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

• ], antioxidant [34], cytotoxic [35], and antiproliferative [36]. The structures of these compounds allow the synthesis of a large collection of bioactive molecules due to their nucleophilic and electrophilic properties [37]. One of the forms of modifications is at the methylene group, particularly in the 5

Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• para-selectivity observed in Friedel–Crafts acylation. The authors anticipate expanding this strategy to other reaction processes, allowing the efficient development of transformative synthetic methods, constructing new chemical spaces for drug discovery, and modifying bioactive molecules (Scheme 13

• mild conditions, using sustainable methods with low-cost materials, and using non-toxic reagents. Its proven potential includes medicinal chemistry, pharmaceuticals, materials science, and the late-stage functionalization of complex bioactive molecules. Recent synthetic advances in methodology

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

• wide range of applications ranging from materials [1][2] to bioactive molecules [3][4]. Phenanthridine [5][6], naphthyridine [7][8][9], and phenanthroline [10] ring structures have each been studied for such potential uses (Figure 1). While reported analogs within this class of molecules are numerous

• counterparts 13–18. Because fused ring heterocycles are common components of bioactive molecules, a preliminary evaluation of toxicity for this newly defined class of compounds was completed. Antimicrobial potency against Gram-positive bacteria Bacillus subtilis and Staphylococcus epidermidis, Gram-negative

An Fe(II)-catalyzed synthesis of spiro[indoline-3,2'-pyrrolidine] derivatives

• Elizaveta V. Gradova,
• Nikita A. Ozhegov,
• Roman O. Shcherbakov,
• Alexander G. Tkachenko,
• Larisa Y. Nesterova,
• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2025, 21, 2383–2388, doi:10.3762/bjoc.21.183

• bioactive molecules (Figure 1). This scaffold exhibits a broad range of pharmacological activities, including significant in vitro antimycobacterial properties [4], potent antitumor effects against melanoma cell lines [5], and antagonism of TH2 lymphocyte function [6]. Due to their wide-ranging biological

Research towards selective inhibition of the CLK3 kinase

• Vinay Kumar Singh,
• Frédéric Justaud,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Blandine Baratte,
• Thomas Robert,
• Stéphane Bach,
• Chada Raji Reddy,
• Nicolas Levoin and
• René L. Grée

Beilstein J. Org. Chem. 2025, 21, 2250–2259, doi:10.3762/bjoc.21.172

• approved drug on the market), Tchem (chemistry, known to bind to small molecules with high potency), Tbio (biology, kinases that have notably gene ontology leaf term annotations associated with disease and cellular role but lack associations with bioactive molecules) to the less explored Tdark (dark genome

Synthesis of triazolo- and tetrazolo-fused 1,4-benzodiazepines via one-pot Ugi–azide and Cu-free click reactions

• Xiaoming Ma,
• Zijie Gao,
• Jiawei Niu,
• Wentao Shao,
• Shenghu Yan,
• Sai Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 2202–2210, doi:10.3762/bjoc.21.167

• 7a–k in 36–90% yields, 8a–g in 77–92% yields. Note: When 2-yn-1-amine hydrochlorides 2b–e were employed in this one-pot reaction, Et3N (0.3 mol, 1.5 equiv) was added into the vessel at the initial stage. Some bioactive molecules bearing triazole, tetrazole, and 1,4-benzodiazepin rings. 1H NMR spectra

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• , this protocol was an efficient and sustainable approach to synthesize 2,3′-biindolyl atropisomers and could be potentially applied in manufacture of functional materials, bioactive molecules and chiral ligands. Construction of isoindolinones and indolizines An electrochemical and copper-catalyzed

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• versatile scaffold for bioactive molecules) with up to 99% yield and 96% ee were prepared (Scheme 69). The large electron-donating groups of 3,5-di-tert-butyl-4-methoxyphenyl (DTBM) improved the activities of the CuI–thiophene-2-carboxylate catalyst (CuTc) while the use of (R)-DTBM-GarPhos as the chiral

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• powerful routes to the asymmetric total synthesis of these bioactive molecules. The precursors of the key bioinspired transformations 36, 38 and 40 were efficiently synthesized from simple fragments aryl aldehyde 42 or 43, phenylboronic acid 44 and chiral auxiliary-containing building block 45, through

