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

• become quite attractive structural motifs in drug design [13][14]. A few examples are shown in Figure 3: oxetano-thalidomide 1 was designed as an analogue of the infamous thalidomide to block racemisation and hence prevent the severe side-effects caused by the opposite enantiomer [15]. Compound 2 is a

• alkenes and high diastereocontrol (dr ≥ 80:20) was achieved for trisubstituted ones. Switching the bromonium activator to the iodonium analogue only led to a lower yield. This haloetherification method was further expanded by McLaughlin and Roberts in 2022 who reported a convenient two-step sequence

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80

• part of this review, see Table 3). Cooling leads to a reduction of the intensity of the central EPR signal, fine structure, and significant diradical anisotropy, indicating that the triplet state becomes less and less populated (see Figure 12b) [95]. By contrast, the TTM-TTM analogue without chlorine

Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline

• Benedek Batizi,
• Patrik Pollák,
• András Dancsó,
• Péter Keglevich,
• Gyula Simig,
• Balázs Volk and
• Mátyás Milen

Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79

• brevicarine (2, isolated as its dihydrochloride salt). Based on the above results, Eschweiler–Clarke methylation of primary amine 25 was applied for the synthesis of N-methylbrevicarine (27) [39], a close structural analogue of alkaloid 2. The NMR data of our synthesized brevicarine (2) base and

Synthesis and photoinduced switching properties of C₇-heteroatom containing push–pull norbornadiene derivatives

• Daniel Krappmann and
• Andreas Hirsch

Beilstein J. Org. Chem. 2025, 21, 807–816, doi:10.3762/bjoc.21.64

• -NBD2 (Supporting Information File 1), demonstrating the intermediate availability of O-QC2. In a similar manner, the aza analogue N-NBD2 was investigated. The UV–vis experiments (Figure 4) yielded results comparable to those obtained for N-NBD1. Initially, the conversion to N-QC2 is anticipated at

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• molecular dipole moment of 1.90 D. In contrast, the monofluorinated analogue 2 can access three different staggered rotamers 2a–c about the C–C(F) bond; all three of these rotamers have similar energies, but their molecular dipole moments vary considerably depending on whether the C–F dipole is aligned with

• or against the dipole of the indole moiety. A similar phenomenon occurs with the difluorinated analogue 3. The fluorinated molecules 2 and 3 can be said to have a “chameleonic” character [9][10][11][12][13][14]: they have the ability to change polarity to suit their environment. This is a potentially

• favourable accommodation of a wider C–C(F2)–C angle within the cyclic product 11. Another illustration of the geometric perturbation caused by the wider C–C(F2)–C angle comes from the stearic acids 12 and 13 (Figure 3); the gem-difluorinated analogue 13 has substantially greater conformational disorder

Binding of tryptophan and tryptophan-containing peptides in water by a glucose naphtho crown ether

• Gianpaolo Gallo and
• Bartosz Lewandowski

Beilstein J. Org. Chem. 2025, 21, 541–546, doi:10.3762/bjoc.21.42

• ). Peptide 7, the acetylated analogue of 4, is bound by 1 with essentially the same affinity as the non-acetylated variant (entry 6, Table 2). Peptide 8, consisting of three alanine residues, is bound by the glucose naphtho crown ether with a significantly lower affinity, 3–4 times weaker than the Trp

Deep-blue emitting 9,10-bis(perfluorobenzyl)anthracene

• Long K. San,
• Sebastian Balser,
• Brian J. Reeves,
• Tyler T. Clikeman,
• Yu-Sheng Chen,
• Steven H. Strauss and
• Olga V. Boltalina

Beilstein J. Org. Chem. 2025, 21, 515–525, doi:10.3762/bjoc.21.39

• , the size and conformational flexibility of the five BnF groups resulted in significant disruption of CORA–CORA π–π interactions due to the greater CORA–CORA bowl-to-bowl distances relative to the less bulky C5-CORA(CF3)5 analogue [18][19]. However, corannulene derivatives are only weakly fluorescent

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• rotate in this form [41], the structure can be termed rigid. Nonetheless, slight variations in the cavity height can be controlled by engineering the twist along the triptycene axis. For instance, comparing crystal structures of cage 2 and its monoacetylated analogue, 2Ac1 (Figure 9B), a decrease of 0.3

Oxidation of [3]naphthylenes to cations and dications converts local paratropicity into global diatropicity

• Abel Cárdenas,
• Zexin Jin,
• Yong Ni,
• Jishan Wu,
• Yan Xia,
• Francisco Javier Ramírez and
• Juan Casado

Beilstein J. Org. Chem. 2025, 21, 277–285, doi:10.3762/bjoc.21.20

• (Figure 6) seems to preserve the punctual group of its linear analogue, especially concerning the outermost NAP moieties. Interestingly, this quasi-D2h symmetry is broken upon oxidation, which is supported by the appearance of the triplet of Raman bands in the 1600–1550 cm−1 region. On the other hand, the

