Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• epoxidations of 5 are highly stereoselective [44]. Unambiguous assignment of configuration for the diastereomers was not possible on the basis of the selective 1D NOE spectra due to the lack of informative crosspeaks. Limiting the amount of oxidant (H2O2 or peracetic acid) resulted in mixtures, suggesting that

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

• selective synthesis owing to their unprecedented catalytic activity and selectivity. Advances in the field of protein engineering have made enzymatic catalysis more amenable to enantioselective organic synthesis in the past decade. Recent advances in the development of synergistic catalytic systems

• products with a new all-carbon quaternary stereocenter (Scheme 11) [86]. With a Ni(II)–bisoxazoline complex as the catalyst, various substrates underwent the transformation with good to high yields and high enantioselectivities. The reactions were regioselective, resulting in the selective

• functionalization of the terminal carbon atom of the silyl polyenolate. In the reaction of silyl tetraenol ether 47, selective reaction at the η position occurred, and the product 48 was obtained in 78% yield and 96% ee. Conclusion This perspective highlights important contributions in the area of enantioselective

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

• regulatory role in chemical transformations, exerting kinetic modulation through solvation effects on activation barriers and reaction rates, dictating thermodynamic equilibria that govern product distribution, and enabling precise reaction pathway regulation via selective stabilization of critical

• solvent-controlled selective syntheses of two polycyclic compounds (Scheme 6) [13]. Using PdCl2 as the catalyst and DMF as the solvent, substrate 22 underwent a 6-endo-dig cyclization and subsequent enone insertion, forming a palladium–carbon bond intermediate. Protonolysis yielded isocoumarin-fused

• cyclization and subsequent deprotonation furnished 1,3-disubstituted or 1,2,3-trisubstituted naphthalenes 29 (Scheme 7, path a). When the alkyne terminus was iodo-substituted or unsubstituted, the 5-exo-dig cyclization pathway proceeded via selective activation of the iodoalkyne, generating 1-methyleneindene

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

• splicing process. Among the four isoforms of CLKs, CLK3 is the one for which the biological roles are less understood, in part because no selective inhibitor of this challenging kinase has been found to date. Based on structural analysis of the CLKs we have identified the lysine 241, present only in CLK3

• 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

• that no potent and selective inhibitor of this specific kinase has been reported, to the best of our knowledge. Among the Tchem kinase inhibitors [9], only four molecules demonstrated significant enzymatic inhibition of CLK3 (from 6.5 nM to 110 nM, Table 1, [10]): SM08502, T-025, T3, and CX-4945

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

• sterically tuned substrates promotes selective N-arylation at the terminal nitrogen. The protocol tolerates a wide range of functional groups and enables the synthesis of well-decorated azobenzenes, including tetra-ortho-substituted derivatives. Notably, the reaction proceeds under an O2 atmosphere and in

• (OAc)₂/BINAP catalytic system [51], which enabled selective C–N coupling at the terminal nitrogen and suppressed denitrogenative by-products [52][53][54]. Although the general strategy is similar, our method uses the [PdCl(C3H5)]2/t-BuXPhos catalytic system, which provided higher yields and broader

• t-BuXPhos to promote selective C–N-bond formation. This approach makes use of commercially available starting materials and displays broad functional group tolerance. Notably, it enables access to sterically demanding tetra-ortho-substituted azobenzenes in moderate to good yields. The results

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

• spatial proximities obtained from either NOESY or ROESY NMR measurements. The NH moiety is close to N=CH in the (E) isomer, while NH is close to CH2 in the (Z) isomer. As an example, in case of hydrazone 7h, a selective 1D NOESY spectrum was recorded with the excitation of NH (Figure 2 and Figure 3). In

• both Figures, beside the selective 1D NOESY spectrum (upper part in Figure 2 and Figure 3), the 1H NMR spectrum (lower part) is also presented. The spatial proximity of NH with N=CH (marked with a red arrow in Figure 2) or with CH2 (red arrow in Figure 3) proves the (E) or (Z) configuration of the N=C

