Melifoliox B, a novel phloroglucin derivative isolated from Melicope barbigera (Rutaceae) and synthesis of new oxidation products from melifoliones A and B

• Horst Weber,
• Kim-Thao Tran-Cong,
• Bernhard Mayer,
• Guido J. Reiss,
• Iryna S. Konovalova,
• Marc S. Appelhans,
• Kenneth R. Wood and
• Claus M. Passreiter

Beilstein J. Org. Chem. 2026, 22, 535–546, doi:10.3762/bjoc.22.39

• could be identified as iodized phenyl ether of melifolione A (10), based on its HRESIMS and 1H NMR spectrum. The quinols 3 or 4 could not be detected. Phenols with additional electronegative substituents (e.g., nitro or acetyl) and at least one ortho-positioned hydrogen atom initially react with

Get a better glimpse on sequential photoreactions of trisnorbornadienes with ¹⁹F NMR spectroscopy

• Julian Felix Maria Hebborn,
• Ben Eric Merten,
• Thomas Paululat and
• Heiko Ihmels

Beilstein J. Org. Chem. 2026, 22, 527–534, doi:10.3762/bjoc.22.38

• useful complementary tool [38][39][40][41]. Firstly, the 19F nucleus is only slightly less sensitive for NMR spectroscopy than the 1H nucleus [42]. Additionally, fluoro substituents may be attached such that they will give well-separated signals in less complex spectra, thus allowing conclusive and

• ortho-fluoro substituents. These substituents also induce a strong electron-withdrawing effect on the chromophore and thus lower the HOMO energy, likely leading to a larger HOMO–LUMO gap and to a small hypsochromic shift of the absorption (1f: λmax = 273 nm; parent norbornadiene 1b: λmax = 283 nm) [49

• hindrance induced by the fluoro substituents in the ortho positions [54]. It should be noted that there is only very limited data available to compare the effect of the substitution pattern on the half-life of aryl-substituted norbornadienes to support this interpretation [55]. However, the effect of ortho

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• macrocycle. Hence, this pathway enables the quick assembly of multiple derivatives. The late-stage allene-Prins reaction also facilitates the application of other substituents on the central 3-methylenetetrahydropyran unit. On top of that, the commonly used NHK reaction involving a Cr(II)-catalyst is

A facile and practical method for the synthesis of trans-(±)-taxifolin and its derivatives via Darzens reaction

• Bo Peng,
• Panpan Yang,
• Maaz Khan,
• Xiaotong Lin,
• Jiang Wu,
• Peng Fu and
• Qingqing Wu

Beilstein J. Org. Chem. 2026, 22, 443–450, doi:10.3762/bjoc.22.31

• expanded synthesis of taxifolin derivatives with oxidant-sensitive substituents. Results and Discussion 2,4,6-Trihydroxyacetophenone was used as starting material, and its hydroxy groups were protected as methoxymethyl (MOM) ether by treatment with MOMBr (6.0 equiv) in the presence of NaH (4.0 equiv) to

• . The stereochemical outcome of the Darzens reaction may produce the α,β-epoxycarbonyl products with either the substituents on the same side or opposite side of the epoxy functionality, i.e., as cis/trans isomers. In this work, the α,β-epoxycarbonyl product contains bulky multiple-substituted benzene

• moieties (such as bis- or tris-MOMO-substituted phenyl substituents). Due to the steric hindrance, the trans-configured product with the phenyl substituents on the opposite side of the epoxy functionality is obtained. Additionally, the clean reaction process shown by TLC and the NMR spectrum of the product

Synthesis and stereochemical analysis of dynamic planar chiral oxa[7]orthocyclophene

