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

• solid form Crystals of 1·HCl were grown from an ethanolic solution, and the crystal structure was determined by single-crystal X-ray diffraction (SCXRD, Figure 2). As seen in Figure 2a, 1·HCl adopts a twisted U shape and is involved in three hydrogen bonds. Therein, the ammonium N atom interacts with

• ). Notably, the crystal structure shows that there are no water molecules of crystallization present, nor are any other solvent molecules incorporated into the crystal packing. When comparing the diffractogram obtained by SCXRD (Figure 3, green) with that obtained by X-ray powder diffraction (XRPD) of 1·HCl

• accepted that a logD7.4 around 1–3 is desirable [14]. Thus, the observed logD7.4 of 1.59 is consistent with the high membrane permeability observed for 1. This is not necessarily to be expected based on the chemical structure of 1 due to the high intrinsic polarity of the free phenolic moiety [15]. For

Asymmetric Mannich reaction of aromatic imines with malonates in the presence of multifunctional catalysts

• Kadri Kriis,
• Harry Martõnov,
• Annette Miller,
• Mia Peterson,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2026, 22, 151–157, doi:10.3762/bjoc.22.8

• adduct in 83% ee (Table 1, entry 9). Replacing the five-membered pyrrolidine ring in the catalyst structure with the more flexible six-membered piperidine ring (catalyst H, Table 1, entry 13) reduced its selectivity slightly (78% ee). However, the catalyst derived from phenylglycine (catalyst F) or

Design and synthesis of an axially chiral platinum(II) complex and its CPL properties in PMMA matrix

• Daiki Tauchi,
• Sota Ogura,
• Misa Sakura,
• Kazunori Tsubaki and
• Masashi Hasegawa

Beilstein J. Org. Chem. 2026, 22, 143–150, doi:10.3762/bjoc.22.7

• spectroscopy, as well as high-resolution mass spectrometry (HRMS). Due to its low solubility, single crystals suitable for X-ray crystallographic analysis could not be obtained. Spectroscopic analysis and DFT calculations To elucidate the electronic structure of the platinum(II) complex, UV–vis absorption

• theory (DFT) calculations were carried out. The calculations were performed at the CAM-B3LYP/6-31G+(d,p) level, with the LANL2DZ basis set applied to the Pt atoms. The optimized structure of R-Pt is shown in Figure 2b. The dihedral angle of the binaphthyl moiety (∠C1–C2–C3–C4) was 71°, which is smaller

• calculation. (b) Optimized structure of R-Pt by DFT calculation. Emission spectrum of 1 wt % PMMA matrix (R-Pt) (λex = 300 nm). (a) CD spectra of S/R-Pt in 1.0 × 10−5 M dichloromethane solution. (b) CPL spectra of 1 wt % PMMA film (λex = 300 nm). Synthesis of the binaphthyl-based ligand and the platinum(II

Symmetrical D–π–A–π–D indanone dyes: a new design for nonlinear optics and cyanide detection

• Ergin Keleş,
• Alberto Barsella,
• Nurgül Seferoğlu,
• Zeynel Seferoğlu and
• Burcu Aydıner

Beilstein J. Org. Chem. 2026, 22, 131–142, doi:10.3762/bjoc.22.6

• colorimetric and optical changes. Because of the strong donor–acceptor structure, second-order NLO properties were studied by measuring electric field-induced second harmonic (EFISH) values, which showed significant second-order NLO responses. The experimental results were explained using density functional

• ) efficiency [14][15][16]. Indanones are highly conjugated with a planar structure, which favors overlap between the molecules. They are building blocks for many compounds, such as organic materials for optoelectronic and NLO applications [17][18]. Research shows that the absorption wavelength of the region

• * transition from the donor group to the dicyanovinyl, and longer wavelength absorption maxima are the n–π* transition of the conjugated structure [2]. Alkylamino groups (diethylamino, julolidine, and morpholine) as donor groups in chromophores have different electron-donor properties, causing a shift in the

