal fuels

Switchable pathways of multicomponent heterocyclizations of 5-amino-1,2,4-triazoles with salicylaldehydes and pyruvic acid

• Yana I. Sakhno,
• Oleksander V. Buravov,
• Kostyantyn Yu. Yurkov,
• Anastasia Yu. Andryushchenko,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2030–2035, doi:10.3762/bjoc.21.158

• formation of heterocyclic systems in a minimal number of steps and offer several ways to vary substituents and they are widely used in drug discovery and development, as well as in diversity-oriented synthesis [1][2][3][4]. In addition, the application of condition-based divergence strategy [5] and the

• case of aldehyde 2b, the MCR always led to the formation of a mixture of products 5d and 6d. Attempts to synthesize 5d and 6d as individual compounds under various conditions were unsuccessful. In addition, it was found that compounds 5 can be converted into oxygen-bridged heterocycles 4 after 1 hour

α-Ketoglutaric acid in Ugi reactions and Ugi/aza-Wittig tandem reactions

• Vladyslav O. Honcharov,
• Yana I. Sakhno,
• Olena H. Shvets,
• Vyacheslav E. Saraev,
• Svitlana V. Shishkina,
• Tetyana V. Shcherbakova and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2021–2029, doi:10.3762/bjoc.21.157

• [40] activities. Furthermore, a quinoxaline-containing commercial drug, caroverine, has been proven effective in the treatment of tinnitus [41]. In addition, in vivo studies in mice and rats with various quinoxalinone derivatives have shown favorable analgesic and anti-inflammatory properties as well

• with the addition of 0.1% formic acid. The use of other eluents such as acetonitrile and different ratios of hexane/ethyl acetate, dichloromethane/methanol as well as the application of methods for the isolation of triphenylphosphine oxide by complexation with calcium and magnesium salts [54][55] or

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

• they do not share a common path. Typically, in stereoselective reactions involving central chirality, the proximity between the site of reaction and the points of stereo-differentiation means that the indices [ij] are expected to have small values. In general, j = 0 in the index [ij] of an addition

• coupling of biaryls is designated as [30 20]. In addition to biaryls, axially chiral allenes are popular targets for asymmetric synthesis. Three examples of asymmetric reactions that form axially chiral allenes are shown in Scheme 4. For example, the enantioselective nucleophilic substitution to yield

• addition, the 3-step procedure is not applicable to asymmetric synthesis of interlocked molecules including mechanically planar chiral rotaxanes and catenanes, where the bond connectivity between stereogenic components is absent [40][41][42][43]. Finally, we explored the automated process for the

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

• species are limited to aryl- [7][8][10] or heteroaryl groups [7][8]. In one example methyl ethers were used [9]. Under [Pd]-catalyzed conditions a syn-type addition is observed [8][11], while [Cu] catalysts promote anti-addition [7][10]. In substrates prone to cationic rearrangements (or hydride shifts

• have been induced by addition of external halogen or selenium electrophiles and Brønsted acids. This encouraged us to develop a methodology involving a copper-catalyzed terminal alkyne arylation of propargylsilanes by diaryl-λ3-iodanes, followed by 1,2-silyl shift and terminated by nucleophile addition

• described by us recently, among other possible transformations [21][22]. Interestingly, the addition of O-nucleophiles to form 1,3-carbofunctionalization products, can only be achieved in an intramolecular fashion. In the presence of an excess (5 equiv) of external an O-nucleophile R–OX (alcohol, carboxylic

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

• ; carbonyls; NHCs; photochemistry; reduction; Introduction The introduction and exploration of N-heterocyclic carbenes (NHCs) ranks among the most important developments in chemistry research of the last 30 years [1][2][3]. In addition to their numerous valuable roles as ligands, including for important

• transformations of carbonyl substrates with umpolung processes of aldehydes such as the benzoin condensation and Stetter reaction being particularly well studied [4][5][6][7][8][9][10][11]. In these processes, addition of the NHC to the aldehyde followed by proton transfer generates the enamine-like Breslow

• intermediate A (Figure 1a), in which the formerly electrophilic carbonyl carbon reacts as a nucleophilic center. In this way, the traditional reactivity profile of the carbonyl group is transiently inverted, and unconventional product classes are generated. Alternatively, addition/elimination of the NHC to a

