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

• -well flat-bottom plates at a density of 5 × 103 cells per well and allowed to adhere for 24 hours under standard culture conditions. Preparation of compound solutions. Stock solutions of diglycidyl methylphosphonate (1), diglycidyl methylphosphate (2), and triglycidyl phosphate (3) were prepared by

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

• applications in the preparation of chiral ligands. Keywords: chiral piperazines; electrosynthesis; flow chemistry; green chemistry; imino-pinacol coupling; Introduction Vicinal diamines represent a highly valuable class of compounds that, over the past decades, have found widespread application in natural

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

• ; nitrogen – blue; carbon – grey; hydrogen – pale green). Proposed synthetic approach. Preparation of the aldehyde 4. Cycloaddition with N-methylmaleimide. Cycloaddition with N-phenylmaleimide. Cycloaddition with dimethyl fumarate and dimethyl maleate. Supporting Information Supporting Information File 30

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

• preparation. Before introducing the different photoswitch classes in this review, we familiarise ourselves with different photophysical properties. A photochromic molecule can switch reversibly between a stable and a metastable state, which are shown in an energetic profile as two local minima (Figure 1

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

• electron pair on the bromine atom and a π* orbital of the quinoline-thione ring, rather than a π-type halogen bonding. Although we attempted the preparation of single crystals of the optically pure form of 2a, unfortunately, crystals suitable for X-ray measurement could not be obtained (2a is chemically

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

• competent substrate for the aza-Diels–Alder reaction in with TsNCO to give oxazolo[3,2-c]pyrimidine derivative 7 as a single diastereomer. Proposed approach for the preparation of vinyloxazoline 6. Synthesis of furfuryl amino alcohols S-2d and R-2d and their electrochemical oxidation to esters S-3d and R-3d

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

• -protected malassezione, which upon deprotection yields malassezione in an overall yield of ca. 20%. This is an improvement over the preparation of the isonitrile followed by an Fe hydride initiated isonitrile–olefin intramolecular coupling reaction, which generated malassezione with an overall yield of ca

• [20], or, more recently, (iii) prepared via an Fe hydride initiated isonitrile–olefin intramolecular coupling reaction (Scheme 1A) [18]. The reported synthetic route relies on an initial 4-step preparation of the isonitrile precursor, which was accomplished in an overall yield of ca. 14%. The

• subsequent iron-catalyzed reaction afforded 1 in only 35% yield. To avoid the low-yielding preparation of the isonitrile, we elected to use commercially available indole-3-acetic acid as the starting material, and to utilize an approach similar to that described for the synthesis of dibenzylketones from the

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

• review includes only the most relevant and recent developments in the preparation of α,α-linked 1,1'-glycosides. The review places particular emphasis on the synthesis of unsymmetrical trehalose derivatives, both with respect to the nature of the monosaccharide components (Glc, Gal, Man, GlcN, GalN, etc

• approach for the preparation of TMS-protected α-lactol acceptors was employed in the synthesis of a series of partially desymmetrized 1,1'-α,α-linked disaccharides (Scheme 13). 6-O-TBDPS-protected TMS-α-glucoside 161 was coupled with thioglycoside donor 160, furnishing the α,α-1,1'-disaccharide 162 with

• groups, particularly with regard to their type and positioning on the monosaccharide units. Other protocols allow for the preparation of highly desymmetrized 1,1'-disaccharides, albeit sometimes at the expense of only moderate isolated yields. Achieving stereoselectivity on the lactol acceptor side

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

• ], insertion reactions [16][17][18], cycloaddition reactions (e.g., [4 + 1], [3 + 2]) [19][20], and others [21][22][23]. Particularly, isocyanides have been widely exploited toward the preparation of centrally chiral structures through transition-metal-catalyzed or organocatalytic asymmetric reactions [24][25

• substrates under the standard conditions (Scheme 4b). On one hand, such findings demonstrated that the second cyclization determines enantioselectivity; on the other hand, it provided a practical way to the preparation of unsymmetrical pyrido[6]helicenes 26. Isocyanide-based multicomponent reactions Except