Highly electrophilic, gem- and spiro-activated trichloromethylnitrocyclopropanes: synthesis and structure

• Ilia A. Pilipenko,
• Mikhail V. Grigoriev,
• Olga Yu. Ozerova,
• Igor A. Litvinov,
• Darya V. Spiridonova,
• Aleksander V. Vasilyev and
• Sergey V. Makarenko

Beilstein J. Org. Chem. 2026, 22, 123–130, doi:10.3762/bjoc.22.5

• biologically active properties. Thus, barbamide exhibits molluscicidal activity [7], and sintokamide A is active against prostate cancer [8] (Figure 1). As derivatives of strained and unique structure and properties [9][10] cyclopropanes are of interest for entering into various transformations along the path

• summary, we proposed a diastereoselective method for the synthesis of vicinal trichloromethylnitrocyclopropanes by forming a cyclopropane ring from a trichloromethylnitroethene substrate and an active methylene component. Variation of the methylene component structure – linear (malononitrile, methyl

• . Visualization was performed under UV light (λ 254 nm). Reagents were obtained from commercial suppliers and used without further purification unless otherwise noted. X-ray crystallography. X-ray diffraction analysis of the structure 2, 3, 9a, and 9b was performed on a Rigaku 'SuperNova, Single source at offset

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

• 53 while retaining the benzene ring structure using an iridium catalyst to selectively hydrogenate indoles and benzofurans (Scheme 7) [59]. The hydrogenated products were obtained in 90% yield with 98% ee on average. In 2024, Yin and co-workers reported an innovative palladium-catalyzed asymmetric

• was then hydrogenated to the piperidine by direct hydrogenation, and the benzene ring was then reduced to an unsaturated ketone structure by Birch reduction, completing the highly efficient total synthesis of GB13 in 6 steps with an overall yield of 10%. Total synthesis of (±)-corynoxine and

• , which perfomed as a key substrate for the aerobic oxidation. The formation of the tetracyclic 3-spirooxindole structure 137 was achieved through a transition-metal-free intramolecular cross-dehydrogenative coupling. With 137 in hand, a sequence of transformations including ketone reduction with NaBH4

Reactivity umpolung of the cycloheptatriene core in hexa(methoxycarbonyl)cycloheptatriene

• Dmitry N. Platonov,
• Alexander Yu. Belyy,
• Rinat F. Salikov,
• Kirill S. Erokhin and
• Yury V. Tomilov

Beilstein J. Org. Chem. 2026, 22, 64–70, doi:10.3762/bjoc.22.2

• isomer of anion 2 we analyzed the structure of its highest occupied molecular orbital (HOMO) and the distribution of the electrophilic Fukui function (f–) [28] – the difference in electron density between the anion and the derived radical by abstraction of one electron (Figure 2). Both approaches

• excellent yield, the structure being confirmed using single crystal X-ray analysis (CCDC 2495984). Bromination afforded a mixture of symmetric cycloheptatriene 4b and norcaradiene 6b, while intermediate cycloheptatriene 5b was not even observed. Iodination gave exclusively norcaradiene 6c. Previously

• norcaradiene product in the case of benzylation, unlike in the close analogues, is due to a steric repulsion. The structure of norcaradiene 6f was confirmed through single crystal X-ray analysis (CCDC 2495985). Allylation of anion 2 was followed by intramolecular [4 + 2]-cycloaddition in norcaradiene 6g to

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• products, depending on the type of structure of the original unsaturated starting material (Scheme 66) [207]. Similar products were obtained by Dauzonne and co-workers through the reaction of aldehydes with bromonitromethane in the presence of dimethylammonium chloride (not shown) [208]. Bonne and

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

• structure of 2c was confirmed by single-crystal X-ray analysis. The benzyl moiety was also tolerated, and the corresponding product 2e was obtained in 57% yield. 2,2-Dimethyl-5-nitro-5-nitroso-1,3-dioxane (1f) was successfully employed under the reaction conditions, leading to the formation of product 2f in

