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

Formal synthesis of a selective estrogen receptor modulator with tetrahydrofluorenone structure using [3 + 2 + 1] cycloaddition of yne-vinylcyclopropanes and CO

• Jing Zhang,
• Guanyu Zhang,
• Hongxi Bai and
• Zhi-Xiang Yu

Beilstein J. Org. Chem. 2025, 21, 1639–1644, doi:10.3762/bjoc.21.127

• University, Beijing, 100871, China 10.3762/bjoc.21.127 Abstract A formal synthesis of product VI with tetrahydroflurenone structure as selective estrogen receptor modulator has been realized. The Rh-catalyzed [3 + 2 + 1] reaction of yne-vinylcyclopropanes and CO (20 mmol scale, in 87% yield) for building

• the 6/5/5 skeleton, and a Heck coupling reaction constructing the [3.2.1] framework, are the two key reactions in this 11-step synthesis. Keywords: [3 + 2 + 1] cycloaddition; selective estrogen receptor modulators; synthesis; tetrahydrofluorenone; Introduction Estrogen receptors (ERs) [1][2] are

• widely distributed nuclear receptor proteins and include two subtypes, ERα [3][4] and ERβ [5][6]. These receptors can bind 17β-estradiol with similar affinity, facilitating the transfer of estrogen to various tissues in the body. Due to this, 17β-estradiol as non-selective ligand has been extensively

On the aromaticity and photophysics of 1-arylbenzo[a]imidazo[5,1,2-cd]indolizines as bicolor fluorescent molecules for barium tagging in the study of double-beta decay of ¹³⁶Xe

• Eric Iván Velazco-Cabral,
• Fernando Auria-Luna,
• Juan Molina-Canteras,
• Miguel A. Vázquez,
• Iván Rivilla and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2025, 21, 1627–1638, doi:10.3762/bjoc.21.126

• fluorescent moieties constitute promising candidates to detect Ba2+ cations [8][9] (Figure 2). Another essential component is an aza-crown ether of appropriate dimensions to capture the barium cation. In addition, one para-disubstituted phenyl (or aryl) group is installed to generate selective cation–π

• efficiency of crown ethers as components in cation-selective fluorescent probes has been extensively explored [7][30], to the best of our knowledge no previous computational DFT studies on the selectivity of crown ethers of different sizes with Ba2+ have been reported. Therefore, we explored (Scheme 2A) the

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• unique ability of these compounds to undergo selective opening of the three-membered ring at either of the two nitrogen–carbon bonds under certain conditions and to be incorporated into the target molecule as a N‒C‒C synthon is successfully used to obtain a variety of heterocyclic and acyclic nitrogen

Chemical synthesis of glycan motifs from the antitumor agent PI-88 through an orthogonal one-pot glycosylation strategy

• Shaokang Yang,
• Xingchun Sun,
• Hanyingzi Fan and
• Guozhi Xiao

Beilstein J. Org. Chem. 2025, 21, 1587–1594, doi:10.3762/bjoc.21.122

• from 15 via selective removal of the Lev group with NH2NH2·H2O successfully generated the desired pentasaccharide α-Man-(1→3)-α-Man-(1→3)-α-Man -(1→3)-α-Man-(1→2)-α-Man 17 in 83% yield in a one-pot manner, which was readily converted to the phosphorylated protected pentasaccharide 18 in 92% overall

Thermodynamic equilibrium between locally excited and charge transfer states in perylene–phenothiazine dyads

• Issei Fukunaga,
• Shunsuke Kobashi,
• Yuki Nagai,
• Hiroki Horita,
• Hiromitsu Maeda and
• Yoichi Kobayashi

Beilstein J. Org. Chem. 2025, 21, 1577–1586, doi:10.3762/bjoc.21.121

• . Notably, as will be discussed later in Figure 6d, the 1LE state of the Pe moiety can be identified by its characteristic stimulated emission in the 490–510 nm region. Based on these observations, it is concluded that selective excitation of the PTZ(TPA)2 moiety at 350 nm generates both the 1LE state of

Azide–alkyne cycloaddition (click) reaction in biomass-derived solvent Cyrene^TM under one-pot conditions

• Zoltán Medgyesi and
• László T. Mika

Beilstein J. Org. Chem. 2025, 21, 1544–1551, doi:10.3762/bjoc.21.117

• methods, the copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reaction, the so-called click reaction [7], has received substantial attention for the selective synthesis of various 1,2,3-triazoles that are of utmost importance in the synthesis of biologically active compounds such as active

• (1R,5S)-7,8-dioxabicyclo-[3.2.1]octan-2-one, CAS: 53716-82-8) or CyreneTM (Scheme 1) has received increasing interest over the last few years. It can be produced from cellulose-containing feedstocks, through pyrolysis and a selective hydrogenation of levoglucosenone (Scheme 1). Regarding the market

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• enaminones has attracted much attention over the past decades. Kuwano’s group described the synthesis of enaminones from ethyl ketones via a nickel-catalyzed selective β-amination (Scheme 1A) [31]. The preparation of enaminones can also be achieved by the reaction of aldehydes and calcium carbide in the

Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Marcin Palusiak,
• Heinz Heimgartner,
• Marta Denel-Bobrowska and
• Agnieszka B. Olejniczak

Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113

• demonstrate that the compounds exhibit selective activity towards HeLa cells. Conclusion The presented study showed that the sterically crowded thioketones 7c,d smoothly undergo the anticipated [3 + 2]-cycloaddition with diazomethane and 1,3,4-thiadiazolines 2c and 2d, respectively, were formed with complete

Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

• isonitrile remained when only 1 equivalent was employed. The limited scope of iodonium salts for arylations usually arose from the poor range of synthetically accessible symmetrical salts compared to their unsymmetrical analogues. However, the selective transfer of one of the aryl groups is a main challenge

• evaluated and their reactivity was systematically analyzed in relation to the structural features of the iodonium salts and isonitriles. The study revealed that EWG-substituted diaryliodonium salts exhibited superior performance compared to EDG-substituted ones. Furthermore, the potential for selective