Improved synthesis and physicochemical characterization of the selective serotonin 2A receptor agonist 25CN-NBOH

• Adrian G. Rossebø,
• Hannah G. Kolberg,
• Anders E. Tønder,
• Louise Kjaerulff,
• Poul Erik Hansen,
• Karla A. Frydenvang,
• Jesper Østergaard and
• Jesper L. Kristensen

Beilstein J. Org. Chem. 2026, 22, 175–184, doi:10.3762/bjoc.22.11

• , oxygen atoms red, and chloride ion green. b) The crystal packing reveals alternating layers, a polar layer with hydrogen bonds (black dashed lines), and a hydrophobic layer with π–π-stacking (grey dashed lines). SCXRD and XRPD spectra of different preparations of 1·HCl. Blue: SCXRD spectrum of 1·HCl. Red

Circumventing Mukaiyama oxidation: selective S–O bond formation via sulfenamide–alcohol coupling

• Guoling Huang,
• Huarui Zhu,
• Shuting Zhou,
• Wanlin Zheng,
• Fangpeng Liang,
• Zhibo Zhao,
• Yifei Chen and
• Xunbo Lu

Beilstein J. Org. Chem. 2026, 22, 158–166, doi:10.3762/bjoc.22.9

• its multiple oxidation states and ability to form diverse bonds with carbon, nitrogen, and oxygen. This versatility underpins the pivotal roles of organosulfur compounds in pharmaceuticals, catalysis, and materials science [1][2][3][4]. Among these, sulfilimines (R2S=NR') have attracted growing

• interest due to their unique reactivity and value as intermediates in molecular design and medicinal chemistry [5][6][7][8][9][10] (Figure 1). In contrast, sulfinimidate esters, which feature a tetravalent sulfur–oxygen (S(=N)–O) motif, remain a relatively underexplored subclass of organosulfur compounds

Total synthesis of natural products based on hydrogenation of aromatic rings

• Haoxiang Wu and
• Xiangbing Qi

Beilstein J. Org. Chem. 2026, 22, 88–122, doi:10.3762/bjoc.22.4

• catalytic hydrogenation are relatively rare. This is partly due to the high stability of six-membered aromatic heterocycles, such as pyridine, making it difficult to interrupt the aromaticity under mild conditions [34]. Furthermore, the heteroatoms (such as nitrogen and oxygen atoms) within the saturated

• oxygen atoms from the substrate and the metal catalyst, which fixed the conformation of the polycyclic scaffold. As a result, the top face is sterically less favored, thereby hydrogen approaches from the opposite face. The subsequent addition of another two equivalents of hydrogen also supported this

Advances in Zr-mediated radical transformations and applications to total synthesis

• Hiroshige Ogawa and
• Hugh Nakamura

Beilstein J. Org. Chem. 2026, 22, 71–87, doi:10.3762/bjoc.22.3

• alkyl radicals to afford compound 25 as a major product [16][17][18][19][20]. In contrast, this study revealed that the strong affinity of zirconium for oxygen reverses this trend, leading instead to compound 24 as a predominant product. The generality of the reaction was demonstrated with a variety of

• zirconocene catalysts using substrates 23l–n. In both cases, the regioselectivity was found to be reversed. With titanocene, the reaction proceeds through the more stable, substituted radical, whereas with zirconocene, the high oxygen affinity of zirconium is the key factor driving the opposite

• strong affinity of zirconium for oxygen atoms [4][21]. Building on this concept, they envisioned that a similar reaction system could be applied to the homolytic cleavage of C–O bonds in alcohols and ethers. When benzyl alcohol and ether derivatives 49 were treated with zirconocene in the presence of a

One-pot synthesis of ethylmaltol from maltol

• Immanuel Plangger,
• Marcel Jenny,
• Gregor Plangger and
• Thomas Magauer

Beilstein J. Org. Chem. 2025, 21, 2755–2760, doi:10.3762/bjoc.21.212

• through fermentation, or a synthetic intermediate derived thereof is being utilized. For example, the 1969 Pfizer patent describes the oxidation of kojic acid (3) with molecular oxygen to comenic acid, which is then decarboxylated to yield pyromeconic acid. An aldol addition with acetaldehyde followed by

Sustainable electrochemical synthesis of aliphatic nitro-NNO-azoxy compounds employing ammonium dinitramide and their in vitro evaluation as potential nitric oxide donors and fungicides

• Alexander S. Budnikov,
• Nikita E. Leonov,
• Michael S. Klenov,
• Andrey A. Kulikov,
• Igor B. Krylov,
• Timofey A. Kudryashev,
• Aleksandr M. Churakov,
• Alexander O. Terent’ev and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2025, 21, 2739–2754, doi:10.3762/bjoc.21.211

• overcome existing constraints in functional group compatibility, efficiency, and reagent scope. In this regard, the direct formation of nitrogen-nitrogen or nitrogen-oxygen bonds presents a significant challenge due to the variety of possible side processes and the low thermodynamic driving force for N–N