• all compounds, XRD of 2c, computational details, and copies of 1H, 13C, 14N, 1H,13C HSQC, and 1H,13C HMBC NMR spectra. Supporting Information File 5: Crystallographic information for compound 2c. Supporting Information File 6: CheckCIF report for the data of 2c. Acknowledgements Crystal structure

Total synthesis of asperdinones B, C, D, E and terezine D

• Ravi Devarajappa and
• Stephen Hanessian

Beilstein J. Org. Chem. 2025, 21, 2730–2738, doi:10.3762/bjoc.21.210

• contains a prenyl group at various positions in the indole ring [11]. The importance of the indole core structure and the nature and position of prenylation is reflected by the observation that 6-prenylindole but not 6-isopropylindole has been reported to exhibit antifungal activity [6]. Tryptophans

• metabolite and cyclic dipeptide consisting of a 7-prenylated ʟ-tryptophan and ʟ-alanine was isolated from the liquid cultures of S. teretispora containing potato broth in the medium. Its structure was based on extensive spectroscopic studies (Figure 1). Terezine D (6) exhibited modest in vitro antifungal

• activity [20]. A related metabolite lacking the C7 prenyl group had been isolated from the cultures of Aspergillus chevalieri in 1976 [21]. The structure and absolute stereochemistry were confirmed by synthesis from tryptophan and ʟ-alanine [22]. The isolation of terezine D (6) and more recently, the (3R

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

• , causes the formation of two to four diastereomers, the structure of which has been determined with 1H, 19F, 13C, 2D 1H-13C HSQC/HMBC, 1H-1H COSY/NOESY NMR and X-ray diffraction analysis. Keywords: condensed pyridones; 1,3-diamino-2-propanol; ethyl 4,4,4-trifluoroacetoacetate; methyl ketones; three

• ], fluopyram [36], and the nematicide fluazaindolisine [37] (Figure 1). The trifluoromethyl piperidine backbone is part of the structure of anticancer [38] and antirheumatic [39] agents. The fluorine-containing pyridines and their heteroannelated derivatives are known to exhibit a high biological potential, on

• functional group, the presence of which should affect their diastereomeric structure. We have found only one work describing the use of 1,3-diaminopropan-2-ol to form heterocycles, where it is reported to react with chloroacetaldehyde and carbon dioxide as an N,N-dinucleophile only, giving hexahydro[1,3

Mechanistic insights into hydroxy(tosyloxy)iodobenzene-mediated ditosyloxylation of chalcones: a DFT study

• Jai Parkash,
• Sangeeta Saini,
• Vaishali Saini,
• Omkar Bains and
• Raj Kamal

Beilstein J. Org. Chem. 2025, 21, 2703–2715, doi:10.3762/bjoc.21.208

• presented in Table 1 confirms that electron-donating groups stabilize Int1 more than electron-withdrawing groups, as expected. The electrophilic addition of [PhIOH]+ is driven by the electron-rich double bond present in the chalcone structure. Therefore, in case of chalcones with electron-withdrawing groups

• free energy profile for HTIB-mediated ditosyloxylation of chalcone with X = -NO2 leading to the formation of the α,β-ditosyloxy ketone. Free energies are reported in kcal/mol. Bond lengths are reported in Å. Structure of reactant (chalcone, compound A), geminal product (compound B), vicinal product

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

• structure 67 in 10 steps, which already represented the core veratramine skeleton, but lacked the C5–C6 double bond. For this, six more steps were needed to oxidize the C3-alcohol and install a C4–C5 double bond to arrive at enone 68. In three steps, the double bond was transposed to the correct position

• , while the right-hand fragment is an aryl bromide (D/F ring structure). Fragment A was synthesized from (S)-Wieland–Miescher ketone (34) via an eight-step sequence (Scheme 19). Fragment B was synthesized from a substituted acrylic acid in 10 steps toward aryl bromide 53. Key success factor in this

