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

• ]. In addition, carbonyldiimidazole-based heteroannulations via MCRs have been reported, giving access to drug like scaffolds [21][22][23][24]. However, their employment in C1 chemistry should and could be advanced. Herein, we point out formamide as an alternative relevant building block for C1

• be established as a C1 feedstock. [25]. Its high polarity and dielectric constant (it is miscible with water) [26], with the ability to solubilize a wide range of reagents, from salts to polymers, proteins and saccharides, renders formamide an excellent C1 building block [25][27]. Thus, our target

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

• additive. Some control experiments support a mechanism whose key intermediates are the formation of the iminium ion XIX, originated from aniline with formaldehyde which serves as the C1 building block, and the generation of the cyclic α,β-unsaturated ethers XX by Cu(OTf)2-catalyzed dehydrogenation of the

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

• carboxylic building block. The obtained molecules were evaluated for their ability to inhibit β-amyloid aggregation by the interaction with two β‐amyloid peptides, Aβ1‐42 and AβpE3‐42. The aggregation inhibition experiment, which measures the decrease of fluorescence, was carried out with the thioflavin T

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

• the application of this reagent as a central building block in the synthesis of hybrid systems via Ugi-azide reactions, including structures based on triazoles-tetrazoles [24][26][27], benzofuran-tetrazoles [23] and indolizines-tetrazoles [25], all of which have significant relevance in medicinal

Tailored charge-neutral self-assembled L₂Zn₂ container for taming oxalate

• David Ocklenburg and
• David Van Craen

Beilstein J. Org. Chem. 2024, 20, 3007–3015, doi:10.3762/bjoc.20.250

• preparation and host assembly. The synthesis adheres to a two-synthon approach which relies on the connection of two building blocks through a CuAAC click reaction (Scheme 1). Building block S1, the azide, is not modified in this work and the preparation is achieved with an overall yield of 43% via the

• previously reported methods. Building block S2, based on dipropargylamine, is synthesized via a Schotten–Baumann reaction with benzoyl chloride, resulting in the flexible dialkyne backbone with a yield of 95%. The functionalization was envisioned to enhance the solubility of the ligand as we usually have

4,6-Diaryl-5,5-difluoro-1,3-dioxanes as chiral dopants for liquid crystal compositions

• Maurice Médebielle,
• Peer Kirsch,
• Jérémy Merad,
• Carolina von Essen,
• Clemens Kühn and
• Andreas Ruhl

Beilstein J. Org. Chem. 2024, 20, 2940–2945, doi:10.3762/bjoc.20.246

• nematic host mixtures Host 1 and Host 2. The extension of the chiral substructure (4 →3) by the liquid crystal building block 1 into a more rod-like shape is further boosting the HTP by roughly a factor of 2. Moreover, the HTP of both compounds 3 and 4 depends strongly on the LC host mixture: for the more

C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• trifluoromethylthiolated molecules, which could be used as synthetic handles for synthesizing more complex molecules, is still appealing. In this context, we turned our attention to the trifluoromethylthiolated hydrazones, an interesting building block. Indeed, aldehyde hydrazones have been well studied and used in

Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

• Yukiko Karuo,
• Keita Hirata,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• chlorine atoms as reported by Hosoya and Niwa et al. In this study, we investigated the synthesis of fluoroalkenes 2 or fluoroenynes 3 by Suzuki–Miyaura or Sonogashira cross-couplings with a key building block 1 (Scheme 1D). Results and Discussion Optimization of the conditions of cross-coupling reactions

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

• oxygen atoms [6][7]. Carbon capture and utilisation (CCU) technologies involve the extraction of CO2 from the atmosphere of the Earth to generate value-added chemicals, which can serve as platform chemicals in other chemical processes [20][21]. This is achieved by inserting CO2 as a C1 building block

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• intramolecular interaction between fluorine and metals would also facilitate the smooth progress of these reactions. Such high potential of 1a allowed us to apply it to nucleophilic epoxidation because the resultant epoxyester 2a is recognized as an intriguing building block (Scheme 1). Another expectation to 2a

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

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

• ]. Verrulactones A–C and E (43–46) are dimeric structures, where verrulactones A and B can be considered as altertenuol (31) dimers, verrulactone C consists of an altertenuol and an alternaone A (123, vide infra) moiety, and verrulactone E contains an altertenuol and a dehydroaltenusin (74, vide infra) building

