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

• synthesis of 4 and its possible isomer 3, the required compounds 1 and 2 were synthesized as a mixture of the isomers starting from chromene 5, briefly heated in a closed microwave apparatus with catalytic amounts of acetic acid. Forced heating of 5 in acetic acid or use of stronger acids lead to the

• melifoliones should be synthesized first, to get enough quantity for oxidation to the corresponding quinols in a second experiment. Using the method of Wang and Lee [5], 1 could be prepared regio-specifically in good yield by heating phloroacetophenone and citral in DMF under catalysis of ethylenediammonium

• -position in regard to the OH-group at C-10b (Table 2). Synthesis of melifoliones Melifolione A (1) was prepared according to the method of Wang and Lee [5] by heating phloroacetophenone and citral with ethylene-diammonium diacetate (EDDA) in DMF. However, reaction of the educts in pyridine at 60 °C led to

Structural reassignment of compound 968, an allosteric glutaminase inhibitor

• Lindsey A. Albertelli,
• Sainabou Jallow,
• Chun Li and
• Scott M. Ulrich

Beilstein J. Org. Chem. 2026, 22, 455–460, doi:10.3762/bjoc.22.33

• structure of compound 968 is a benzo[c]phenanthridine 1 or benzo[c]acridine 2 we synthesized it by the reported cyclocondensation reaction, which consists of heating an equimolar mixture of 3-bromo-4-dimethylaminobenzaldehyde, 2-naphthylamine, and dimedone to reflux in 1-butanol. We also purchased compound

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

• homogeneous reduction using tin(II) chloride in ethanol was used after fine-tuning of the published reaction conditions [9]: the reduction was conducted by gentle heating of a mixture of calixarene 11, SnCl2·2H2O, aqueous HCl and ethanol at 70 °C (instead of prolonged boiling of the reaction mixture) in a

• desilylated product in the case of calixarene 22) remained in the reaction mixtures even after their stirring at room temperature for 72 h. In the case of calixarene 22, heating of the mixture at 50 °C for 48 h was enough to complete the process and p-aminocalix[4]arene 25 having two propargyl groups at the

• narrow rim was obtained in 97% yield. Still, the deprotection of calixarene 23 to the desired propargyl ether 26 was far from complete even under heating, which significantly reduced the yield of this compound (Scheme 4). The difference in the efficiency of catalytic removal of the TBS groups observed

Design, synthesis and biological evaluation of 2,5-diaryloxazolo[4,5-d]pyrimidin-7-ylamines as selective cytotoxic agents against HeLa cells

• Maryna V. Kachaeva,
• Agnieszka B. Olejniczak,
• Marta Denel-Bobrowska,
• Victor V. Zhirnov,
• Yevheniia S. Velihina,
• Stepan G. Pilyo and
• Volodymyr S. Brovarets

Beilstein J. Org. Chem. 2026, 22, 390–398, doi:10.3762/bjoc.22.27

• -glucamine). Compounds II were obtained by the sequence of reactions starting from available 2-aryl-4-dichloromethylene-1,3-oxazol-5(4H)-ones I [18]. Thus, treatment of compounds I with arylamidine hydrochlorides in the presence of triethylamine, followed by heating with pyridine, afforded the

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

• and heteromethylation of active methylene β-ketosulfones, promoted by a leaving benzoyl group, is proposed. The primary domino reaction of sarcosine, paraformaldehyde, and β-ketosulfones affords 3-sulfonyl-3-benzoylpyrrolidines in good to high yields. Further treatment with alkyl halides and heating

• cesium carbonate at 25 °C for 96 h provided higher yield (Table 1, entry 2, 70%). However, heating this mixture at 65 °C for 24 h in a sealed vial gave pure desired 4-methoxy-N,N-dimethyl-3-(phenylsulfonyl)butan-1-amine (4a) in 90% yield and 83% overall yield starting from ketosulfone 1a (Table 1, entry

• 4). In attempt to minimize the size of the leaving group we applied a ethoxycarbоnyl moiety instead of the benzoyl group. Thus, heating the dimethylammonium salt of pyrrolidine 2f with an excess of KOH in MeOH for 46 h provided the same product 4a in 89% yield (Table 1, entry 5). While it is