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• isolated from organisms are often asymmetric in their spatial structures, and these unique spatial structures are precisely what lead to their diverse biological activities [1][2][3][4]. For the synthesis of these natural products or bioactive molecules, chemists usually need to consider how to carry out

• emphasis on the desymmetrization of diols. Prochiral 1,3-diols, as simple and practical substrates, have been widely used in developed desymmetrization methodologies with applications in the total synthesis of natural products and bioactive molecules, including enzymatic acylation, transition-metal

N-Salicyl-amino acid derivatives with antiparasitic activity from Pseudomonas sp. UIAU-6B

• Joy E. Rajakulendran,
• Emmanuel Tope Oluwabusola,
• Michela Cerone,
• Terry K. Smith,
• Olusoji O. Adebisi,
• Adefolalu Adedotun,
• Gagan Preet,
• Sylvia Soldatou,
• Hai Deng,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2025, 21, 1388–1396, doi:10.3762/bjoc.21.103

• compounds 2 and 5 showed modest anti-L. major activity, while all other compounds displayed no activity. This study shows the Pseudomonas strain as a reservoir of untapped secondary metabolites and as a potential source for isolating unique bioactive molecules. Experimental General experimental procedures

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

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• compatibility with primary, secondary, and tertiary bromides, yielding benzo-fused lactams with good functional group tolerance, thereby highlighting the method’s versatility for the synthesis of diverse bioactive molecules. The proposed mechanism involves the initial generation of alkyl radical 69 from α

Chitosan-supported CuI-catalyzed cascade reaction of 2-halobenzoic acids and amidines for the synthesis of quinazolinones

• Xuhong Zhao,
• Weishuang Li,
• Mengli Yang,
• Bojie Li,
• Yaoyao Zhang,
• Lizhen Huang and
• Lei Zhu

Beilstein J. Org. Chem. 2025, 21, 839–844, doi:10.3762/bjoc.21.67

• catalytic efficiency (up to 99% yield). Keywords: chitosan-supported CuI catalyst; cyclization reaction; mild conditions; quinazolinone; Introduction Quinazolinones are not only a key core of nitrogen-containing benzo heterocyclic compounds found in many natural products and bioactive molecules [1][2][3

Copper-catalyzed domino cyclization of anilines and cyclobutanone oxime: a scalable and versatile route to spirotetrahydroquinoline derivatives

• Qingqing Jiang,
• Xinyi Lei,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2025, 21, 749–754, doi:10.3762/bjoc.21.58

• pivotal structural elements in drug discovery [1][2][3][4]. Notably, tetrahydroquinoline derivatives featuring a strain-inducing ring system are prevalent in numerous bioactive molecules, including those with promising therapeutic potential for neurological disorders, oncology, and various other medical

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

• motif has been exploited in the design of bioactive molecules [22][23] such as the histone deacetylase (HDAC) inhibitors 6 and 7 (Figure 2). The presence of the 1,2-difluoro moiety in 6 leads to greater potency and selectivity for certain HDAC isoforms, attributable to the higher polarity of the

• cyclic amines. Next, we will examine some important derivatives of amines, such as amides and sulfonamides. Throughout, the emphasis will mostly be on bioactive molecules, but finally this section will conclude by examining a different type of molecular function, namely, organocatalysis. When fluorine is

• case (e.g., 107), suggesting that the NH···F interaction (i.e., II, Figure 12) is not a dominant one. The gauche preference of β-fluoroamides has been exploited to control the conformations of a variety of bioactive molecules [186]. For example, the activity of the GPR119 receptor agonist 108 (Figure

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• cyanation of benzylic C(sp3)–H bonds (Figure 7) [56]. A wide range of electron-poor and electron-rich alkylarenes 20 are suitable substrates for this electrophotocatalytic radical relay strategy. Additionally, late-stage functionalization of bioactive molecules provides the corresponding chiral cyanation

Intramolecular C–H arylation of pyridine derivatives with a palladium catalyst for the synthesis of multiply fused heteroaromatic compounds