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

• effective tool in clinical applications [6]. However, the scarcity of metabolite 4 has prevented it from being used more widely, and thus synthesis methods for 4 are required. Compound 4 contains a cyclopentanol scaffold with stereogenicity at C8, C9, C11, and C12 (Scheme 1A). In addition, 4 is

• -deficient [28], thereby lowering the energy barrier for electrophilic radical addition. Increasing the reaction temperature to 70 °C proved detrimental, yielding only trace amounts of product 14 (Table 1, entry 5). Finally, replacing Mn(OAc)3·2H2O/Cu(OAc)2·H2O with other oxidants, such as ceric ammonium

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

• enantioenriched monoester 53 in hand, the synthesis proceeded toward fredericamycin A (60) (Scheme 9). Dione 55, which was prepared from 53 in six steps, underwent addition with alkyne 56 followed by acylation of the resulting hydroxy group with compound 57 to yield ketone 58. A subsequent seven-step

• 139, epoxide 136 was first prepared from (R)-130 in two steps. Parikh–Doering oxidation of 136 followed by addition with Et2Zn in the presence of ligand 137 afforded alcohol 138, which was subsequently converted into amine 139 via a seven-step sequence. With the fragments 135 and 139 in hand

• , ligand 205a proved to be suitable for 2-ethylpropane-1,3-diol (204). A three-step sequence then furnished enone 207, which underwent diastereoselective aldol reaction with fragment 208 to give compound 209. Alkyne 210, prepared from 209 in six steps, underwent addition with fragment 211 to yield compound

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

• a co-substrate (5 equiv; 16 μL of a 6.25 M solution in CH2Cl2) were added to glass vials in a 96-well reaction block, and the solvent left to evaporate after each addition. Subsequently, a dirhodium catalyst (1 mol %; 200 μL of a 1 mM solution in CH2Cl2) was also added to each vial. The final volume

• basis of these results, additional reactions involving the α-diazoamide substrates D4 (with a fluorosulfate warhead) and D5 (with a sulfonyltriazole warhead) were also executed. In addition to using these two α-diazoamide substrates with different warheads, two additional co-substrates bearing an alkyne

Synthesis of N-doped chiral macrocycles by regioselective palladium-catalyzed arylation

• Shuhai Qiu and
• Junzhi Liu

Beilstein J. Org. Chem. 2025, 21, 1917–1923, doi:10.3762/bjoc.21.149

• ][21][22][23]. In addition to benzene-based systems, pyridine-embedded aza[1n]metacyclophanes have been synthesized by Wang [24]. Despite these advances, N-doped chiral macrocycles incorporating extended π-conjugated moieties remain largely underexplored. To date, only a few examples, carbazole-based

• introduced. In contrast, when bulky 3,5-bis(trifluoromethyl)phenyl groups were introduced, only inherent chiral macrocyclic products (MC3) were obtained in high yield. Their molecular structures are unambiguously characterized by NMR, mass spectra and X-ray crystallographic characterization. In addition

Synthesis, biological and electrochemical evaluation of glycidyl esters of phosphorus acids as potential anticancer drugs

• Almaz A. Zagidullin,
• Emil R. Bulatov,
• Mikhail N. Khrizanforov,
• Damir R. Davletshin,
• Elvina M. Gilyazova,
• Ivan A. Strelkov and
• Vasily A. Miluykov

Beilstein J. Org. Chem. 2025, 21, 1909–1916, doi:10.3762/bjoc.21.148

• oxidation of amide and other amino acid side‐chain fragments. By tracking changes in this oxidation signal upon addition of an alkylating agent, we can infer whether the agent has effectively reacted with (and thus structurally altered) the protein. As illustrated by the black trace in the LSV plot, pure

• , the significant suppression or disappearance of the HSA oxidation peak upon addition of glycidyl esters 1–3 can be interpreted as evidence of covalent modification (alkylating) of nucleophilic sites on HSA, rather than non-specific binding or merely non-reactive association [27][28][29]. The observed

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

• 1a shows one distinct reductive peak at −1.75 V. Upon addition of one equivalent of MsOH, monoprotonated species 3a is formed, and a shift of the reduction peak to −1.92 V was observed. Subsequent addition of a second equivalent of acid leads to the formation of the bisprotonated species 4a, and as