• rearranged scaffold 85 in three steps. Acetyl protection and elimination at C9–C11, followed by a Birch reduction, yielded a dienone structure. The latter was then hydrogenated, a methyl group was installed in α-position to the ketone, and an enone was formed to give 81 over 12 steps. Then, 2-ethyl-5

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

• ; Friedel–Crafts reaction; heterocycles; new ring systems; Introduction In our prior report [1] we disclosed the synthesis of new fused ring derivatives of the dibenzo[c,f][1,2]thiazepine skeleton (1, Figure 1) shown by general structure 2. In recent publications we have also reported the synthesis of new

• , respectively (Scheme 2). The structure of compounds 20e and 21g was also confirmed by single-crystal X-ray diffraction (Figure 3). We demonstrated the potential utility of the synthesized new ring systems in the field of medicinal chemistry by the synthesis of tetracyclic analogues 20b and 21b of tianeptine

• (22), an atypical antidepressant drug on the market [21][22][23][24][25], by hydrolysis of esters 20a and 21a (Scheme 3). Treatment of chloro derivative 19 with various alcohols afforded ethers 23, while its reaction with 2-(morpholin-4-yl)ethanethiol resulted in thioether 24 (Scheme 4). The structure

Chemoenzymatic synthesis of the cardenolide rhodexin A and its aglycone sarmentogenin

• Fuzhen Song,
• Mengmeng Zheng,
• Dongkai Wang,
• Xudong Qu and
• Qianghui Zhou

Beilstein J. Org. Chem. 2025, 21, 2637–2644, doi:10.3762/bjoc.21.204

• absorption and metabolism, and specific moieties like rhamnose can enhance CG potency markedly by more than 25 times [1][7]. In addition, the -OH groups on the steroids’ structure also play an important role on their activity. However, these compounds are mainly isolated from plants or animals, which not

• -electron demand Diels–Alder (IEDDA) reaction was utilized to successfully construct the BCD tricyclic structure with the correct configuration of the four contiguous stereocenters in just one step. However, the requirement of a series of protecting group manipulations undermined the step-economy and

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

• inconsistency made it challenging to rely on NMR as the primary method for confirming the structure of the expected products. To overcome this limitation, other analytical techniques, such as mass spectrometry and infrared (IR) spectroscopy, were employed. These methods successfully corroborated the formation

• tautomerization within the structure of the products, likely induced by the presence of the 4-diethylamino (4-NEt2) group, a strong electron-donating substituent. The canonical structure of thiazolidines, due to the presence of one or two carbonyl groups, thiol groups, and α-hydrogens, allows the formation of

Efficient solid-phase synthesis and structural characterization of segetalins A–H, J and K

• Liangyu Liu,
• Wanqiu Lu,
• Quanping Guo and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2025, 21, 2612–2617, doi:10.3762/bjoc.21.202

• . Secondary structure analysis by circular dichroism (CD) The secondary structures of compounds 1–10 were investigated using circular dichroism (CD) spectroscopy in aqueous buffer (0.01×PBS), deionized H₂O, and 30% TFE (2,2,2-trifluoroethanol) (Figure 2). CD spectra in the far-UV region (190–250 nm) provide

• evaluation and structure–activity relationship studies. The systematic investigation of the their key biological activities, including estrogenic activity (assessed via breast cell proliferation assays), antitumor activity (evaluated through HeLa cell inhibition assays), and antibacterial activity (evaluated

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

• . However, subsequent density functional theory (DFT) calculations by the Tantillo group on rearrangements of potential biosynthetic precursors revealed that structure 10 corresponds to a transition state rather than a stable intermediate of the 1,2-alkyl migration [27]. Their study further indicated that