• chiral catalyst. Central-to-axial chirality transfer In parallel with Zhu’s work, Du, Chen, and co-workers reported an alternative way for the preparation of axially chiral 3-arylpyrroles [41] through a catalytic asymmetric Barton–Zard reaction [42] via central-to-axial chirality transfer strategy [43

Transition-state aromaticity and its relationship with reactivity in pericyclic reactions

• Israel Fernández

Beilstein J. Org. Chem. 2025, 21, 1613–1626, doi:10.3762/bjoc.21.125

• to the preparation of triazaphospholes and triazaarsoles, π-conjugated species with potential applications in materials science due to their luminescent properties [98]. However, these heavier alkyne analogues are typically kinetically unstable, which limits their use as dipolarophiles. Despite that

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

• reagents for the preparation of 3-aryl-substituted benzo[4,5]thieno[3,2-b]pyrroles by the annulation of the 1H-pyrrole ring to the benzo[b]thiophene system (Scheme 1, reaction 6). The behavior of indoles as aza-analogs of the benzo[b]thiophenes under the identified catalytic annulation conditions is also

Facile synthesis of hydantoin/1,2,4-oxadiazoline spiro-compounds via 1,3-dipolar cycloaddition of nitrile oxides to 5-iminohydantoins

• Juliana V. Petrova,
• Varvara T. Tkachenko,
• Victor A. Tafeenko,
• Anna S. Pestretsova,
• Vadim S. Pokrovsky,
• Maxim E. Kukushkin and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 1552–1560, doi:10.3762/bjoc.21.118

• examples of oxindole/1,2,4-oxadiazole [20] and hydantoin/1,2,4-triazoline [22] spiro-compounds. Synthesis of dipolarophiles (5-iminohydantoins 2a–i). Preparation of the dipole precursors 4a–d. 32CA reactions of nitrile oxides with 5-iminohydantoins (synthesis of spiro-compounds 5a–l). Isolated yields are

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

• further the applicability of the present synthetic method. Due to the excellent solvating power of CyreneTM, the “one-pot” synthesis of 1,2,3-triazoles could be proposed to eliminate the preparation and isolation steps of azide components. This could open an even greener and facile protocol for CuAAC

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

• act as both electrophiles and nucleophiles [7]. This makes enaminones very reactive, providing an excellent scaffold for organic synthesis. Thus, enaminones are valuable building blocks in the preparation of several carbocyclic [8][9][10][11], heterocyclic [12][13][14][15][16][17][18] as well as

• 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

• ]-cycloaddition of respective thiocarbonyl dipolarophiles (preferably non-enolizable thioketones) with diazomethane, was demonstrated as a favorable method for their generation [5][6]. In the past three decades, 1,3-dipoles 1 have extensively been studied as useful building blocks for the preparation of various

• (for synthesis of 4b,c, and 4e, see ref. [15]). The solution of diazomethane (CH2N2) in pentane was prepared without distillation and determination of the concentration following a procedure described in an earlier publication [28]. Preparation of 2c as a new precursor of thiocarbonyl S-methanide 1c

• . Witczak (Wilkes University) for stimulating discussions in the course of preparation of the manuscript. Funding Financial support by the University of Łódź within the IDUB grant (2023-2024) is acknowledged (G.M.). The authors (A. O. and M. D.-B.) thank the Polish Ministry of Science and Higher Education

Highly distinguishable isomeric states of a tripodal arylazopyrazole derivative on graphite through electron/hole-induced switching at ambient conditions

• Himani Malik,
• Sudha Devi,
• Debapriya Gupta,
• Ankit Kumar Gaur,
• Sugumar Venkataramani and
• Thiruvancheril G. Gopakumar

Beilstein J. Org. Chem. 2025, 21, 1496–1507, doi:10.3762/bjoc.21.112

• experimental conditions. The choice of molecules that can be studied under ultra-high vacuum (UHV) is limited due to the requirement of their thermal stability and UHV compatible sublimation temperature. Therefore, the solution-based preparation method and solid-state measurements at ambient conditions hold