• block (Figure 12). The verrulactones were isolated from Penicillium verruculosum [187][193][221] and verrulactone A and B were further isolated from Alternaria alternata [159][160]. Constitution and relative configuration of these compounds was determined by NMR-spectroscopic methods, where the

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

• -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

• the importance of DPMs in mind due to their utmost significance as a building block in the construction of porphyrinogens, related polypyrrolic macrocycles, and pigments [39][40][41]. As shown in Figure 1, these DPMs and many more have fruitfully been used by several research groups in sensing/binding

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• bacterial sugars, the parametrisation of each building block is needed and requires the use of ab initio methodologies, including several steps of charges and electron density calculations, optimization and minimization, making the computational study of bacterial glycans difficult and time-consuming. 2

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• organic synthesis. For instance, hydrazinecarbothioamide (40) can be used to synthesize bisheterocycles. Mohamed et al. were able to combine Hantzsch thiazole and Knorr pyrazole synthesis with this building block. Thiazolyl-pyrazolyl-chromenes 43 were synthesized in good yields from substituted 3

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• the critical role of in situ-generated molecular iodine (Scheme 8) [44]. Formal cycloaddition Hydrazones constitute a versatile building block for the construction of azacycles through formal cycloaddition reactions. Under oxidative electrochemical conditions, either the oxidation of the hydrazone or

• reactivity profile of hydrazones, the electrooxidative transformations of such a molecular building block provides a fascinating route to valuable compounds under mild and safe reaction conditions. Alone, the electrooxidation of NH-aryl, -tosyl, and -acylhydrazones triggered the cyclization of a radical

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

Hetero-polycyclic aromatic systems: A data-driven investigation of structure–property relationships

• Sabyasachi Chakraborty,
• Eduardo Mayo Yanes and
• Renana Gershoni-Poranne

Beilstein J. Org. Chem. 2024, 20, 1817–1830, doi:10.3762/bjoc.20.160

• distribution of the COMPAS-1 molecules (light blue) is contained within the distribution of the COMPAS-2 molecules (purple). In other words, the expansion of the building block library widens the property distributions towards both higher and lower energies, providing access to functional molecules with

• of building block affects the properties, and whether these effects are due solely to the presence of the heteroatoms or to the aromatic nature of heterocycles are among the questions we aim to answer in the subsequent sections. Influence of global structural features In this section, we investigate

• antiaromatic building blocks are boron-containing rings (borole, 1,4-dihydro-1,4-diborinine). Thus, it is not clear whether these trends are due to the identity of the heteroatom or to the nature of the ring. To answer this question, we investigated the influence of each individual building block. Figure 9A

Synthesis and characterization of 1,2,3,4-naphthalene and anthracene diimides

• Adam D. Bass,
• Daniela Castellanos,
• Xavier A. Calicdan and
• Dennis D. Cao

Beilstein J. Org. Chem. 2024, 20, 1767–1772, doi:10.3762/bjoc.20.155

• periphery of the aromatic core to yield different structural isomers is effective for producing interesting new materials. Ourselves and others have investigated 1,2,3,4-benzene diimide, also known as mellophanic diimide [1], as a building block for heteroacenes [2][3][4][5] and polyimides [6][7][8]. The

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• -serine, which provides the methyl group in this case. Another methyl donor that provides a C1 building block for ʟ-methionine and subsequent SAM synthesis is betaine. Betaine-homocysteine MT remethylates ʟ-homocysteine to ʟ-methionine. Non-SAM-dependent MTs catalyse B12-dependent methylations using the

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction

• Manoel T. Rodrigues Jr.,
• Aline S. B. de Oliveira,
• Ralph C. Gomes,
• Amanda Soares Hirata,
• Lucas A. Zeoly,
• Hugo Santos,
• João Arantes,
• Catarina Sofia Mateus Reis-Silva,
• João Agostinho Machado-Neto,
• Leticia Veras Costa-Lotufo and
• Fernando Coelho