• Suzuki and co-workers in 2021 [44]. Their work proposed that this core structure could be generated from a highly oxidized allo-cedrane moiety through a tandem retro-Claisen/aldol reaction. Beginning with compound 100, a 6-step sequence afforded ortho-quinone 101 (Scheme 10). Heating 101 promoted an

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

• . This field serves not only as a vital tool for molecular structure validation and the discovery of new reaction mechanisms but also as a fundamental driving force behind advances in related disciplines such as pharmaceutical science. Throughout this endeavor, innovations in methods and strategies

• intermediate, systematically deriving multiple structurally related natural products through functional group transformations and oxidation-state adjustments [3][4]. This approach efficiently constructs compound family libraries, greatly facilitating drug screening and structure–activity relationship (SAR

• the correct structure of ryanodol to be 3-epi-ryanodol (5), thereby revising the previously accepted configuration [15]. Since then, numerous analogs based on the ryanodol scaffold have been identified and characterized. As of now, 18 natural products from this family have been successfully isolated

Ni-promoted reductive cyclization cascade enables a total synthesis of (+)-aglacin B

• Si-Chen Yao,
• Jing-Si Cao,
• Jian Xiao,
• Ya-Wen Wang and
• Yu Peng

Beilstein J. Org. Chem. 2025, 21, 2548–2552, doi:10.3762/bjoc.21.197

• single crystals, and a corresponding X-ray diffraction analysis (inset in Scheme 3, selected H atoms have been omitted for clarity, and Table S3, Supporting Information File 1) unambiguously confirmed its precise structure with three continuous chiral centers. Conclusion In summary, the total synthesis

Rapid access to the core of malayamycin A by intramolecular dipolar cycloaddition

• Yilin Liu,
• Yuchen Yang,
• Chen Yang,
• Sha-Hua Huang,
• Jian Jin and
• Ran Hong

Beilstein J. Org. Chem. 2025, 21, 2542–2547, doi:10.3762/bjoc.21.196

• synthesis and structural determination of malaymycin A (1) as well as the subsequent design of structural analogues for biological evaluation [16][17][18][19][20]. Preliminary structure–activity relationship (SAR) studies revealed that fungicidal activity is highly dependent on the nature and

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

• potential to load drug molecules in the bioactive nanoassembled structure. Keywords: anticancer agent; calixarene; nanostructure; self-assembly; Introduction Cancer remains one of the leading causes of morbidity and mortality worldwide. Despite significant advancements in chemotherapy, more effective and

• ). The proton signals of the NH₂ and CH₂S groups of the isothiouronium substituents were clearly observed at 9.04 ppm and 4.23 ppm, respectively. Additionally, the carbon signal of the CH₂S group appeared at 169.3 ppm. The NMR signals, consistent with a fully symmetric structure, evidenced the exhaustive

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

• efficient binding and further underscore the complexity of these systems due to conformational and energetic preferences. Taken together with previous studies, we postulate that future nucleobases should be designed to overcome the positional challenges related to entropy and geometry. (a) Structure of a

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

• ; membrane fluidity; membrane permeability; photoswitchable rotaxane; Introduction Lipid membranes play a vital role in biology by acting as protective barriers for cells and organelles while regulating the passage of substances. Additionally, their structure and dynamics influence the activity of membrane

• organelles within the same cell [2]. Therefore, there is a great need to develop molecular tools capable of modulating membrane structure in a controlled manner, either to facilitate cargo transport (such as drug delivery) [3][4], to irreversibly disrupt membranes and induce cell death (e.g., for targeting

• spatiotemporal precision [9]. Rotaxanes have emerged as promising tools for performing various functions in lipid membranes, owing to their multiple sites for derivatization, which allow fine-tuning of their structure and function in membranes. For instance, they have been used to transport ions across lipid

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

• isolation of compounds 2 and 3 in analytically pure form allowed their structure to be established thanks to elemental analysis and HRMS. It was found that compounds 2 and 3 are dimeric derivatives of the starting thiophene, linked by sulfur bridges located at the C-3 position instead of the nitro group