• accommodate ≈200 Tbits in a 1 cm2 area. Experimental Preparation of adlayer The FNAAP molecule is synthesized as per our previous report [29]. Ultra-thin films were prepared by drop casting from ethanolic solutions of molecules (concentration between 10−5 to 10−6 M) on freshly cleaved highly oriented

Heterologous biosynthesis of cotylenol and concise synthesis of fusicoccane diterpenoids

• Ye Yuan,
• Zhenhua Guan,
• Xue-Jie Zhang,
• Nanyu Yao,
• Wenling Yuan,
• Yonghui Zhang,
• Ying Ye and
• Zheng Xiang

Beilstein J. Org. Chem. 2025, 21, 1489–1495, doi:10.3762/bjoc.21.111

• diterpenoids, including alterbrassicicene E and brassicicenes A and R in 4 or 5 chemical steps from brassicicene I. This strategy lays the foundation for the preparation of fusicoccane diterpenoids and their analogues for biological studies. Keywords: cotylenol; fusicoccane diterpenoids; heterologous

• chemical steps. This work lays the foundation for the preparation of fusicoccane natural products and exploration of their biological activities. Selected fusicoccane diterpenoids and overview of this study. (a) Representative members of the fusicoccane diterpenoid family. (b) This work: heterologous

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

• bioactive compounds. According to the DrugBank there are more than 250 approved drugs classified as amides [2]. Just recently, between February 2021 and June 2022, sixteen anticancer drugs containing an amide bond have been approved by the U.S. FDA [3]. Consequently, the preparation of amides has garnered

• low tolerance to sensitive functional groups. Due to these reasons, alternative routes toward the preparation of amides are still in great demand in modern synthetic chemistry [5]. The arylation of isonitriles was introduced nearly a decade ago as an alternative synthetic pathway for the preparation

• . Control experiments, Figure S20). Conclusion In conclusion, a novel synthetic methodology for the preparation of benzamides from isonitriles and diaryliodonium salts has been proposed utilizing visible-light photoredox ruthenium-based catalysis. Both symmetrical and unsymmetrical diaryliodonium salts were

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• by Son and co-workers illustrates recent advancements in the use of dioxazolones in synthetic transformations with copper salts [4]. The authors remark that these catalytic systems, which employ dioxazolones as electrophilic amide sources, were applied for the preparation of diverse amidated products

• , who focus on the preparation of phenethylamines and phenylisopropylamines via reduction of substituted β-nitrostyrenes using a system of sodium borohydride and copper(II) chloride [9]. The transformations are performed in one pot and proceed under mild conditions. The β-nitrostyrene products could be

Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper

• Andrei Paraschiv,
• Valentina Maruzzo,
• Filippo Pettazzi,
• Stefano Magliocco,
• Paolo Inaudi,
• Daria Brambilla,
• Gloria Berlier,
• Giancarlo Cravotto and
• Katia Martina

Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108

• anti-inflammatory activity [8]. Moreover, they can be applied in disorders of the central nervous system, such as insomnia and Alzheimer’s disease [9][10]. The preparation of 2-aminobenzoxazoles classically proceeds via cyclocondensation reactions from pre-functionalised precursors, or via the C2

• efficiency. In the context of the C2 amination of azoles, to the best of our knowledge, only a few studies [48][50] have explored this approach, suggesting significant opportunities for further development and improvement. Building on our previous experience in the preparation and characterisation of

• in the preparation (theoretical loading). This suggests that optimum catalyst distribution and activity is achieved with 5 wt % supported CuCl. The two catalysts were also characterised by FTIR and DR UV–vis spectroscopy, to obtain information about the grafted aminopropyl ligand and inserted copper

Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles

• Vladimir G. Ilkin,
• Pavel S. Silaichev,
• Valeriy O. Filimonov,
• Tetyana V. Beryozkina,
• Margarita D. Likhacheva,
• Pavel A. Slepukhin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104