• ), 128.8 (2C), 126.4, 123.6, 121.2, 118.1, 116.4, 111.8, 35.0, 9.3; IR (KBr) ν̃: 3377, 1354, 1292, 1137, 1084, 694 cm−1; HREIMS (m/z): [M•]+ calcd for C17H15N3O2S, 325.0885; found, 325.0886. Phthalazinones 1, benzothiadiazine dioxides 2, and thiadiazinoindole dioxides 3. 1H NMR and selective 1D NOESY (with

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

• afforded 12a and regenerated (DMSO)nCuI. Notably, this reaction, using KI as the only additive and performing under ambient conditions in a non-volatile aqueous solvent, was a simple, selective, efficient and sustainable electrosynthesis of indole derivatives. 3-Selenylindoles were also formed by

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

•  12) [43]. Many other studies have concerned lactic acid (LA) because of its low cost and versatile reactivity owing to the presence of one hydroxy group and one carboxylic group. Zhou et al. [44] summarized the selective catalytic (chemical or biological) pathways for the conversion of lactic acid

• -synthesis of formamides and formates was achieved in particularly good yield by selective oxidation of DHA using a Cu/Al2O3 catalyst with single active CuII species at room temperature without using a base (Scheme 20). 1-Hydroxypropan-2-one Gu et al. reported the [3 + 2] cyclization reaction of 1

• such as bagasse, corncobs, stalks, switchgrass and hardwoods [156][157][158][159][160][161][162], thanks to preliminary selective dissolution and depolymerization of hemicellulose into pentose sugars. Deep eutectic solvents were recently shown to allow fractionation of lignin and production of furfural

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

• to ketone 48 via a seven-step transformation. Finally, removal of the TBS group in 48 followed by a sequential reduction and selective oxidation of allylic primary alcohol achieved the total synthesis of (−)-cyrneine A (7). The authors then moved forward to the synthesis of other target molecules

• (Scheme 3) [31][32]. Oxidation state adjustment of 48 led to the ketone 49. Starting from this common intermediate, firstly, base-promoted double bond migration and oxidation at the γ-position gave tertiary alcohol 50. Deprotection of acetyl in 50 followed by selective oxidation delivered (−)-cyrneine B

• (9). Secondly, a based-mediated concomitant double bond migration and deacetylation, and selective oxidation of allylic primary alcohol accomplished the total synthesis of (−)-glaucopine C (10). On the other hand, Barton–McCombie deoxygenation and isopropylation of 43 produced ketone 52. Subsequently

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

• synthesis of (–)-isochaetominine A was increased from 25.4% to 30.8% over five steps. Secondly, a new protocol featuring the use of an aged solution of K2CO3/MeOH to quench the DMDO epoxidation-triggered cascade reaction was developed, which allowed the in situ selective mono- or double epimerization at C11

• aspera chaetominine B. Keywords: epoxidation; selective epimerization; stereodivergent synthesis; structural revision; tandem reaction; Introduction In contemporary organic chemistry, due to the widespread application of modern separation and analytical techniques, the structural elucidation and

Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design

• Daniil V. Khabarov,
• Valeria A. Litvinova,
• Lyubov G. Dezhenkova,
• Dmitry N. Kaluzhny,
• Alexander S. Tikhomirov and
• Andrey E. Shchekotikhin

Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161

• indolo[1,2-c]quinazoline derivatives was patented as anti-HCV compounds acting through selective inhibition of viral polymerase (Figure 1, top) [17]. Other notable bioactive indoloquinazoline compounds include the natural alkaloids tryptanthrin and hinckdentine A (Figure 1, bottom). Tryptanthrin (indolo

• reports that focused on natural alkaloids or limited antimicrobial studies, this study expands the pharmacological scope by demonstrating selective antiproliferative effects and identifying promising SAR trends. The originality of the research lies in linking strategic scaffold functionalization

