Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• under the umbrella of C1 chemistry was to provide a straightforward access to the privileged scaffold of fused heteroannulated pyrimidones, which demonstrate a broad range of biological activities [28][29][30][31][32][33][34][35], including use as emissive nucleoside analogues [36][37][38]. Moreover

• was observed at an average wavelength of 384 nm for 5a–e, 439 nm for 6a–e and 430 nm for 7a–e (see Supporting Information File 1 for detailed information). In support of the proposed scaffold 7b, we were able to solve its crystal structure (Figure 3). An intermolecular bifurcated hydrogen bond network

• pyrimidine scaffold. Representative fluorescence spectrum of compounds 5b (λex = 330 nm) and 6e (λex = 430 nm) at 0.2 M in DMSO. Molecular geometry observed within the crystal structure of compound 7b (CCDC 2376493). Strategies towards targeted adducts: A) Niementowski quinazoline synthesis utilizing

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• , styrene derivatives bearing both electron-rich and electron-poor groups underwent the desired transformation with high yields and enantioselectivities (23g and 23h). However, the styrene scaffold bearing a trifluoromethyl group showed reduced enantioselectivity (23i). Styrenes containing heterocyclic

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• reactions starting from different reagents. In a first approach proposed by Meshram and co-workers, pyridin-2-one, O-tosylhydroxylamine and acetophenone treated in an ionic liquid assembled through the cascade formation of three C–N bonds to give the imidazo[1,2-a]pyridine scaffold 33 (Scheme 25) [43]. The

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

• ; phenethylamine; Introduction The phenethylamine scaffold represents a recurring motif among natural and synthetic drug molecules. The latter are mainly constituted by a varied class of substituted phenylethylamines exhibiting psychoactive properties, and typically employed for medical and recreational use [1][2

Ceratinadin G, a new psammaplysin derivative possessing a cyano group from a sponge of the genus Pseudoceratina

• Shin-ichiro Kurimoto,
• Kouta Inoue,
• Taito Ohno and
• Takaaki Kubota

Beilstein J. Org. Chem. 2024, 20, 3215–3220, doi:10.3762/bjoc.20.267

• a rare nitrile that contains a cyano group as aminoacetonitrile. The biosynthesis of the 8,10-dibromo-9-methoxy-1,6-dioxa-2-azaspiro[4.6]undeca-2,7,9-trien-4-ol scaffold has been proposed by Scheuer, Clardy and co-workers [5], but how the cyano group in 1 is biosynthesized remains unknown and is of

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

• from the amide proton linked the propyl-2-pyrrolidine moiety to the brominated acrylamide fragment and thus the full chemical structure of 4 was elucidated and assigned to ianthelliformisamine D. A refined literature search using Scifinder Scholar [16] revealed that compound 4 contains a novel scaffold

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• synthesis of tripeptides incorporating new fluorinated heterocyclic hydrazino acids, based on the tetrahydropyridazine scaffold is described. Starting from simple fluorinated hydrazones, these non-proteinogenic cyclic β-amino acids were easily prepared by a zinc-catalyzed aza-Barbier reaction followed by an

• intramolecular Michael addition. Preliminary conformational studies on tripeptides including this scaffold in the central position show an extended conformation in solution (NMR) and in the solid state (X-ray). Keywords: fluoroalkyl groups; heterocycles; hydrazino acids; peptides; tetrahydropyridazines

• tetrahydropyridazine scaffold is also found in numerous natural linear or cyclic peptides such as svetamycins or antrimycins as dehydropiperazic acid (Figure 2) [10]. Whereas many publications have been devoted to the synthesis and structure of piperazic acid derivatives (dehydro, chloro, hydroxy, …) [11][12], nothing

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

• quinazolinone scaffold. They have obtained new benzochromenopyrimidinones, abbreviated as BCPOs, whose synthesis has been accomplished in two steps. First, a microwave-assisted reaction of ethyl cyanoacetate, selected aromatic aldehydes, and 2-naphthol was performed. The second step was the condensation of the

• oxazepane scaffold 11 (Scheme 11). Replacing the nitrogen in the bioactive lactam 11 (γ-secretase inhibitor in AD therapy) with an oxygen should reduce the hydrogen bond donating (HBD) ability of the compounds. The method employs readily available starting materials, resulting in the desired compounds in a