Synthesis of tricyclic fused pyrrolidine nitroxides from 2-alkynylpyrrolidine-1-oxyls

• Mark M. Gulman,
• Yuliya F. Polienko,
• Sofia Yu. Trakhininа,
• Yuri V. Gatilov,
• Tatyana V. Rybalova,
• Sergey A. Dobrynin and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2026, 22, 344–351, doi:10.3762/bjoc.22.22

• propargylamines via A3-coupling reaction [21]. In analogy to a literature procedure [22], heating of radical 2a in a mixture of dimethylamine, formalin, and tetrahydrofuran in the presence of copper(II) acetate afforded the corresponding dimethylamino derivative 2f. To confirm the structure of the novel

• literature data on reactivity of 5-azidopentyne derivatives in intramolecular Huisgen cycloaddition reactions are contradictory. Some authors successfully obtained 5-azidopentyne derivatives upon nucleophilic substitution at 80 °C in DMF, and additional heating at 170 °C was necessary for cyclization to

• previously described for radicals 2a and 2b, but these cyclizations required heating in the presence of a base [16]. To obtain pyrazole derivatives, alkynones 6a,b were treated with hydrazine (Scheme 5). Formation of the pyrazole ring in the reaction of 6b was accompanied by partial hydrazinolysis of the

Ring contraction and ring expansion reactions in terpenoid biosynthesis and their application to total synthesis

• Nicolas Kratena,
• Nicolas Heinzig and
• Peter Gärtner

Beilstein J. Org. Chem. 2026, 22, 289–343, doi:10.3762/bjoc.22.21

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

• -carboxylic acid, thiazolidinecarboxylic acid, and pipecolic acid, in combination with alloxan (1) and maleimides 3, did not lead to the formation of the corresponding cycloadducts. In this work, we also used other dipolarophiles. Under the standard reaction conditions (1,4-dioxane, heating with alloxan and ʟ

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

• the conjugate addition product [50]. The initial addition occurs on the side of the phenol ring opposite (exo) the coordinated metal fragment. Subsequent exposure to a moderate base induces rearomatization. Upon heating, the raspberry ketone 7 is released in high yield (Scheme 1B). The second class of

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

• reactions catalyzed by diverse agents (Scheme 1). For instance, in 2013, Shi et al. described a three-component reaction involving 4-hydroxyquinolin-2(1H)-one, an aromatic aldehyde, and Meldrum’s acid, catalyzed by ʟ-proline under heating [37]. In the same year, Kurosh Rad-Moghadam and co-workers developed

• a related protocol operating at room temperature using the ionic liquid [Bmim]HSO4 as a catalyst, expanding the scope to include aliphatic aldehydes [38]. Later, in 2017, Esmayeel Abbaspour-Gilandeh et al. reported a modified variant of this transformation under solvent-free heating, catalyzed by

• reaction conditions, the lactone forms predominantly (Scheme 1B). However, the lactone appears capable of slow transesterification in the presence of excess alcohol, converting it into the open-chain ester upon prolonged heating. The lower stability of the cyclic product, compared to the open-chain ester

Configuration–packing synergy enabling integrated crystalline-state RTP and amorphous-state TADF

• Ruiyan Wang and
• Yunan Wu

Beilstein J. Org. Chem. 2026, 22, 224–236, doi:10.3762/bjoc.22.16

• phosphorescence emission at room temperature. To further explore this hypothesis, the powder was subjected to heating to its melting point followed by rapid quenching with liquid nitrogen. The resulting solid, after this treatment, was found to show no RTP when examined at room temperature, as demonstrated in

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

• ][8][9]. Analogous to the sulfonation of indigo to synthesize the water-soluble dye indigo carmine, compound 1 was sulfonated to increase its water solubility. Thus, the desired 6,6’-dibromo-5,5’-indigodisulfonic acid disodium salt (9) was obtained by heating 1 in a 2:1 mixture of oleum (20% free SO3

• ) and concentrated sulfuric acid (Scheme 7A). The trisulfonated 6,6’-dibromo-5,5’,7-indigotrisulfonic acid trisodium salt (10) was produced by heating 1 in oleum (20% free SO3), as shown in Scheme 7B. Although monosulfonation of indigo was reported by Sullivan and co-workers, an analogous reaction was