Beilstein J. Org. Chem. 2024, 20, 1167–1178, doi:10.3762/bjoc.20.99

• inhibitory concentration (IC50) of 10 ng/mL, lepistatin A (3), along with two other new chlorinated analogs, that were isolated from Basidiomycete Lepista sordida culture, pauciflorol F (4), isolated from Vatica pauciflora, which is an important building block for the biosynthesis of bioactive polyphenols

Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives

• Tural N. Akhmedov,
• Ajeet Kumar,
• Daken J. Starkenburg,
• Kyle J. Chesney,
• Khalil A. Abboud,
• Novruz G. Akhmedov,
• Jiangeng Xue and
• Ronald K. Castellano

Beilstein J. Org. Chem. 2024, 20, 1037–1052, doi:10.3762/bjoc.20.92

• 13. The solvent 1,4-dioxane is crucial to the synthesis and purification in the initial two steps as other solvents such as THF make the purification process more intricate. This sequence is followed by SNAr with ammonia (29% v/v) to obtain building block diaminopyrazine 12. The synthesis of

• Yamashita’s DCPQs 1a (BenzCN) and 2a (XyICN) began via SNAr reaction of commercially available o-phenylenediamines 11a and 11b with building block 13 to afford dihydropyrazine derivatives 8 and 9, respectively, as precipitates in 1,4-dioxane solution. The reaction generates two equivalents of HCl, adding a

• modified procedure from the literature was implemented [28]. To synthesize 6a, the condensation was performed with 9,10-phenanthrenequinone, building block 12 in the presence of glacial CH3COOH, trifluoracetic acid, and 1,4-dioxane at reflux. Then, recrystallization from DMF and sublimation under ambient

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• powerful method for the introduction of a C1 building block into organic substrates using carbon monoxide, its surrogates, or compounds able to act as carbon monoxide sources [11]. In recent years, many groups have used the carbonylation approach for the synthesis and functionalization of indoles, which is

• synthesis of a set of 12 desired products. These included an ethyl ester and a carboxylic acid, and were all obtained in good yields of up to 99% (Scheme 45). Conclusion We have summarized the importance of carbon monoxide as C1 building block to promote different kinds of transformations to synthesize and

Innovative synthesis of drug-like molecules using tetrazole as core building blocks

• Jingyao Li,
• Ajay L. Chandgude,
• Qiang Zheng and
• Alexander Dömling

Beilstein J. Org. Chem. 2024, 20, 950–958, doi:10.3762/bjoc.20.85

• ]. In stark contrast, a method for the synthesis of drug-like tetrazole compound libraries involving a building block approach have remained elusive, with success being reported thus far only with the tetrazole amine [14][15]. The use of a tetrazole building block in MCRs would have all the advantages

• due to the protected nature of the tetrazol. Additionally, inclusion of a strategically placed tetrazole and bioisostere replacement of MCR substrate with tetrazole may give rise to molecules with improved drug-like characteristics with nominal weight or size difference. This tetrazole building block

• approach will allow direct access to ready to screen molecular scaffolds for medicinal chemistry programs to investigate different biological activities [16][17][18]. Motivated by the shortcomings of current methodologies and the absence of a tetrazole building block approach, we have pursued and report

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• from both compounds. The first investigation of 1,2-BCPs as an isosteric replacement for ortho-benzene was reported by Baran, Collins and co-workers [26]. They prepared a wide variety of 1,2-BCPs from a common 2-substituted [1.1.1]propellane building block, propellane 3a (Scheme 1A). Propellane 3a was

• methylation of the intermediate diacid. As for the 1,2-cubanes, the authors were able to derivatise this general building block into a range of other 1,3-cubanes via metallophotoredox catalysis using acid 167 and redox active esters 168 and 169 (Scheme 17B) [51]. Arylation (to 170), amination (to 171) and

Skeletal rearrangement of 6,8-dioxabicyclo[3.2.1]octan-4-ols promoted by thionyl chloride or Appel conditions

• Martyn Jevric,
• Julian Klepp,
• Johannes Puschnig,
• Oscar Lamb,
• Christopher J. Sumby and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2024, 20, 823–829, doi:10.3762/bjoc.20.74

• cyrene (2) allows for its use as a chiral solvent [4]. This product is emerging as a promising platform chemical for the construction of chiral small molecules for pharmaceuticals [5][6][7][8], as a building block for catalysts and auxiliaries [9][10][11], and in materials applications [12][13][14]. New