• single step. The oxazepine scaffold can be easily accessed using the Ugi four-component reaction. By modifying this scaffold, the researchers aimed to reduce the hydrogen-bond donating properties. The Passerini reaction, employing bifunctional salicylaldehydes and isocyanides successfully yielded

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

• phenomenon is quite sensitive to changes in the fluorinated sulfur reagent scaffold (see Supporting Information File 1 for more details). This second instance of controlled oligomerization of 1 using CF3SF4Cl was also studied at the PWPB95-D4/def2-QZVPP//PCM(Et2O)-ωB97X-D/def2-TZVP level of theory (Figure 3

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• representative studies include antibacterial, anti-inflammatory, antioxidant, selective inhibitor of COX-2 [34], and anti-HIV activity [35]. In this context, even though indole is considered a privileged scaffold present in some anticancer agents [36], a few examples of methanesulfonylindoles are studied as

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

• studies, because translating their modular biosynthetic logic into a chemical synthetic scheme is rather straightforward [86]. Aside from constructing the core molecular scaffold of these natural products, further modifications may be installed either before or after the assembly of the amino acid or

Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• (small-molecule concept) offer a distinctive advantage in the synthesis of new biologically active molecules, as they are synthetic bioisosters of purine bases. Imidazo[1,2-a]pyrimidine derivatives exhibit a wide range of pharmacological properties [4][5][6]. For example, this scaffold is a key

Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• -indolenines, specially the spiro-heterocyclic indolenines, can be considered as a privileged scaffold, present in several natural products with interesting biological activities, as depicted in Figure 1 [4][5][6][7]. Among the known methods of synthesizing spiro-heterocyclic indolenines, the dearomative

Synthesis of benzo[f]quinazoline-1,3(2H,4H)-diones

• Ruben Manuel Figueira de Abreu,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2708–2719, doi:10.3762/bjoc.20.228

• various functional groups. The optical properties of as-prepared derivatives were investigated by steady-state absorption and photoluminescence spectroscopy. The photophysical properties are strongly altered by the presence N,N-dimethylaniline functional groups on the scaffold, which leads to strongly

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• imidazolium ring formation. The resulting carbene was metalated at the C2 position with Au(I), Cu(I), and Ir(I), obtaining an L-shaped NHC ligand scaffold. Līpiņš et al. introduced a new method for synthesizing 4-azido-6,7-dimethoxy-2-alkyl/arylsulfonylquinazolines, which are key intermediates in the

• reported that imidazole analogs behaved differently due to the ʟ-histidine unit representing a nonphenyl scaffold. Some important data on the bioisosteric modifications of 2-phenethylamine derivatives, focusing on their affinity and core aromatic diversity, were included. In another Review article

Photoluminescence color-tuning with polymer-dispersed fluorescent films containing two fluorinated diphenylacetylene-type fluorophores

• Kazuki Kobayashi,
• Shigeyuki Yamada,
• Motohiro Yasui and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2682–2690, doi:10.3762/bjoc.20.225

• structure (Figure 1a) [14][15][16]. Our extensive efforts have revealed that introducing electron-donating alkoxy and electron-withdrawing cyano groups at both ends of the diphenylacetylene scaffold slows the internal conversion to the πσ* excited state. Further incorporating four fluoro substituents in the

Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

• strategically modifying LB substituents to induce asymmetry, a stereoselective catalytic scaffold was developed, favouring one enantiomer from both epoxide enantiomers. This work advances the in silico design of FLPs, highlighting their potential as asymmetric CCU catalysts with implications for optimising

• K) suggest a kinetically controlled reaction. To further shift the chemical equilibrium toward CO2 capture, increasing steric hindrance at the epoxide was explored by introducing bulky substituents into the scaffold. This resulted in an increase in activation barriers for adduct formation. Including

• plot analysis reveals that the best candidate is F3_NB_C5_CF3, which is the catalyst based on the 2-borylbenzenamine scaffold, with a pyrrolidine substituent on the nitrogen atom and CF3 substituents on the boron. Through strategic modification of the Lewis base substituents, a stereoselective catalyst

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

•  1), are recognized as a “privileged scaffold” in bioorganic and medicinal chemistry [1]. On the other hand, the 2-anilinoquinazolines have been less studied but our groups have developed recently the synthesis of new molecules of this family and discovered a compound (DB18) with a potent inhibition