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

• ethynyl-linked coordination sites. Therefore, we prepared a PMMA polymer matrix containing 1 wt % of S/R-Pt to investigate the emission behavior under conditions where molecular motion was suppressed. The PMMA matrix was obtained by dissolving S/R-Pt and PMMA in chloroform under heating at 40 °C, casting

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

• corresponding vic-bis(dithiane) derivatives 16a–d. In 2018, Milsmann et al. reported the dimerization of benzyl bromide using a zirconium complex as a photosensitizer (Scheme 4) [14]. Heating a zirconium precursor with the pincer-type ligand 17, which can be synthesized in three steps from commercially

• . Heating these precursors under flash vacuum pyrolysis conditions at 230 °C led to the removal of the Boc group and intramolecular dehydration–condensation, thereby constructing the diketopiperazine core and enabling the total syntheses of ditryptophenaline (70), dibrevianamide F (71), and tetratryptomycin

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

• high-yielding synthesis of 23 by heating diketone 22 with PCl5 for several hours in toluene (Scheme 6B) [52]. Similarly, Jung obtained 25 in 69% yield after heating neat ketone and PCl5 (Scheme 6C) [53]. The high yield of 25 is somewhat surprising, considering the limited stability thereof. In our

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

• iodoindoles 25–28 in 68–79% yields (Scheme 5). Negishi cross-coupling according to Jackson et al. [39] with the organozinc reagent prepared from 29 gave the adducts 30–33 in 42–55% yields. Removal of the Fmoc and N-acetyl groups with piperidine gave the corresponding anthranilamides, which upon heating with

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

• 5att (δF 79.74 ppm) (Table 1, entries 1–4). The synthesis in 1,4-dioxane resulted in the highest conversion and the least amount of by-products, but the reaction proceeded slowly over four days. To speed up the process, the synthesis in dioxane was carried out by heating at 60 °C (Table 1, entry 5) in

• a microwave (MW) reactor (Table 1, entry 6). It turned out that after 24 hours of heating the complete conversion of oxo ester 1 occurred and the overall yield increased to 83% (Table 1, entry 5), whereas the use of MW reduced the reaction time down to five hours (Table 1, entry 6), but the contents

• of by-products were observed to increase to 23%. Under all conditions used, the predominant formation of the trans,trans-diastereomeric form of octahydropyrido[1,2-a]pyrimidin-6-one 4att was observed (with the maximum amount of 33% in polar MeCN). Heating in dioxane affected the diastereomeric

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

• transformed into rockogenin 12-methanesulfonate-3-pivalate (89) by reduction and mesylation. Heating to reflux in anhydrous pyridine afforded the rearrangement to the C-nor-D-homo isosteroid skeleton 90 with an exocyclic 13,18-double bond in 5 steps from hecogenin acetate (see Scheme 29). In a five-step

• corresponding to deprotonation at C14 was observed. The elimination to the enal did not occur spontaneously but required heating of the corresponding C12-mesylate, hinting at the ring strain accompanied by formation of the double bond in the trans-hydrindane system. The enal was subjected to a Wittig

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

• –transmission spinner stage (1 rps sample rotation speed) and measured in transmission mode using Cu Kα (1.541874 Å) radiation in the 2.0000–34.9964° 2θ range with 0.0131° 2θ step size and continuous gonio (θ/θ) scan in 1 measurement cycle. 45 kV accelerating voltage and 40 mA anode heating current were used

• . Diffraction intensity was measured by a PIXcel 3D 1 × 1 area detector. Thermogravimetric (TG) curves of amorphous samples (21b, 38d, 54f) were measured by a TA Instruments Discovery TGA thermogravimetric analyzer in the 30–200 °C temperature range with a 10 °C/min heating rate using 11 to 12 mg sample in a

• 100 μL platinum pan in 25 mL/min nitrogen atmosphere. Melting properties of the amorphous samples (21b, 38d, 54f) were also studied by a TA Instruments Discovery DSC differential scanning calorimeter in the 25–120 °C temperature range with a 10 °C/min heating rate using 2.5 to 3.0 mg sample in a