• consequence, a shift of the reduction peak to −1.82 V was observed. However, the addition of three equivalents of methanesulfonic acid (corresponding to the typical reaction conditions) results in a decrease in the intensity of the reduction peak at −1.81 V. This observation is presumably associated with the

Preparation of spirocyclic oxindoles by cyclisation of an oxime to a nitrone and dipolar cycloaddition

• Beth L. Ritchie,
• Alexandra Longcake and
• Iain Coldham

Beilstein J. Org. Chem. 2025, 21, 1890–1896, doi:10.3762/bjoc.21.146

• aldehyde 4 could now be tested in the cascade chemistry. This entails the addition of hydroxylamine to form the oxime, followed by cyclisation (with displacement of the tosylate) to give the nitrone for the desired dipolar cycloaddition reaction. Related chemistry (without the oxindole) with a halide

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

• aza[4]helicene 8e from various aldehydes with high enantioselectivity. In addition, dienamides were found to be compatible with this method, albeit requiring a switch to CPA 3 as the optimal catalyst, which generated the 1-enamide-substituted azahelicenes 8f,g, with significant potential for diverse

• planarly chiral paracyclophanes [39]. Commenced with a macrocyclization precursor 36 featuring both a hydroxy group and an allenamide moiety, the CPA-catalyzed asymmetric intramolecular addition led to the successful construction of planarly chiral macrocycles 37 (Scheme 10). This method demonstrated broad

• . Investigations of the substrate scope revealed the compatibility of the method with various substitutions on the indole moiety and modifications to the length of the ansa chain, which produced planarly chiral macrocycles with up to 99% ee. In addition, this method was successfully employed for the catalytic

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

• increases the rate of the condensation reaction. Thus, we initially supposed that, though dodecane was only 5.6 vol % to toluene, its addition was decreasing the difference in lipophilicity between the MOF and the bulk solution, reducing the driving force to remove water from the MOF pores. When we compared

• the conversions we obtained using the dodecane calibration curve with those determined by directly comparing the integrations of the benzaldehyde and BMN protons in the 1H NMR spectra, we found little difference (Table S2, Supporting Information File 1). Thus, we decided to discontinue the addition of

• , and significantly so (ca. 10-fold) with a more appropriate comparison at the same catalyst loading of 1.5 mol% (Table 2C and D). Further, to our delight, KSU-1C14 was the most active catalyst achieving 77% conversion vs 43% for KSU-1 after 30 min. In addition, a remarkably clear and gradual increase

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

• , the synthesis can be directed towards the desired target with the use of protecting groups [41]. For the synthesis of azothiazoles 25, the addition of phenylhydrazine (22) to ammonium thiocyanate followed by ring closure and oxidation was recently proposed (Scheme 6A) [42]. Heteroarylazo-1,2,3

• of ring substitution as indigo are observed (Scheme 18) [73][74]. A complete quench of thioindigo isomerisation was obtained by the addition of OH groups in the 4-position [75]. Upon excitation of 62, it is believed a similar deactivation mechanism to the unsubstituted indigo is operative (Scheme 19

• the thermal stability from hundreds of years to a few days. The addition of a further hydrogen-bond acceptor on the stator led to the discovery of hydrazones with a thermal stability of thousands of years (Scheme 34, left) [111]. The extra H-bond in 106-E and 107-E raises the energy of the linear

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

• during GC–MS analysis) and formaldehyde (2a′′) via C–C bond scission of styrene in the presence of FeIII/O2, possibly through a 1,2-addition of O2 to styrene [49][58][59][60]. This in-situ generated aldehyde species then undergoes condensation with the amine 1a, leading to the formation of the

[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

• derivatives the reaction was accompanied by a number of side-processes, which resulted in inseparable by-products, and thus we were unable to isolate the product of the reaction of the derivative 1f. In addition, a decrease in yields was observed in the presence of a nitrophenyl group (compounds 6–8c). Other

• thiohydantoin 7, on the contrary, have a trans configuration of two vicinal stereocenters (Scheme 3 and Figure 1). Thus, in all cases we have obtained, probably, the most thermodynamically favorable isomers. This result allows us to assume a stepwise mechanism of the ylide addition to the double bond of

