Sequential two-step, one-pot microwave-assisted Urech synthesis of 5-monosubstituted hydantoins from L-amino acids in water

• Wei-Jin Chang,
• Sook Yee Liew,
• Thomas Kurz and
• Siow-Ping Tan

Beilstein J. Org. Chem. 2025, 21, 596–600, doi:10.3762/bjoc.21.46

• accessibility of these bioactive compounds for pharmaceutical applications. Keywords: amino acids; hydantoin; microwave-assisted; one-pot reaction; Urech synthesis; Introduction The hydantoin moiety is a scaffold found in many biologically active compounds exhibiting a diverse range of properties, including

Synthesis, characterization, antimicrobial, cytotoxic and carbonic anhydrase inhibition activities of multifunctional pyrazolo-1,2-benzothiazine acetamides

• Ayesha Saeed,
• Shahana Ehsan,
• Muhammad Zia-ur-Rehman,
• Erin M. Marshall,
• Sandra Loesgen,
• Abdus Saleem,
• Simone Giovannuzzi and
• Claudiu T. Supuran

Beilstein J. Org. Chem. 2025, 21, 348–357, doi:10.3762/bjoc.21.25

• microbroth single-dose assays. Dimethyl sulfoxide was used at a final concentration of 0.1% as negative control. Microbroth dilution assays [52] for the most potent bioactive compounds 7b and 7h were performed using nine serial dilutions of the tested compounds with final concentrations of 256, 128, 64, 32

Antibiofilm and cytotoxic metabolites from the entomopathogenic fungus Samsoniella aurantia

• Rita Toshe,
• Syeda J. Khalid,
• Blondelle Matio Kemkuignou,
• Esteban Charria-Girón,
• Paul Eckhardt,
• Birthe Sandargo,
• Kunlapat Nuchthien,
• J. Jennifer Luangsa-ard,
• Till Opatz,
• Hedda Schrey,
• Sherif S. Ebada and
• Marc Stadler

Beilstein J. Org. Chem. 2025, 21, 327–339, doi:10.3762/bjoc.21.23

• anticancer properties [6]. With concerns about biofilm formation and resistance escalating in the medical field, entomopathogenic fungi have emerged as a promising source of novel bioactive compounds [5]. Our recent exploration of B. neobassiana highlighted this growing interest, affording one tetramic acid

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• oxide by direct UV light absorption. However, this method, although simpler, is not suitable for the present medicinal application. The space and time-controlled release of bioactive compounds is an important tool in bio- and medicinal chemistry to study biochemical mechanisms or to develop new

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• as a vital pharmacophore in medicinal chemistry due to its special biological activity [11][12][13]. In particular, the tricyclic benzimidazole skeleton is ubiquitous in many bioactive compounds and therapeutic agents (Figure 1b) [14][15][16]. Recent studies have shown that fluorinated benzimidazole

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

• of aliphatic and aromatic substituents (Scheme 4). Pyrimidines and pyrimidone-bearing indole derivatives are crucial in organic chemistry because of their extensive use as bioactive compounds with a wide array of significant biological activities (DB03074, DB03304, DB08131) [70][71][72]. In a similar

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

• enantioenriched nitrile products 89 and a reduced Cu(I) complex 94, which is reoxidized through anodic oxidation. The 1,2-diamine moiety is present in numerous natural products and bioactive compounds. In 2022, Xu et al. reported the Cu-catalyzed electrocatalytic diazidation of olefins with ppm-level catalyst

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• reactivity with in situ-generated sulfenate anions, from β-sulfinyl esters, to achieve S–N bond formation. The importance of establishing this S–N bond results from the widespread presence of sulfonyl-containing bioactive compounds, such as the sulfonamide group which can be found in many pharmaceuticals

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

• heterocycles. Example bioactive compounds containing cyclic scaffolds potentially accessible by HVI chemistry. A general mechanism for HVI-mediated endo- or exo-halocyclisation. Metal-free synthesis of β-fluorinated piperidines 6. Ts = tosyl. Intramolecular aminofluorination of unactivated alkenes with a

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

• highly bioactive compounds that can be converted into drug candidates in a fast and efficient manner containing these moieties is the molecular hybridization [8][9][10]. It consists of covalently joining of two or more pharmacophoric fragments to provide new hybrid compounds with improved efficacy and