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

• 10.3762/bjoc.21.203 Abstract Various 5-arylidene derivatives were prepared via a Knoevenagel condensation-type reaction of aromatic/heteroaromatic aldehydes with rhodanine or thiazolidine-2,4-dione (TZD) catalyzed by EDA/AcOH under microwave heating. This convenient methodology is broad in scope (49

• condensation-type reaction using ethylenediamine (EDA) as catalyst in AcOH under microwave (μw) heating. This convenient methodology is broad in scope, provides the condensation products in high yields (up to 99%), with a reasonable catalyst loading (10 mol %) in only 30 minutes. This approach also enabled the

• . Photophysical studies indicated a fluorescence mechanism via intramolecular charge transfer (ICT). Results and Discussion Synthesis of 5-arylidene derivatives under microwave heating To find the ideal reaction conditions for the synthesis of 5-arylidene derivatives, benzaldehyde (1a) and rhodanine (2a) were

Silica gel with covalently attached bambusuril macrocycle for dicyanoaurate sorption from water

• Michaela Šusterová and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2025, 21, 2604–2611, doi:10.3762/bjoc.21.201

• example, an amphiphilic poly(methyl methacrylate)-based polymer modified with calix[4]pyrrole was found to form micelles in water that capture anions from caesium salts and can be precipitated from solution upon heating [11]. Similarly, a hydrogel composed of poly(vinyl alcohol) cross-linked by a “Texas

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

• reaction of 87 was employed, generating both the kinetic product 88 and the desired thermodynamic product 89. Heating 88 promoted a retro-Diels–Alder/Diels–Alder equilibrium, favoring the more stable isomer 89. Palladium-catalyzed hydrogenation of the 1,2-disubstituted alkene in 89, followed by Mo(CO)6

• 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

Pentacyclic aromatic heterocycles from Pd-catalyzed annulation of 1,5-diaryl-1,2,3-triazoles

• Kaylen D. Lathrum,
• Emily M. Hanneken,
• Katelyn R. Grzelak and
• James T. Fletcher

Beilstein J. Org. Chem. 2025, 21, 2524–2534, doi:10.3762/bjoc.21.194

• -connected ortho-bromobenzene subunit analogs failed under microwave irradiation but were successful using conventional thermal heating in yields of 31–65%. The expanded nature of the aromatic ring system following annulation was reflected by the downfield shifting of aromatic 1H NMR signals and the red

• tandem approach preparing 7–12 ranged from 43–85%, which were similar to running the deprotection and cycloaddition reactions sequentially. Pd-catalyzed annulation using a modification of previously reported reaction conditions [46] under microwave irradiation instead of thermal heating converted 1,5

• thermal heating conditions [46] was successful for preparing these compounds. Yields of annulation reactions for the naphthalene-containing analog 31 (65%) was once again appreciably higher than that of the quinoline and isoquinoline derivatives 32–36 (31–51%), but there appeared to be no significant

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

• perform equally well using conventional heating methods. Aniline 10 and carboxylic acid 13 were combined under standard (HBTU) amide coupling conditions to afford benzyl ester 14 in 52% yield. Compound 14 was subsequently debenzylated via hydrogenolysis to afford the target Db2 monomer 15 in 77% yield

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

• heating, to membrane permeabilization and dye release (Supporting Information File 1, Figures S12 and S13). In LUVs composed solely of EYPC, azobenzene photoisomerization in rotaxane 1 leads to 70% sulforhodamine B release (Table 1, Figure 4b, and Supporting Information File 1, Figure S14), comparable to

• rotaxane 1-Z would convert to 1-E over that timescale. Nevertheless, the results clearly show that heating above Tm enhances release. We next evaluated the effect of light irradiation on rotaxane 1 in DPPC. At 25 °C, the initial addition of 1-Z resulted in only a 3% release after 5 minutes. Irradiation at

• same amount of DMSO but no axle over five irradiation cycles alternating 370 nm and 467 nm light. As seen in Figure 7a, the release occurs only in vesicles containing axle 3, ruling out nonspecific effects such as membrane degradation from direct light exposure or solvent heating (HEPES buffer and