• Chemistry for Metals and Molecules, Department of Chemistry, KU Leuven, Celestijnenlaan 200F, Leuven B-3001, Belgium 10.3762/bjoc.21.104 Abstract A one-step method has been developed for the preparation of 2,3-dihydro-2-sulfonyl-3,4,5-substituted 1,2-thiazoles by the reaction of acryl thioamides and

• was synthesized. Experimental Thioamides 1a,f,g,l,r [19], 1b,c,d,e,j,u,x [20] and iodonium salts 2a [21] and 2f [22] were synthesized according to the previously described methods. The structures of all thioamides used in this study are provided in Supporting Information File 1. Preparation of

• precipitate was filtered off and washed with cold ethanol and diethyl ether. Preparation of 2-sulfonyl-2,3-dihydro-1,2-thiazoles 3 (general procedure). Method A. The corresponding thioamide 1 (1.0 equiv) and DCM (1 mL) was added to an oven-dried standard microwave vial with a volume of 10 mL. The resulting

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• hydrostatic pressure (HHP) was found to be an efficient activation method in several catalyst- and solvent-free reactions and has found application for the syntheses of heterocycles and the preparation of active pharmaceutical ingredients (APIs) via acylation and acid- and solvent-free esterification. The

• ][33][34][35], especially in the realm of high pressure chemistry [36][37], in the present work we demonstrate a variety of new, catalyst- and additional solvent-free applications of HHP to develop green synthesis methods. Here, we describe several cyclization reactions for the preparation of a variety

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• is to provide a comprehensive review of oxetanes in terms of their preparation and synthetic utility. Because multiple reviews of similar formats covering literature up to late 2015 have already been published [12][32][33][34], we will discuss primarily the most recent advancements since the year

• intramolecular E2 elimination. Finally, the importance and power of the intramolecular Williamson etherification has also been demonstrated by the kilogram-scale synthesis of oxetane intermediate 41, which is a key intermediate in the preparation of the previously mentioned IDO1 inhibitor 2 (Scheme 9) [16

• a preparation of oxetanes via silicon-directed electrophilic cyclisation of homoallylic alcohols 49 (Scheme 12) [46]. The reaction was promoted by a bromonium cation and moderate to high yields of oxetanes 50 were obtained. The authors claim the reaction was diastereospecific for disubstituted

A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones

• Ashutosh Nath,
• John Mark Awad and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92

• R1 residue on the furan ring was found to have the most significant impact on the IMDA reaction. A bromine atom at the 3- or the 4-position resulted in products 8a–i in 66–86% yields, while a bromine atom or a methyl group at the 5-position inhibited the IMDA reaction in the preparation of 8j and 8k

• thiophene to reduce the diene's reactivity or altering the electrophilicity of the dienophile. Based on the computational analysis of the transition states, reaction mechanisms for the IMDA and the dehydration re-aromatization process are proposed in Scheme 5. In the IMDA reaction for the preparation of

• group on the imidazopyridine moiety have direct electronic impact on the IMDA reaction. This integrated reaction process provided a new avenue for the preparation of heterocyclic scaffolds with potential biological activity. Experimental General procedure for the synthesis of intermediates 4 and 6 The

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• ) attached to the allyl precursor 114. Iteration of this process required ozonolysis of 113, followed by its conversion to an organometallic intermediate 116, which was then reacted with allyl 114 to yield another deoxypropionate product, 117. The synthesis began with the preparation of the precursor chiral

• undesired oxidation to the corresponding phosphane oxide. The work continued with the preparation of the chiral organometallic reagent 124. Starting from known bromide 122, which was readily accessible from Roche ester (R)-121 [52] or 1,3-diol 123 [53][54] through literature procedures, the Grignard reagent

• applications in medicinal chemistry. Chemical structure of borrelidin (1). Synthetic strategy for Morken’s C2–C12 intermediate 20 as reported by Uguen et al. [41]. Preparation of monoacetates 37 and ent-38 by Uguen et al. [41]. Preparation of sulfones 27 and ent-27 by Uguen et al. [41]. Attempts to couple