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

• unreacted, which released the secondary alcohol, followed by BCl3-promoted selective cleavage of the isopropyl and one methyl protection ultimately furnished thenatural product fusarentin 6-methyl ether. With fusarentin 6-methyl ether in hand, we explored the bioinspired oxidation/oxa-Michael addition. This

• transformation was successfully achieved by using PhI(OAc)2 as oxidant, providing 7-O-demethylmonocerin, containing the cis-substituted THF ring with sole diastereoselectivity. Site-selective mono-methylation gave rise to monocerin. The bioinspired approach successfully found applications in the total synthesis

• process, which further supported the probability of the proposed biosynthetic approach. Subsequently, site-selective methylation on phenol provided 24, which further underwent O-directed demethylation to afford (12S)-hydroxymonocerin. On the other hand, a two-step protocol involving Mitsunobu reaction

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

• -selective cross-metathesis, respectively [9]. In general, racemic cyclopentanol precursors (A ring system, prepared in 6–9 steps) have been used to form the polyfunctionalized tricyclic frameworks incorporating contiguous stereocenters. In previous syntheses, the efficient construction of the cyclopentanol

• 4 was expected to be derived from tricyclic substrate 26 via a Z-selective cross-metathesis [9]. The allyl group in compound 26 could be installed in β-keto ester 21 via sequential transesterification [33] and palladium-catalyzed decarboxylative allylation [32]. The regio- and diastereoselective

• stereochemistry at C9. Therefore, alcohol 32 was subjected to a one-pot Mitsunobu reaction, hydrolyzation, and spirolactonization to give the corresponding alcohol 26 with inversed configuration at C9. Finally, terminal alkene 26 was transformed by Dai’s Ru-catalyzed Z-selective cross-metathesis with 33 [9][40

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

• selective reaction at one of the symmetrical functional groups in the precursor, thereby breaking the symmetry and establishing a chiral center. Meanwhile, since the site where the reaction occurs is distant from the newly formed stereocenter, this strategy offers unique advantages, especially in the

• (+)-dehydrovoachalotine was prepared by a selective oxidative cyclization of a 1,3-diol moiety (Scheme 30) [74]. Treatment of the known prochiral diol 246 with DDQ first oxidized the benzylic C6 position to give intermediate 247, followed by intramolecular attack of the hydroxy group to construct the tetrahydrofuran ring

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

• differences in IC50 values reflected the degree of alkylating potency and the selective toxicity toward cancer cells. Conclusion In this study, we synthesized and comprehensively characterized a series of glycidyl esters of phosphorus acids 1–3, evaluating their structural features, cytotoxic potential, and

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

• for accessing chiral compounds. Starting from racemic starting materials, this method entails selective conversion of one enantiomer facilitated by a chiral catalyst, yielding enantioenriched products and allowing for the recovery of unreacted substrate with a high level of enantiopurity [24][25

• para-selective C–H amination reaction with dibenzyl azodicarboxylate (0.8 equiv) resulted in efficient kinetic resolution, which yielded both the C–H amination product 69 and recovered (+)-68 with high enantioselectivity (see 68a–c, Scheme 19). Moreover, this method was also applicable to the kinetic

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

• groups. This selective functionalization yielded MOFs in which the catalytically active amines are confined within highly lipophilic pores, reminiscent of many enzyme active sites. We determined that systematically increasing the lipophilicity of the pores results in a commensurate increase of catalyst

• whose pores are uniformly decorated with different lipophilic groups (Figure 2A). Using this strategy, we quantitatively functionalized the –OH groups of KSU-1 with isopropyl and tert-butyl isocyanate. While primary isocyanates were less selective, starting to react at the amines before the hydroxy

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

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

• -metal catalysts. One of the key transformations in organic synthesis is the selective oxidative cleavage of alkenes to yield ketones or aldehydes [43][44][45][46][47]. Traditionally, such transformations have been achieved using various oxidizing agents, transition-metal-based systems, organo- and

