Hydrogen-bonded macrocycle-mediated dimerization for orthogonal supramolecular polymerization

• Wentao Yu,
• Zhiyao Yang,
• Chengkan Yu,
• Xiaowei Li and
• Lihua Yuan

Beilstein J. Org. Chem. 2025, 21, 179–188, doi:10.3762/bjoc.21.10

• noncovalent bonding interactions. It also confers on supramolecular assemblies with higher complexity and multilevel ordering [9][10][11], leading to a vast number of applications, for example, for use in detection and separation [12], sensing [13], photocatalysis [14], release [15], and as thermochromic and

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• activation, atroposelective aza-Michael addition, and intramolecular aldol reaction to form the cationic intermediate Int-6. Release of the catalyst C2, reduction with NaBH4, and dehydration with acetic acid leads to the desired product 6. Recently, an organocatalytic atroposelective intramolecular (4 + 2

• intermediate Int-9. As the assumed rate-determining step the intramolecular nucleophilic addition takes place, followed by further cyclization and finally, release of the organocatalyst to form the axially chiral product 9. Various aryl-substituted indolines 9 were obtained in good yields and high enantiomeric

• dehydration, release of the chiral acid, and aromatization through tautomerization of intermediate Int-50 generate the desired product 195. Kwon et al. compared the effectivity of traditional biaryl phosphoric acid C30 with peptide phosphoric acid C46 in the cyclodehydration of trifluorophenylaminoacetals

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• , characterized by a concave shape with a central cavity [1]. Such structures hold significant potential for drug delivery applications as nanomotors, offering both encapsulation capability and controlled release functionalities [2][3]. Moreover, researchers have explored novel shapes utilizing PEG-PS copolymers

• holds profound implications for drug delivery and beyond. By tailoring vesicle morphology to specific requirements, researchers can optimize drug encapsulation, targeting, and release, advancing the efficacy and precision of therapeutic interventions. Continued exploration of these versatile materials

• , triggering the release of water molecules from the hydrophilic layer. Consequently, enhanced interactions between polysarcosine chains ensue, culminating in a more rigid and less permeable membrane structure at an optimum dehydration at 70 °C. This augmented membrane permeability facilitates the buildup of

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• synaptic vesicle protein that is required for normal synaptic function, interfering with the release of the neurotransmitter [71][72]. Ugi reaction: Cioc et al. [73] recognized the 2-oxo-1-pyrrolidino acetamide structure of levetiracetam as a potential Ugi scaffold and aimed to construct racetam

Controlled oligomerization of [1.1.1]propellane through radical polarity matching: selective synthesis of SF₅- and CF₃SF₄-containing [2]staffanes

• Jón Atiba Buldt,
• Wang-Yeuk Kong,
• Yannick Kraemer,
• Masiel M. Belsuzarri,
• Ansh Hiten Patel,
• James C. Fettinger,
• Dean J. Tantillo and
• Cody Ross Pitts

Beilstein J. Org. Chem. 2024, 20, 3134–3143, doi:10.3762/bjoc.20.259

• -containing [2]staffane in the solid state. Keywords: pentafluorosulfanylation; [1.1.1]propellane; radical chain oligomerization; staffanes; strain-release; Introduction In various radical additions of X–Y across [1.1.1]propellane (1), functionalized oligomers known as [n]staffanes – with n > 1, where n

• synthetic challenge. Herein, we report proof-of-concept that our previous work on strain-release pentafluorosulfanylation of 1 [36] using SF5Cl (prepared in house [37] under mild oxidative fluorination conditions [38][39][40][41][42][43][44]) can be extended to the selective synthesis of the associated

• cooling; this highlights that the [2]staffanes synthesized during this study are also interesting from a fundamental structural standpoint. Results and Discussion Over the past few years, our group has begun to establish strain-release pentafluorosulfanylation as a viable strategy for C(sp3)–SF5 bond

Extension of the π-system of monoaryl-substituted norbornadienes with acetylene bridges: influence on the photochemical conversion and storage of light energy

• Robin Schulte,
• Dustin Schade,
• Thomas Paululat,
• Till J. B. Zähringer,
• Christoph Kerzig and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 3061–3068, doi:10.3762/bjoc.20.254

• converted into photoisomers with higher energy upon absorption of light. In turn, this reaction is reversible, thus allowing to release the stored chemical energy as heat in a specifically triggered back reaction [7][8][10][11][12][13]. For a practicable MOST system, some key parameters have to be ensured