Effect of substitution position of aryl groups on the thermal back reactivity of aza-diarylethene photoswitches and prediction by density functional theory

• Misato Suganuma,
• Daichi Kitagawa,
• Shota Hamatani and
• Seiya Kobatake

Beilstein J. Org. Chem. 2025, 21, 242–252, doi:10.3762/bjoc.21.16

• effective methods for predicting the thermal back reactivity, density functional theory (DFT) calculations can be considered [51][58][59][60][61][62]. For example, in previous studies on the thermal back reactivity of diarylbenzene that is an analogue of diarylethene, we found that the M06-2X level of

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• ]. One of the most studied and inexpensive routes to synthesize substituted phenethylamines focuses on the reduction of their α,β-unsaturated nitroalkene analogue (β-nitrostyrene), where both the double bond and the nitro group need to be reduced to deliver the corresponding primary amine. Their

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• from certain plant species (Figure 1) [12]. The acenaphthylene-fused thiophene-based heteroarene 3 is another heterocyclic fluoranthene analogue, which was used as an organic semiconductor in transistors [13]. The synthesis and coordination complexes of the acenaphthylene-fused N-heterocyclic (NHC

• 1,8-diiodonaphthalene (12) and a broad range of arylboronic acids and esters to afford substituted fluoranthenes 13 in good to high yields (Scheme 1d) [43]. In that work, we had only one example of a heterocyclic fluoranthene analogue where the use of 4-pyridylboronic acid provided the corresponding

• the targeted benzo[j]fluoranthene product 32 was isolated in 45% yield. It should be noted that this reaction was not successful when an analogue of compound 31 with -OTIPS instead of the -OMOM group was tested as the boronic ester reaction partner, due to the decomposition of this compound presumably

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• /CH2Cl2 at room temperature (17% yield). Subjecting the methoxylated benzaldehyde intermediate 9 to a Doebner–Knoevenagel condensation with malonic acid and pyridine afforded the brominated cinnamic acid analogue 10 in 54% yield [19]. Amidation chemistry using carbonyldiimidazole (CDI) [18] and the

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• . The authors proposed a mechanism for the reaction, in which the alkene is activated by PhI(OAc)2, followed by intramolecular nucleophilic attack of nitrogen and displacement of iodobenzene by fluoride. The intramolecular aminofluorination of unsaturated amines using a structural analogue of Togni’s

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• trichloroacetimidate 10e by reaction with hydrazine and subsequent treatment with trichloroacetonitrile. The same synthesis was carried out also with the β-configured analogue of 10a. However, employment of the α-anomer 10a proved to be advantageous in terms of yield. The reaction of 1d with 10e afforded indigo-N

Investigation of a bimetallic terbium(III)/copper(II) chemosensor for the detection of aqueous hydrogen sulfide

• Parvathy Mini,
• Michael R. Grace,
• Genevieve H. Dennison and
• Kellie L. Tuck

Beilstein J. Org. Chem. 2024, 20, 2818–2826, doi:10.3762/bjoc.20.237

• addition of 3.0 equivalents of HS−(aq) ions. The calculated theoretical LoD was 0.63 μM (20 ppb), which is comparable to that observed with the europium(III) analogue (1.1 μM, 36 ppb) [16]). The chemosensor exhibited significant reversibility over multiple cycles involving the addition and subsequent

• upon our previously reported findings. Our earlier work demonstrated an increase in europium luminescence with a LoD of 100 ppb and 665 ppb for two Eu analogues [Eu(triazole-DPA)3·3Cu]3+ [16] and [Eu(DO2A)DPA·Cu]+ [17], while the [Tb(DO2A)DPA·Cu]+ analogue [17] exhibited no significant change in

• emission spectrum, unlike that observed with the europium(III) analogue. This result suggests potential variations in the luminescence response among terbium(III) analogues and highlights the complexity of the interaction between lanthanide complexes and gaseous H2S, and understanding the nuances of this

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• -analogue porphyrin 35. Use of the electron-donating p-tolylboronic acid (20), resulted in a 30% yield (Table 2, entry 12) again requiring an increase of catalyst loading and a change of base to K3PO4. Heterocyclic boronic acids/esters were again investigated for coupling reactivity with a consistent trend

• a magnitude of ≈0.3 Å less ruffling when compared to that of the meta-substituted porphyrin 37. In terms of meta-phenyl-substituted porphyrin 36 a contribution of ruffling is observed, but no ruffling is observed in the planar analogue. Crystal packing analysis of arm-extended para-substituted

Synthesis and cytotoxicity studies of novel N-arylbenzo[h]quinazolin-2-amines

• Battini Veeraiah,
• Kishore Ramineni,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Hélène Solhi,
• Rémy Le Guevel,
• Chada Raji Reddy,
• Frédéric Justaud and
• René Grée