• Yukiho Hashimoto,
• Yuuya Kawasaki,
• Kazunobu Igawa and
• Katsuhiko Tomooka

Beilstein J. Org. Chem. 2026, 22, 436–442, doi:10.3762/bjoc.22.30

• on the differences of the heteroatom and substituents on the (E)-alkene moiety [11][12]. The half-lives of the optical activity optt1/2 of 1aa (X = O, Y = H) and 1ba (X = NTs, Y = H) were 380 h and 56.7 h at 25 °C, respectively, indicating that the stereochemical stability of the oxygen-containing

Synthesis and anti-cancer activity of naphthalimide–organylselanyl conjugates

• Rajkumar Ravi and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2026, 22, 416–435, doi:10.3762/bjoc.22.29

• secondary amino functions strongly suppress acetylation and the embedded sulfur function contributes to the apoptosis induction [40][41].The third modification route centres on functional group engineering, in which small amine substituents are replaced with polyamines or long aliphatic chains, thereby

• into the naphthalimide framework. These differences highlight the distinct electronic environments introduced by the aryl and octyl selenium substituents. The 77Se NMR spectral data provide further confirmation. Compound 7 exhibited a 77Se NMR resonance peak at 393 ppm, while compound 8 showed a more

Cone p-aminocalix[4]arenes enriched with ‘clickable’ alkyne or azide functionalities

• Ilia Korniltsev,
• Vasily Bazhenov,
• Alexander Gorbunov,
• Dmitry Cheshkov,
• Stanislav Bezzubov,
• Vladimir Kovalev and
• Ivan Vatsouro

Beilstein J. Org. Chem. 2026, 22, 399–415, doi:10.3762/bjoc.22.28

• or a trialkylammonium cation inside the joint cavity formed by two cone calix[4]arene macrocycles [46][47][48][49][50][51][52][53][54]. This phenomenon has been thoroughly investigated, including the effects from substituents in the urea groups and/or at the calixarene narrow rim upon the

• calixarene aromatic units in comparison with the ipso-nitration of the corresponding tert-butylated ones. Even larger amounts of side products were formed, thus confirming the involvement of the tightly arranged narrow-rim substituents in calixarene 6 and 7 in undesired side processes under nitration

• propargyl groups at their narrow rims. The formation of the partially nitrated calix[4]arenes 12–14 and 16 as major reaction products described above was quite unexpected, and these compounds were not used further in this study which was more concerned with calix[4]arenes having four equal substituents at

Dialkylaminoalkylation of β-ketosulfones via ring-opening of 3-sulfonylpyrrolidines

• Evgeny M. Buev,
• Alexander V. Pavlushin,
• Vladimir S. Moshkin and
• Vyacheslav Y. Sosnovskikh

Beilstein J. Org. Chem. 2026, 22, 383–389, doi:10.3762/bjoc.22.26

•  1). Altering the substituents at the sulfonyl group made no significant impact on the yield of the reaction. An application of β-ethoxycarbonylsulfone lowered the yield of the pyrrolidine 2f (53%), apparently due to the lower acidity and activity of its methylene group, however, increasing the

• , that allows a broad functionalization of the 3-(sulfonyl)butan-1-amine with various substituents and their utilization as building blocks. We believe this approach has promising features for further development and pharmaceutical applications. Valuable amino sulfonic acids and aminosulfones. Selected

Recent advances in the cleavage of non-activated amides

• Eun-Sol Choi and
• Hyo-Jun Lee

Beilstein J. Org. Chem. 2026, 22, 352–369, doi:10.3762/bjoc.22.23

• substituents on the nitrogen (e.g., tosyl, carbamate, or acyl groups) distorts the planarity of the amide and diminishes amidic conjugation (Scheme 1b). These “twisted” amides exhibit a dramatically enhanced electrophilicity at the carbonyl carbon and a significantly weaker C–N bond strength [28][29][30][31

• electron-donating and electron-withdrawing substituents, and alkylamides having primary, secondary, and tertiary alkyl moieties at the α-position, were also suitable substrates, producing the corresponding amides 122–131 in high yields via successful generation of the acyl iodide intermediates 121