Competitive cyclization of ethyl trifluoroacetoacetate and methyl ketones with 1,3-diamino-2-propanol into hydrogenated oxazolo- and pyrimido-condensed pyridones

• Svetlana O. Kushch,
• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess,
• Pavel A. Slepukhin,
• Alexandrina S. Volobueva,
• Vladimir V. Zarubaev and
• Victor I. Saloutin

Beilstein J. Org. Chem. 2025, 21, 2716–2729, doi:10.3762/bjoc.21.209

• conformation, with a deviation of the oxygen atoms O(1) by 0.5 Å for 5ctc and nitrogen atoms N(1) by 0.4 Å for 5ctt. In trans-junction, bicycles 4att, 4atc (Figure 2c,d) have a flattened fixed skeleton with a dihedral angle of 24.8–27.3° (see Table S9, in Supporting Information File 1), in which the

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

Synthesis of new tetra- and pentacyclic, methylenedioxy- and ethylenedioxy-substituted derivatives of the dibenzo[c,f][1,2]thiazepine ring system

• Gábor Berecz,
• András Dancsó,
• Mária Tóthné Lauritz,
• Loránd Kiss,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2645–2656, doi:10.3762/bjoc.21.205

• ring systems containing a two or three-carbon linker between the nitrogen atom of the thiazepine ring and the nitrogen (3), oxygen (4), or sulfur (5) atom linked to the C(11) atom [2][3]. In continuation of our efforts to study new ring systems, we decided to synthesize new tetra- and pentacyclic

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

• aldehyde 1, activated by protonation of the oxygen atom through structure ii, forming the intermediate aldol iii. In the presence of EDDA, water elimination occurs in intermediate iv, yielding the Knoevenagel adducts 3 or 4. Synthesis of novel imidazo[1,2-a]pyridine–thiazolidinone hybrids To further

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

• /organophotocatalyzed oxidative Smiles rearrangement of O-aryl aldehydes 26 has been developed using oxygen as the terminal oxidant under visible-light dual catalysis. This approach afforded highly functionalized 2-hydroxyarylbenzoates 27, tolerating electron-deficient and electron-rich substituents. The C–O bond

• cleavage and the new C–O bond formation process were achieved using NHC (10 mol %), a photocatalyst (2 mol %), and DABCO (1.5 equiv), providing the corresponding aryl salicylates 27 in moderate to good yields. Mechanistic studies support the oxidation of the Breslow intermediate by oxygen in the presence

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

• embellished by additional bridging via a γ-lactone and a γ-lactol ring, resulting in a caged pentacyclic scaffold with a 5/5/5/5/5 ring arrangement. The compound demonstrates neuroprotective activity by mitigating oxygen-glucose deprivation-induced cell injury in SH-SY5Y cells. Since its isolation in 2017

• neuroprotective effects against oxygen-glucose deprivation-induced cell injury in SH-SY5Y cells, suggesting its potential as a lead compound for the treatment of neurodegenerative diseases. The possible biosynthetic pathway of illisimonin A was also proposed by Yu and co-workers, as illustrated in Scheme 1. The

• deprotection of the cyclization precursor was essential, as the TES-protected analogue of 35 failed to deliver the desired spirocycle 38 under the Nazarov cyclization conditions. α-Oxidation of 38 with molecular oxygen afforded 39, which was then converted to 40 via formation of a chloromethyl silyl ether

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

• stereocenters characteristic of the target molecule, the authors strategically implemented this methodology. This approach efficiently established two carbon–carbon and four carbon–oxygen bonds while introducing four contiguous stereocenters, successfully assembling the highly functionalized AB ring system

Synthesis and characterization of a isothiouronium-calix[4]arene derivative: self-assembly and anticancer activity

• Giuseppe Granata,
• Loredana Ferreri,
• Claudia Giovanna Leotta,
• Giovanni Mario Pitari and
• Grazia Maria Letizia Consoli

Beilstein J. Org. Chem. 2025, 21, 2535–2541, doi:10.3762/bjoc.21.195

• mechanisms including elevation of reactive oxygen species (ROS) or interference with redox homeostasis, and inhibition of kinase or topoisomerase activities essential for cancer cell proliferation. The selective activity of thiouronium salts against cancer cells compared to non-malignant cells can be related

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

• linker are highlighted in red. Sequences for RNA hairpins and PNA ligands used for binding studies. Major-groove view of hydrogen-bonding interactions in the (A) Db1*U–A triplet, (B) Db2*U–A triplet, (C) Db2*C–G triplet, and (D) Db3*U–A triplet. Carbon, hydrogen, oxygen, and nitrogen are labelled in

Effect of a photoswitchable rotaxane on membrane permeabilization across lipid compositions

• Udyogi N. K. Conthagamage,
• Lilia Lopez,
• Zuliah A. Abdulsalam and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2498–2512, doi:10.3762/bjoc.21.192