• Yuki Nakanishi,
• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2024, 20, 3256–3262, doi:10.3762/bjoc.20.269

• palladium catalyzed C–H arylation to pyridine derivatives. The cyclization reaction proceeded in a moderate to excellent yield when an appropriate phosphine ligand was employed. The reaction is expected to be useful for the synthesis of functional materials, and bioactive molecules in a facile manner

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

• , the tetrahydropyridazines, six-atom nitrogenous heterocycles, are found in various bioactive molecules such as influenza virus neuraminidase inhibitors, GABA type A receptor modulators, and regulators of progesterone receptor or cannabinoid CB1 receptor antagonists (Figure 1) [6][7][8][9]. This

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

• research. Key to chemical structure metagenomics is the ability to predict the structure of a natural product based on its biosynthetic gene sequences, which facilitated the discovery of numerous new bioactive molecules and helped uncover oversampled/underexplored niches of decades of BGF based discovery

• approaches have already facilitated the discovery of numerous new bioactive molecules [29][30][31][32][33][34][35][36] and shed light on the scope of past discovery efforts by uncovering select oversampled/underexplored niches in the natural product chemical spaces [37]. While nonribosomal peptides (NRP

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

• scaffolds for bioactive molecules. Thus, it appeared interesting to explore novel molecules with extended aromatic units around this basic quinazoline core and our first choice was N-arylbenzo[h]quinazoline-2-amines with the general structure C as indicated in Figure 1. Very limited studies have been

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

• . For example, Liu and colleagues demonstrated the electrochemical oxidation of benzylic C–H bonds to ketones using tert-butyl hydroperoxide as the radical initiator [14]. This method was applied to functionalize bioactive molecules, with celestolide, ibuprofen methyl ester, and papaverine being

• leads to an intermediate product, which is then deprotonated, generating the thiol radical. This allowed for the preparation of the para-thiolation product (Scheme 11). Sulfonamides are an important class of bioactive molecules. In 2021, the Waldvogel group disclosed the first C(sp2)–H functionalization

• cathodic reduction and to prevent the reoxidation of the reduced SO2 at the anode, a divided cell setup is required (Scheme 12). C–H bond halogenation: Aryl and alkyl halides are important synthetic building blocks for cross-coupling reactions as well as bioactive molecules with applications in

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• 85%), compatible with many functional groups, and allows to synthesize a series of difficult-to-access meta-substituted anilines of interest for medicinal and material chemistry. The meta-hetarylaniline motif in bioactive molecules. The model series of synthesized 1,3-diketones and corresponding

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• (s, 3H); 13C{1H} NMR (75 MHz, DMSO-d6) δ 159.4, 144.7, 129.3, 123.6, 123.2, 122.8, 120.0, 118.0, 64.2, 52.2, 41.4, 14.4, 13.9; IR (KBr disk): 1708, 1459, 1442, 1392, 1326, 1252, 1196 cm−1; HRESIMS (m/z): [M + H]+ calcd for C10H10BrN2O2+, 268.9921; found, 268.9918. Indazole-containing bioactive

• molecules. Tautomerism of indazole. DFT-calculated deprotonation of 6 with Cs2CO3 in implicit THF with the temperature of the calculation set to 90 °C to simulate the dioxane conditions (top) and energy differences of four enolate resonance structures of 6 calculated as discrete structures. The hybrid is

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• driven largely by the beneficial effects of including fluorine into bioactive molecules. These advantages include the modulation of potency, bioavailability and physical properties of drug and agrochemical compounds [1][2][3]. The significance of fluorination is reflected in the fact that a large number

• the relative stability of primary, secondary and tertiary benzylic radicals and cations. As a result, the presence of benzylic C(sp3)–H bonds in bioactive molecules can be problematic as they are particularly labile to enzymatic oxidation [16], and hence, their functionalisation has become a strategy

• , including bioactive molecules, was detailed in their work. Similar to the Doyle report, excess C–H substrate (up to 3 equivalents with respect to HAT reagent) was required in many cases, with the exception of tertiary benzylic substrates, which required only 1 equivalent of substrate and 2 equivalents of