• aniline furnishing acetylanilide 158 in 87% yield. A wide range of arylamines bearing electron-donating or electron-withdrawing substituents, as well as heteroarylamines, were also competent nucleophiles, delivering the corresponding amides 159–161 in good yields. EPR studies suggested a single-electron

Spirobarbiturates with a pyrrolizidine moiety: synthesis, structure and biological evaluation

• Arthur A. Puzyrkov,
• Andrew S. Drachuk,
• Ekaterina A. Popova,
• Alexander V. Stepakov and
• Vitali M. Boitsov

Beilstein J. Org. Chem. 2026, 22, 274–288, doi:10.3762/bjoc.22.20

• 10.3762/bjoc.22.20 Abstract Polycyclic spirobarbiturates containing a pyrrolizidine moiety were synthesized via a one-pot three-component 1,3-dipolar cycloaddition reaction of alloxan, ʟ-proline and N-substituted maleimides. The reaction stereoselectivity was found to depend on the nature of substituents

• alloxan and α-amino acids) reacted with N-methylmaleimide was published by Ronald Grigg’s group in 1994 (Scheme 3) [52]. The authors reported the synthesis of spirobarbiturates containing various substituents: R’ = iPr (67%), Bn (61%), and Ph (66%). In this work, which is a continuation of studies on the

• provided in Supporting Information File 1. Notably, for compounds 4a and 4b containing non-aromatic substituents in the succinimide moiety, the signals of protons CH4 and CH6 overlap, whereas no such overlap occurs with aromatic substituents. The assignments of the methine proton signals for all compounds

Arene activation via π-bond localization: concepts and opportunities

• Paul Meiners,
• Julian J. Melder and
• Tobias Morack

Beilstein J. Org. Chem. 2026, 22, 257–273, doi:10.3762/bjoc.22.19

• aromatic π-system. Such binding imparts a conjugated diene character onto the uncoordinated portion of the arene (Figure 8A). In contrast to the earlier reaction modes, the aromatic system lacks substituents or other pre-existing functionalities that would steer its reactivity. The hydrogenation of η2

• sulfone complex of W(0) (Scheme 3A) [60]. As established previously [61], protonation of η2-arene ligands bearing electron-withdrawing substituents generates reactive arenium intermediates that react with nucleophiles to furnish disubstituted η2-cyclohexadiene complexes. A second protonation/nucleophilic

A mild and atom-efficient four-component cascade strategy for the construction of biologically relevant 4-hydroxyquinolin-2(1H)-one derivatives

• Dmitrii A. Grishin,
• Kseniia I. Sharkovskaia,
• Ilya G. Kolmakov,
• Daria A. Ipatova,
• Rostislav A. Petrov,
• Nikolai D. Dagaev,
• Dmitry A. Skvortsov,
• Maria G. Khrenova,
• Valeriy V. Andreychev,
• Sergei A. Evteev,
• Yan A. Ivanenkov,
• Roman L. Antipin,
• Olga А. Dontsova and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2026, 22, 244–256, doi:10.3762/bjoc.22.18

• activity [33]. Halogen substituents in this position have been shown to modulate antibacterial, antiviral, and antiproliferative activities, likely through electronic effects and improved target binding. The C3 position was functionalized with a propanoic acid moiety, explored in both its open-chain (acid

• , is likely due to the electronic effects within pyranoquinoline. As an enol ester conjugated with an amide and an aromatic ring, electron-withdrawing groups decrease electron density on the enol OH, while aliphatic substituents (methyl, ethyl) increase electron density on the alcohol oxygen. This

Conformational analysis of difluoromethylornithine: factors influencing its gas-phase and bioactive conformations

• Matheus P. Freitas

Beilstein J. Org. Chem. 2026, 22, 237–243, doi:10.3762/bjoc.22.17

• exploring conformational effects associated with the difluoromethyl (–CHF₂) motif. The presence of vicinal fluorine substituents is known to strongly influence conformational equilibria through stereoelectronic effects, notably the fluorine gauche effect [7]. This effect arises from hyperconjugative