• hypothesis, we commenced our investigation by employing arylamine 1a and styrene (2a) as model substrates. The optimized reaction conditions are presented in Table 1. Building upon our previous studies, where we investigated how solvent selection can influence the selective formation of quinoline scaffolds

[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

• fluoride, is used for the synthesis of spirocyclic derivatives from arylidene-azolones. Four types of the corresponding heterocycles have been studied. A series of 7-thia-3-azaspiro[4.4]nonan-4-ones was obtained with yields varying from 17 to 99%. The stereochemical study revealed selective formation 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

• , ease of modification, electron-rich and hydrophobic cavities, and highly selective molecular recognition. In recent years, numerous supramolecular drug delivery systems utilizing aromatic macrocycles have been developed. This review article provides an overview of the advancements of controlled drug

• release systems based on host–guest selective recognition, self-assembly, and nano-valves by the use of of calixarenes and pillararenes from five perspectives: pH, light, enzyme, hypoxia, and multi-stimuli combination responses. Furthermore, the article projects the future clinical application prospects

• chiral CA named chiral azo-calix[4]arene derivative (FC4AD) (Figure 10) [117]. Its interaction with enantiomers of aminoindanol in solution was investigated. It was found that FC4AD has high selective binding and release for (1R,2S)-1-amino-2-indanol, forming a 1:1 complex. S-phenethylamine was used as 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

• feature asymmetrically distributed functional groups across their two pyranose rings, emphasizes the importance of robust, stereoselective synthetic strategies capable of producing fully orthogonally protected 1,1′-linked sugars suitable for selective chemical modification. This review highlights recent

• ]. Diarylborinic acids have been shown to provide exclusive catalytic performance in the site-selective monofunctionalization of various 1,2- and 1,3-diols [60], as well as in the regioselective glycosylation of polyhydroxyglycosyl acceptors via base-promoted deprotonation of a specific hydroxy group involved in

• , the chemical synthesis of thiotrehalose analogs [116][117] provides a versatile tool for the construction of therapeutically relevant ligands or inhibitors of carbohydrate-specific innate immune receptors. Synthetic thiodigalactosides and their derivatives have been identified as selective inhibitors

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

• reactions up to 2021, and summarized the characteristics of the main organic nitrating reagents discussed in their work [6]. Yang et al. developed 5-methyl-1,3-dinitro-1H-pyrazoleas a controllable nitronium ion source for mild, selective (hetero)arene nitration. This method achieves condition-controlled

• selective mono- or di-nitration and facilitates late-stage C–H nitration of biorelevant molecules, with DFT/mechanistic studies revealing synergistic 'nitro effect' and 'methyl effect' underlying the reactivity [7]. Jia et al. developed dinitro-5,5-dimethylhydantoin (DNDMH) as an efficient arene nitration

• phenomenological nature limits their utility for fundamental process understanding despite providing practical optimization guidance under constrained conditions. The Kulkarni group [35][36] established a kinetics model for the nitration reaction in synthesizing the selective herbicide pendimethalin using

Influence of the cation in hypophosphite-mediated catalyst-free reductive amination

• Natalia Lebedeva,
• Fedor Kliuev,
• Olesya Zvereva,
• Klim Biriukov,
• Evgeniya Podyacheva,
• Maria Godovikova,
• Oleg I. Afanasyev and
• Denis Chusov

Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130

• halogen atom transfer (XAT) agent [17][18]. Standard reduction potentials illustrate that hypophosphite is a powerful four-electron reductant [19]. Our previous studies have proved that NaH2PO2 can be a selective reducing agent in the catalyst-free reductive amination process [20][21][22] that can impart

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• identified. While the employment of L9 afforded endo-selective [3 + 2] cycloadducts 60, using Trost ligand L10 resulted in a complete reversal to the exo-cycloadducts 61. DFT calculations were performed and indicated that these two ligands act in different ways in the cyclization process, providing