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• thioesterase (TE) domain and determines the topology of the final NRP product. The TE may release the NRP as a linear peptide or cyclic peptide, and the latter further manifests many possible topologies (Figure 5b). In a nutshell, offloading is a TE-catalyzed nucleophilic attack to release an NRP from the

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• the entire solution derived from the release of the dumbbell 13 after the decrosslinking. This fluorescence wavelength change was induced by the solvation of the dye moieties. Since the dumbbell contains the push-pull type substituents on the biphenyl structure, this dye showed solvatochromism

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• subsequent β C–C scission of radical B produces the β-keto radical E, driven by strain release. Further alkene 127 adds the β-keto radical E to form the C-centered radical F. The Fe(III)OO-t-Bu complex D resulted from the Fe(II)/Fe(III) catalytic cycle reacts with radical F to yield the target product 129. A

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

• carbohydrate moiety is later hydrolytically cleaved in the cell to release the indirubin which then acts as a CDK inhibitor. A synergistic effect of plasma-activated medium (PAM) and β-33b on human skin cancer cells was observed [32][33]. With regard to viability, adhesion capacity, apoptosis and G2/M cell

• negative feed-back loop by TRAIL and an upregulation of both receptors. In addition, a loss of mitochondrial membrane potential and release of cytochrome c was observed which gave rise to an activation of intrinsic apoptosis pathways. The mitochondrial response seems to be related to an upregulation of Bax

Mechanochemical difluoromethylations of ketones

• Jinbo Ke,
• Pit van Bonn and
• Carsten Bolm

Beilstein J. Org. Chem. 2024, 20, 2799–2805, doi:10.3762/bjoc.20.235

• -depleting sulfur dioxide as side products [46][47]. Later, Ichikawa and co-workers established the release of difluorocarbene from TFDA with catalytic amounts of an N-heterocyclic carbene and a base (Scheme 1C) [29][48][49]. In these reactions, difluoromethyl enol ethers were obtained, which were

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• enolization of benzofuranone 3 in the presence of a base produced intermediate A. The latter reacted with hydroperoxide to form B with the concomitant generation of the radicals, which further reacted with intermediate B to form intermediate C. Finally, C is hydrolysed with the release of one molecule CO2 and

Deciphering the mechanism of γ-cyclodextrin’s hydrophobic cavity hydration: an integrated experimental and theoretical study

• Stiliyana Pereva,
• Stefan Dobrev,
• Tsveta Sarafska,
• Valya Nikolova,
• Silvia Angelova,
• Tony Spassov and
• Todor Dudev

Beilstein J. Org. Chem. 2024, 20, 2635–2643, doi:10.3762/bjoc.20.221

• contains 7.1 water molecules, which occupy 14 sites [24]. Literature TG data show a 7.2% mass loss up to 105 °C, with a peak maximum at 63.4 °C, corresponding to the water release [25]. DSC data correlate with the TG results, revealing an endothermic peak related to the water release at 80.9 °C [25]. In

• a maximum at about 365 K associated with the release of crystal water. The enthalpy change due to water release from γ-CD was determined to be 112 J g−1 (20.5 kJ mol−1 H2O). This value is lower than that (35–40 kJ mol−1 H2O) obtained for β-CD [14] and that found by Bilal et al. [26] and appears

• similar to the value experimentally obtained for α-CD (22.1 ± 3.8 and 30.0 ± 2.5 kJ mol−1 H2O for the first and second water release, respectively) [13]. The thermogravimetric curve shows a 10% weight loss in the temperature range 300–450 K, associated with the release of both crystal water inside the

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• anodic oxidation cleaves the diazene, resulting in the formation of an acyl radical and the release of molecular nitrogen. The subsequent step involves the decarboxylation of the acyl radical to produce an alkyl radical. This method was successfully applied to the late-stage functionalization of

Phenylseleno trifluoromethoxylation of alkenes

• Clément Delobel,
• Armen Panossian,
• Gilles Hanquet,
• Frédéric R. Leroux,
• Fabien Toulgoat and
• Thierry Billard

Beilstein J. Org. Chem. 2024, 20, 2434–2441, doi:10.3762/bjoc.20.207

• resulting from the substitution of the CF3O group by the trifluoroacetoxy group was then observed. The activation of a fluorine atom from the CF3O group by H+ could be envisaged, which would then trigger the selenium attack to release difluorophosgene and HF, thus generating an episelenonium, which would

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• release catalyst 78 completing the catalytic cycle (Scheme 17). In a mechanistic probe, the proposed reaction intermediates were used as starting electrophiles under the standard reaction conditions (Scheme 18). In all three cases, identical outcomes were achieved, supporting the proposed catalytic cycle