• complex. Elucidating this interplay is essential for rationalizing DFMO’s inhibitory potency and may also offer broader insight into how fluorinated substituents control molecular conformation in biologically relevant environments. Although the biological milieu is known to induce only minor structural

Screwing the helical chirality through terminal peri-functionalization

• Devesh Chandra,
• Sachin and
• Upendra Sharma

Beilstein J. Org. Chem. 2026, 22, 205–212, doi:10.3762/bjoc.22.14

• heteroanalogues. These challenges include: (1) the limited availability of suitable substrates, (2) substantial steric hindrance from the terminal ring, making it difficult to introduce substituents at the required positions onto helical precursors, and (3) the complex nature of controlling helical chirality, a

Base-promoted deacylation of 2-acetyl-2,5-dihydrothiophenes and their oxygen-mediated hydroxylation

• Vladimir G. Ilkin,
• Margarita Likhacheva,
• Igor V. Trushkov,
• Tetyana V. Beryozkina,
• Vera S. Berseneva,
• Vladimir T. Abaev,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2026, 22, 192–204, doi:10.3762/bjoc.22.13

• conditions in hand, we have investigated the oxidation of 2-acetyl-2,5-dihydrothiophenes 1, containing various substituents (Scheme 2). Cyclohexano-, cycloheptano- and cyclooctano-spiroannulated 2-acetyl-3-morpholino-N-phenyl-2,5-dihydrothiophene-2-carboxamides 1a,c,f were oxidized into 2-hydroxy derivatives

• the use of 5.0 equiv of sodium in ethanolic solution (3 mL) at rt for 1 h in air (Table 2, entry 5). With optimal conditions in hand, we have investigated the deacylation of acetyldihydrothiophenes 4a–f, containing various substituents (Scheme 4). Thus, cyclohexano-, cyclopentano-, cycloheptano- and

A new synthesis of Tyrian purple (6,6’-dibromoindigo) and its corresponding sulfonate salts

• Holly Helmers,
• Mark Horton,
• Julie Concepcion,
• Jeffrey Bjorklund and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2026, 22, 167–174, doi:10.3762/bjoc.22.10

• not able to be achieved for 1 [25]. The sulfonation of 1 appears to be more challenging than the corresponding sulfonation of indigo, which requires less forcing conditions [25]. This suggests that the bromine substituents deactivate the reactivity of the aromatic ring. As was reported for sulfonated

• color to be retained in its sulfonated derivatives [27][28][29]. As shown in Table 1, the pKa values of 9 and 10 each have first pKa values about 0.4 pK units below their non-brominated derivatives, indicating the impact of the electron-withdrawing halogen substituents [30]. Conclusion Overall, the

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

• optimized conditions established, we investigated the substrate scope of sulfenamides derived from various thiophenols and thiols (Scheme 2). A wide range of phenyl sulfenamides bearing substituents at the para-, meta-, and ortho-positions of the aromatic ring, as well as the unsubstituted parent phenyl

• various acylamides to further evaluate the versatility of this transformation (Scheme 3). The reaction was compatible with a wide range of acyl substituents, including methyl (3t, 91%), isopropyl (3u, 80%), cyclopropyl (3v, 81%), and cyclohexyl (3w, 86%), all of which delivered the corresponding

• sulfinimidate esters in good yields. Encouragingly, the method also tolerated bulky acyl groups such as adamantyl (3x, 88%) and 1-naphthylmethyl (3y, 99%), which underwent smooth conversion without significant steric hindrance. A series of benzamide-derived sulfenamides bearing various substituents on the

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

• % of the catalyst and it was started with Arai-type catalyst A [19]. The features of the catalyst are the quinine moiety with reduced double bond and enhanced halogen-bonding ability due to the highly electronegative substituents on the phenyl ring. The reaction was relatively fast, achieving full