• ) exhibited a relatively broad cytotoxicity on four cancer cell lines among the seven assayed. On the other hand, two others (4f and 4h) were active only on Caco-2, while another one (4d) only on HCT-116. Thus, the results obtained with these compounds indicate that such a novel heterocyclic scaffold, which

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• variants. A) Access of clavam derivatives by intramolecular photoredox reaction of alkenes. B) Clavulanic acid and its derivatives. C) Construction of the oxacepham scaffold by radical cyclization. Tentative mechanism for the photo-cyclization reaction. Preparation of alkenyl β-lactam derivatives for the

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

• various diseases [17][18][19][20]. Therefore, due to their NO-releasing abilities, furoxan derivatives also demonstrate anticancer, antiplatelet, antiviral and antiparasitic properties [21][22][23][24][25][26][27][28][29][30][31][32]. Another valuable nitrogen heterocyclic scaffold in medicinal chemistry

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

• might be to obtain the pathologically relevant protein targets or off-targets, this may further lead to optimization of the NP scaffold to improve the desired activity. In this review, we focus on the most frequently used chemical proteomic strategies that necessitate a covalent bond between a target

• -crosslinker, is attached synthetically to the basic scaffold (Figure 2A) [28][29][30][31][32]. However, this requires a structure–activity relationship (SAR) screening to ensure that the selected NP retains biological activity after modification. The term probe is further used to unite such NPs and active

• conjugate(s) and the desired analytical output with the information about the protein and conjugate identity. Thus, the linkers have not only the function to simply connect the probe scaffold with an affinity or reporter tag, but they carry previously underappreciated features enhancing the capabilities of

Novel truxene-based dipyrromethanes (DPMs): synthesis, spectroscopic characterization and photophysical properties

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2024, 20, 2163–2170, doi:10.3762/bjoc.20.186

• for diverse applications in future studies. Keywords: condensation; co-timerization; dipyrromethane; Friedel–Crafts acylation; heterocycles; pyrrole; truxene; Introduction The scaffold of truxene (10,15‐dihydro‐5H‐diindeno[1,2‐a;1′,2′‐c]fluorene) and its congeners comprises three fluorene subunits

• -planar having π‐conjugation [2][3][4]. Remarkably, these unique characteristics of the truxene scaffold, results in strong π–π stacking ability in addition to the strong electron‐donating capability – hinting for the truxene’s capability as a worthy building block in the advancement of cutting-edge

• , that is the isotruxene scaffold [30] – having differences in clipping of fluorene moieties, chemists began to synthesize the heteroatom-doped truxenes as well as isotruxene molecules, so-called “hetero-truxenes/isotruxenes” [31][32][33]. As can be inspected from the scientific literature, to date a

Finding the most potent compounds using active learning on molecular pairs

• Zachary Fralish and
• Daniel Reker

Beilstein J. Org. Chem. 2024, 20, 2152–2162, doi:10.3762/bjoc.20.185

• exhibit poor performance during early project stages where the training data is limited and model exploitation might lead to analog identification with limited scaffold diversity. Here, we present ActiveDelta, an adaptive approach that leverages paired molecular representations to predict improvements

• , model exploitation can lead to analog identification, which can limit the acquired knowledge and the scaffold diversity of selected hits [1]. We previously showed that leveraging pairwise molecular representations as training data can support molecular optimization by directly training on and predicting

• networks even when combinatorially expanding datasets through pairing. Chemical diversity in molecular selection Beyond their ability to identify the most potent inhibitors, we sought to determine how these approaches sampled chemical space. When analyzing the scaffold diversity of hits (i.e., the number

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

• yields the sequential addition products 9 in moderate to excellent yields (Scheme 5) [33]. The product can be used as a precursor for the carbapenem scaffold, one of the basic scaffolds of antibiotics. Thermal or photoirradiated decomposition of organotellurium compounds generates carbon radicals that

From perfluoroalkyl aryl sulfoxides to ortho thioethers

• Yang Li,
• Guillaume Dagousset,
• Emmanuel Magnier and
• Bruce Pégot

Beilstein J. Org. Chem. 2024, 20, 2108–2113, doi:10.3762/bjoc.20.181

• , sigmatropic rearrangements have established themselves as robust and versatile tools for many transformations in organic synthesis [1][2][3]. They were widely employed with a wide range of substrates. With a peculiar type of scaffold, S-perfluoroalkyl aryl sulfoxides, in 2009, we were the first to demonstrate