Tandem diazotization/cyclization approach for the synthesis of a fused 1,2,3-triazinone-furazan/furoxan heterocyclic system

• Yuri A. Sidunets,
• Valeriya G. Melekhina and
• Leonid L. Fershtat

Beilstein J. Org. Chem. 2024, 20, 2342–2348, doi:10.3762/bjoc.20.200

• conducted a series of studies. Thus, due to the presence of a furoxan fragment, triazinones 1 can act as NO-donors. To assess their NO-release capability, compounds 1 were kept for 1 hour under physiological conditions (pH 7.4, 37 °C), then Griess reagent was added and studied by spectrophotometry (this

• ). NO release data. Tandem diazotization/azo coupling reactions of (1,2,5-oxadiazolyl)carboxamides containing an amino functionality. Synthesis of target furoxanotriazinones 1a–h. The synthesis of furazanotriazinones 7a–h. Control experiment with Na15NO2. Optimization of the diazotization of amide 2aa

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 linkers were proposed and designed to mainly facilitate the enrichment of the probe–protein or probe–peptide conjugates and their selective release after enrichment. In this review we would like to highlight the fragmentation properties of the different linkers and resulting ions as the valuable

• proteome and enrichment-based methods. There are several chemical proteomics linkers reported that improve ionization of the probe–peptide conjugates or release a reporter ion during fragmentation or both (Figure 7). The reporter ion is important as it may serve two purposes. First, it facilitates the

• -step synthesis. However, in comparison to the DMP-tag or AzidoTMT the release of the reporter ion from the SOX-tag has somewhat lower intensity. Calle et al. designed, synthesized, and validated a series of ‘clickable’ linkers for characterization of protein O-glycosylation containing positively

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• , which add to isocyanides to form the imidoyl radicals. The capture of the imidoyl radicals with the azido group proceeds with the release of N2, and the amino radical formed abstracts hydrogen from the surroundings (Scheme 17a and 17b) [61]. The imidoyl radical formed by the addition of Ph2P(O)• to

• addition of radical species to the isocyano group of 29 to form the imidoyl radical 30 as a key intermediate, which adds intramolecularly to the ortho-aryl group. The subsequent aromatization with the release of hydrogen (or proton) affords 31 in good yields. Nanni et al. reported the reaction of 2

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• then undergoes a proton shift to provide intermediate B. Intermediate B collapses via reductive elimination to give nitrenium ion C, along with the release of iodobenzene and sulfamate. Finally, nucleophilic attack of the olefin moiety of C on the electrophilic nitrogen atom, followed by the

• migration and reductive elimination, along with the release of iodobenzene and sulfamic acid. Cyclization of protonated G takes place to afford the intermediate H. Finally, release of water and β-proton elimination produces the rearranged product 3a (Scheme 8). Conclusion In summary, we reported the

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

• improvement through inverse agonism at histamine receptor 3 (H3) using recombinant isoforms. This finding corrects their previous assumption of betahistidine acting as an antagonist. Inhibition of cAMP formation and [3H]arachidonic acid release concluded the inverse agonist role. Five-membered heteroaromatic

• of Th1 cytokine, leukotriene and chemokines release, or IL-6 induction. Histamine targets histamine receptors H1–4, triggering pro-inflammatory or anti-inflammatory events depending on the receptor type and cells involved [45][49]. Histamine also plays a critical role in both vertebrates and

• -ring bioisostere, but as carboxylic acid one, Schwarz et al. [79] developed tetrazole-based pregabalin bioisosteres 113–118 (Scheme 18). The target protein α2-δ is involved in neurotransmitters release reduction, as a model of anxiety and neuropathic pain. In general, submicromolar affinities were

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• then reacted with a different isocyanide (R4–NC) in the presence of a palladium catalyst. The release of nitrogen from intermediates I resulted in nitrenes II, which in turn involved in the intramolecular transfer to yield species III. The carbodiimides IV, which were formed through reductive

Synthesis of polycyclic aromatic quinones by continuous flow electrochemical oxidation: anodic methoxylation of polycyclic aromatic phenols (PAPs)

• Hiwot M. Tiruye,
• Solon Economopoulos and
• Kåre B. Jørgensen

Beilstein J. Org. Chem. 2024, 20, 1746–1757, doi:10.3762/bjoc.20.153

• flowrate of 100 µL/min. The current was increased from 1 mA to 13 mA to increase the electron equivalents from 1 F/mol to 8 F/mol at a potential of 1.7–3.0 V. The crudes, after evaporation of the solvents, were further hydrolysed with a mixture of HCl, acetic acid, and water to release the quinones before