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

• of supramolecular interactions [33][34]. Different external stimuli, including pH changes, enzymes, light irradiation, hypoxia, and multi-stimuli responses, can alter the supramolecular structure or binding affinity to activate the opening and closing of the nano-valves. In addition to the three

• in organic solvents, [77] which is not feasible for crown ethers, CAs, and resorcinarenes. In addition, PAs can form supramolecular systems in the following ways: (1) the electron-rich cavity interacts electrostatically with cationic guests, such as methyl viologen derivatives, pyridinium salts, and

• minimal concentrations, while avoiding adverse effects throughout the body. In the future, it could be attempted to combine it with more anti-tumor drugs and apply it in clinical settings. In addition to the aforementioned SAC5A that can respond to stimuli under hypoxic conditions, they also synthesized

Unique halogen–π association detected in single crystals of C–N atropisomeric N-(2-halophenyl)quinolin-2-one derivatives and the thione analogue

• Mai Uchibori,
• Nanami Murate,
• Kanako Shima,
• Tatsunori Sakagami,
• Ko Kanehisa,
• Gary James Richards,
• Akiko Hori and
• Osamu Kitagawa

Beilstein J. Org. Chem. 2025, 21, 1748–1756, doi:10.3762/bjoc.21.138

• , ought to have different halogen bonding properties, and should be explored as different chemical entities. Meanwhile, there are very few studies on halogen bonding related to molecular chirality such as those shown in Figure 1 [27][28][29][30]. In addition, the studies on the comparison of

• poor (11% ee and 9% ee) [31]. In addition, rotational stability about the C–N bond in 1a,b was not mentioned at all. We prepared racemates rac-1a,b in accordance with Scheme 1 and separated their enantiomers [(P)-1a,b and (M)-1a,b] through medium pressure liquid chromatography (MPLC) using a semi

• racemic N-(2-bromophenyl)quinoline-2-thione, the formation of heterochiral layered polymers, in which (P)- and (M)-atropisomers were alternately connected, was detected. In addition, the heterochiral layered polymers were constructed through an n–π* interaction between the lone electron pair on the

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

• oxidation in methanol in batch electrolysis conditions, providing unsaturated esters S-3d and R-3d, respectively (Scheme 2). The previously used one-reactor two-step conditions were found to be productive for the electrosynthesis of S-3d, requiring the addition of acetic acid for the intermediate spiroketal

• of products in copper-catalyzed 1,4-addition of phenylmagnesium bromide, Giese reaction with 2-iodopropane, Simmons‒Smith or Johnson–Corey–Chaykovsky cyclopropanation, hydroboration reaction with 9-BBN, and Diels–Alders reaction with Danishevsky diene. Gratifyingly, it was found that vinyloxazoline S

• -wise process [22]. The first step involves addition of the oxazoline nitrogen to TsNCO leading to a zwitterionic intermediate A, which undergoes 1,4-conjugate addition forming a cyclic intermediate B. Subsequently, the electron-rich double bond in intermediate B reacts with a second equivalent of TsNCO

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

• the connectivities of these groups were supported from the 1H-13C HMBC spectrum. Couplings between the H8 and C9 (or H8′ and C9) atoms are consistent with the C8 and C8′ atoms linked to the carbonyl carbon (C9). In addition, couplings between the H8 and the C2, C3, C3a, and C8 carbon atoms, as well as

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

• exploiting the participation effect of the neighboring protecting group [43][44], employing anomeric lactols as acceptors is more complex as lactols with the desired configuration are frequently difficult to obtain (e.g., through anomerization). In addition to the nature of the leaving group and promoter

• addition, 2-amino-2-deoxy-1,3-diols were successfully employed as glycosyl acceptors, as exemplified by the use of GlcN-derived lactol 42, which was reacted with the 2N-Troc-protected GalN phosphite donor 47 in the presence of borinic acid catalyst to give the β,α-1,1'-linked disaccharide 48 (Scheme 4) [63

• and functional groups on glycosylation partners involved in 1,1'-bond formation can lead to unfavorable outcomes, including either the failure to form the desired 1,1'-disaccharide or the generation of multiple by-products. In addition to the stereodirecting participating protecting group on the