• catalyst and the imine and malonate attacks from si-face affording the product in S-configuration (Figure 2). To demonstrate the utility of the elaborated catalytic system, the Mannich reaction between aromatic imines, both with electron-withdrawing and electron-donating substituents in the phenyl ring

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

• cyclopropane ring is probably a consequence of the formation of a sterically hindered carbanion II in a conformation with an anti-periplanar position of the bulky substituents – bromine and a trichloromethyl group (Scheme 6). Due to the steric reasons, the anion in this conformation is selectively protonated

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

• heterocycles exhibit strong Lewis basicity, potentially complexing and deactivating catalysts. Consequently, the catalytic hydrogenation of six-membered aromatic heterocycles such as pyridine often requires the introduction of substituents or activation of the aromatic heterocycle to facilitate hydrogenation

• 18, 20 to piperidine compounds using [CpRhCl2]2 as a metal catalyst and formic acid as a hydrogen source (Scheme 3) [45]. Different with other previous studies, this method allows for substituents at the 3-position of pyridine, enabling the rapid preparation of chiral piperidine compounds. It should

• ). During attempts to reduce intermediate 181 via asymmetric hydrogen atom transfer (HAT), the authors found that 181 exists as a racemic mixture, with chirality originating from its axially chiral biaryl structure. Owing to the steric hindrance introduced by substituents, 181 exists as a pair of

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

• intramolecular addition to the olefin, affording the cyclized acetal product 4. The reaction proceeded efficiently across a range of substrates bearing various substituents at R¹–R⁴, delivering the desired cyclized products 4a–f in good yields. The proposed mechanism is illustrated in Scheme 1C. Initially

• alkyl iodide 10 were subjected to nickel catalysis in the presence of zirconocene dichloride and zinc dust, intermolecular coupling occurred to afford ketone 12 in good yields. This reaction was applicable to substrates bearing β-alkoxy substituents, which are typically problematic under anionic

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

• α-position, respectively. Compounds 5 represent derivatives with two substituents at the sp3-carbon atoms which sometimes tend to rearrange into the corresponding norcaradiene derivatives [29][30]. Our reactions of anion 2 with electrophiles confirm this tendency – we always observed either a

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

• reaction in which an in situ-generated Vilsmeier reagent converted aryl ketones bearing electron-donating substituents at the ortho- or para-position into alkenyl chlorides [68]. The reported yields corresponded to crude products and therefore do not reflect isolated yields of pure compounds (Scheme 15

• demonstrated that aromatic alkynes can undergo hydrochlorination with good selectivity for the mono-addition when a nitromethane/acetic acid solvent mixture is employed (Scheme 27) [96]. In contrast, selective monohydrochlorination is commonly observed for alkynes bearing coordinating substituents such as

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

• substituents that are labile towards electrophiles. Thus, there is a need for new, more efficient methods for the synthesis of nitro-NNO-azoxy derivatives that do not have the disadvantages of the known approach and allow the use of a wide range of substrates, including various aliphatic ones. Recently, our

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

• compositions of antitumor antibiotics of the kigamycin family include the oxazolo[3,2-a]pyridine skeleton [55][56]. To obtain oxazolopyridones containing trifluoromethyl substituents, the syntheses have been proposed, which are based on the intramolecular cyclization of 1-phenyl-2-(4-(trifluoromethyl)piperidin

• imine reaction center. This makes the center softer, which favors the interaction with the amino group to generate the hexahydropyrimidine intermediate C. The methyl, ethyl and butyl substituents of intermediate B have a positive inductive effect, which increases with the lengthening of the alkyl chain

• piperidone ring, the chemical shifts of axial and equatorial shifts of methylene protons at C(9) are inverted and Δ9ea < 0 (see Table 4, Figure 4). In the 19F NMR spectra, the CF3 group of diastereomeric octahydropyrido[1,2-a]pyrimidinones 4att and 4atc, 4btc with the trans-configuration of the substituents