• include local membrane heating through non-radiative decay of axle 3, disruption of lipid packing via photolysis of axle 3, or the formation of reactive oxygen species (ROS) that may react with the unsaturated acyl chains of EYPC lipids; DPPC, by contrast, lacks double bonds. Further studies will be

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

• notable DNA intercalation and antiproliferative effects [16][17], while TT–BODIPY derivatives were shown to efficiently generate singlet oxygen and demonstrate light-induced cytotoxicity, highlighting their promise as photodynamic therapeutic agents [18]. Near-infrared TT–DPP-based dyes have also been

The intramolecular stabilizing effects of O-benzoyl substituents as a driving force of the acid-promoted pyranoside-into-furanoside rearrangement

• Alexey G. Gerbst,
• Sofya P. Nikogosova,
• Darya A. Rastrepaeva,
• Dmitry A. Argunov,
• Vadim B. Krylov and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2025, 21, 2456–2464, doi:10.3762/bjoc.21.187

• rings. The internal C–C–C angles in them differ leading to more freedom for the side substituents in furanosides. This, in our opinion, means that the π–π interactions between the phenyl rings must increase in this case. However, a repulsive interaction that occurs between O-1 and O-2 oxygen atoms in

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

• 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

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

• generate singlet oxygen (¹O2), which can be controlled through dithienylethene photoisomerization. Therefore, the authors investigated these nanoparticles for bioimaging and apoptosis of HeLa cells. When the dithienylethene is in the open form, the nanoparticles have relatively high cytotoxicity due to the

• form selective hydrogen bonds between the carbonyl oxygen of the fumaramide unit and the N–H groups of benzylic amide rings. Upon isomerization to the cis isomer, the hydrogen-bonding interactions are weakened, enabling the macrocycle to migrate to a second recognition station [61]. Despite their

• . Figure 7 was adapted with permission from [16], Copyright 2023 American Chemical Society. This content is not subject to CC BY 4.0. Dithienylethene-based [1]rotaxane shuttling motion triggered by pH changes (top). Dithienylethene photoswitch modulates singlet oxygen generation to kill HeLa cells (bottom

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

• [20]. This compound significantly elevates reactive oxygen species levels in murine peritoneal macrophages (73 ± 12%) and exhibits potential as a lead for developing immunomodulatory agents. In 2021, Yang’s group reported a concise enantioselective total synthesis of (+)-cyclobutastellettolide B

• 56a (Scheme 9) – formed via [4 + 2] cycloaddition of singlet oxygen with the southern furan moiety in gracilisoid F (54) and gracilisoid H (56), respectively – served as branching points in the downstream divergent synthesis. Kornblum–DeLaMare-type rearrangement of 54a and 56a assembled gracilisoids B

• bonds of 83 (Scheme 10). Building block 76 was first obtained in 18% overall yield from β-ketoester 74 through a sequence involving Michael addition, decarboxylation, nitrile hydration, and cyclization under vacuum. Aminoketal 81 – a direct precursor to the oxygen-sensitive α,β-unsaturated iminium 81a

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

•  2, path b). In the following years, Liu and co-workers discovered that the protonation of intermediate 2 triggered its conversion to intermediate 3, which subsequently underwent oxidation with oxygen, resulting in the generation of an indenone skeleton 6 [9]. This tunability achieved efficient and

• intermediate 40 when using substrates with unsubstituted nitrogen. Concurrent oxygen-involved cyclization then furnished indeno[1,2-c]quinoline 41 (Scheme 9, path b). This work established a pathway-controlled strategy for efficient access to benzo[a]carbazole and indeno[1,2-c]quinoline derivatives. In 2019

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

• closed vial in which the reaction is carried out does not contain the necessary amount of oxygen. Structure determination of the products was also supported by single-crystal X-ray diffraction in the case of several representatives: 3b, 3d, 3e, 3g, 3h, (E)-7a, 7b, 7d, 7e, (E)-7f, (Z)-7h, 7i, and (E)-9a

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

• level of oxygen content in biomass, small molecules arising from biomass often possess a carbonyl group. This is why biobased platform molecules possessing a carbonyl group, either under the form of an aldehyde, a ketone, an acid or an ester, play a dominant role in biobased chemistry. This review aims

• co-workers developed an electrocatalytic strategy for the synthesis of HFO from furfural [111]. The very important and key bioactive compound HFO was formed by using water as an oxygen source and chalcogenides such as CuS, ZnS, or PbS as electrocatalysts. CuS nanosheets gave the best performance

• Griesbeck reported the tetraphenylporphin-photosensitized oxygenations of furan and derivatives in non-polar aprotic solvents, yielding the corresponding monomeric unsaturated secondary ozonides through a (4 + 2) cycloaddition of singlet oxygen onto the diene linkage of the furan ring. The attack of a

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

• =C6 double bond to afford triacetate 60 as a single diastereoisomer. Base-promoted hydrolysis and concomitant oxidation under oxygen atmosphere gave vicinal diketone 61. Finally, the introduction of mono-bromo and di-bromo atoms achieved the total synthesis of (−)-hamigeran B (11) and (−)-4