Beilstein J. Org. Chem. 2024, 20, 2592–2598, doi:10.3762/bjoc.20.218

• particular for 4a which has demonstrated low micromolar toxicities (IC50 from 1.7 to 6 μM) against HuH-7, Caco-2, MDA-MB-468 and HCT-116 cells, with low to no action, on the other cells. Similarly, the meta-fluoro analogue 4i is active only on Caco-2, MDA-MB-468, HCT-116 and MCF7 (IC50 from 2 to 6 μM) while

Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• to be confirmed by single-crystal diffraction analysis (see below) [33]. Unfortunately, trifluorinated analogue 12 was not crystalline. Thus, we removed the acetyl protecting groups and generated the corresponding p-bromobenzoate derivative 17 to obtain suitable crystalline material [24][34]. In

• = 180° is the 1C4 chair. The distortion of the chair conformation increases with the size of the halogen at C4. Surprisingly, the trifluorinated analogue is less distorted than the non-halogenated talopyranose. The meridian angle (φ) indicates the nature of the distortion. The distortion of the

• trifluorinated analogue is in a direction somewhat between an E5 conformation (φ ≈ 300°) and a OH5 conformation (φ ≈ 330°). The other trihalogenated analogues are distorted towards an E5 conformation (φ ≈ 300°). The distortion of the non-halogenated talopyranose is in the direction on an 4E conformation (φ ≈ 240

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• (40.39 ± 0.89 μM), in which the sulfur atom is directly bonded to the aromatic ring. The IC50 value is 63.48 ± 1.08 μM for compound 4. The appearance of a phenyl substituent in the thiazole ring affects negatively the antiradical ability of compound 4 compared to its unsubstituted analogue CatH2-CH2-S

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• the desired protein coverage and robustness. Still, the critical part of the process starts with the careful design of a NP analogue and selection of the proper biological system, which may include animal models, 3D tissue-organoids, or 2D cell culture. Depending on the project aim, which typically

• analogue, the DMP-tag, which in contrast to standardly used isotopic tags bearing the N-hydroxysuccinimide ester (NHS-ester) reacting with all primary amines of lysine side-chains, allows to selectively label the probe–protein conjugates (Figure 7A) [81][83]. The DMP-tag can be prepared in a six-steps

O,S,Se-containing Biginelli products based on cyclic β-ketosulfone and their postfunctionalization

• Kateryna V. Dil and
• Vitalii A. Palchykov

Beilstein J. Org. Chem. 2024, 20, 2143–2151, doi:10.3762/bjoc.20.184

• regioselectivity to give diverse DHPMs in reasonable yields up to 95%. Moreover, an SO2-containing analogue of anticancer drug-candidate enastron (SO2 vs C=O) was obtained by using the here reported method in gram scale. We also demonstrate the reactivity of the Biginelli product in various directions – synthesis

• Supporting Information File 1). Next, we paid attention to testing the conditions we developed for the synthesis of the SO2-containing analogue 2r of potent anticancer drug enastron in gram scale (Scheme 3). Enastron is a novel dihydropyrimidine-based mitotic kinesin spindle protein KSP/Eg5 inhibitor [36

• -4,6,7,8-tetrahydro-1H-thiopyrano[3,2-d]pyrimidine-2(3H)-one/thione/selenone 5,5-dioxides and some of their derivatives. Furthermore, this methodology was successfully applied for the synthesis of the SO2-containing analogue of the anticancer drug-candidate enastron (SO2 vs C=O), and we believe a multitude

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• prolinamide-thiourea organocatalyst onto commercially available resins (JandaJel, polystyrene-divinylbenzene, and ChemMatrix) results in diminished catalytic activity, both in terms of yield and enantiomeric excess values, compared to the homogeneous analogue [117]. On the contrary, Dumesic and co-workers

2-Heteroarylethylamines in medicinal chemistry: a review of 2-phenethylamine satellite chemical space

• Carlos Nieto,
• Alejandro Manchado,
• Ángel García-González,
• David Díez and
• Narciso M. Garrido

Beilstein J. Org. Chem. 2024, 20, 1880–1893, doi:10.3762/bjoc.20.163

• replacements leading to novel MAO-A bioactive entities [16][17]. The brominated analogue 8 showed moderate MAO-A activity compared to the parent 2-furyl compound 7, as a result of increased polarizability. The condensed benzofuran 9 revealed submicromolar MAO-A potency, a resemblance to the indole system of 5

• importance and applications of ring-modified histidines, Sharma et al. [66] reviewed the design, synthesis, and medicinal chemistry of these motifs covering antimicrobial, antiplasmodial, CNS and anticancer applications among others. Pyrazoles: Betazole (95) is a pyrazole-like histamine analogue with H2