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

• through the formation of novel reactive intermediates [15][16][17][18]. Fluorine-containing functional groups are essential structural motifs in the development of new bioactive compounds and functional materials. Compared to their non-fluorinated analogs, the presence of fluorine atoms in molecular

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

• construction of spirocyclic motifs is often associated with increased synthetic effort and number of synthetic steps. Hence, developing efficient strategies to access spirocyclic targets with structural diversity is highly desirable and valuable. Among the bioactive compounds containing spiro atoms, the spiro

Efficient modification of peroxydisulfate oxidation reactions of nitrogen-containing heterocycles 6-methyluracil and pyridine

• Alfiya R. Gimadieva,
• Yuliya Z. Khazimullina,
• Aigiza A. Gilimkhanova and
• Akhat G. Mustafin

Beilstein J. Org. Chem. 2024, 20, 2599–2607, doi:10.3762/bjoc.20.219

• useful. 5-Hydroxy-6-methyluracil (HMU) (Figure 1a) and 5-hydroxy-1,3,6-trimethyluracil (HTMU) (Figure 1b) have been identified as effective antioxidants and radical traps [5][6][7]. Additionally, 2-hydroxypyridine (HPy) has significant synthetic potential in the design of various bioactive compounds

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

• electrochemical transformations. Detailed reaction conditions, such as electrolyte, electrode material, and the use of constant current or constant voltage, are presented. Additionally, we discuss the mechanisms of some representative reactions and provide selected examples of LSF of relevant bioactive compounds

• bioactive compounds such as caffeine and prothioconazole (Scheme 2a). Additionally, Lin, Terrett and Neurock's group [8] reported the electrochemical C(sp3)–H methylation of complex molecules. This strategy enabled the synthesis of the "magic methyl" product, a TRPA1 antagonist (Scheme 2b). C–H bond

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

• research [11][12], particularly focusing on innovative approaches to synthesize natural or bioactive compounds [13]. In the carboamination of alkenes, amides are used in photoredox cyclizations under proton-coupled electron transfer (PCET) conditions [14][15][16][17]. An alternative method to generate N

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

• human physiology [30][31]. Moreover, several selenylated molecules have found applications in various fields such as materials or bioactive compounds [32][33][34][35][36][37][38][39][40][41][42][43]. Some selenylated compounds exhibit fascinating biological properties. Despite these separate converging

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

• physiological conditions. Moreover, the target bicyclic compounds were shown to be thermostable substances and could be used in various fields of materials science. Examples of bioactive compounds containing the 1,2,3-triazin-4-one core. The X-ray structure of compound 1b (CCDC 2363621) and 7h (CCDC 2363622

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

• ). This reaction is believed to be one of the most famous MCRs with >2000 papers published in the last 20 years (according to Scopus database). These MCRs allow the direct synthesis of known DHMP drugs such as monastrol, piperastrol, enastron, fluorastrol etc. (Scheme 1B) and dozens of highly bioactive

• compounds with anticancer, antihypertensive, antiinflammatory, antioxidant, antimicrobial, antifungal, antimalarial, antitubercular, antidiabetic, antifilarial, anti-Alzheimer, antiepileptics and other activities [1][2][3][4][5][6][7][8][9][10][11]. The concept of "privileged structures" in medicinal

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

• heterocycles with interesting biological and medicinal properties. Indazole, also called benzpyrazole, is a heterocyclic organic compound commonly found as a structural motif in natural products, pharmaceuticals, agrochemicals, and bioactive compounds [1][2][3][4][5][6]. Indazole-containing compounds possess a

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

• comparable to the original [1]. The main purpose of this approach is quality improvement, such as activity, selectivity, bioavailability, metabolism, and/or toxicity, while expanding the chemical space surrounding bioactive compounds [2][3]. Benzene-to-heteroaromatic ring replacement represents a classical

• bioactive compounds towards different disease-related receptors, as it was described in our previous work [5]. By means of benzene ring aromatic rescaffolding, it is possible to access the 2‑heteroarylethylamine neighboring space. This satellite chemical region is rich not only in structures displaying

• outline which structural motifs are included in this work and which ones are discarded (Scheme 1). In detail, this review encompasses bioactive compounds which satisfy: flexible, open chain-substituted 5/6-membered heteroaromatic scaffolds with decorations, condensed heteroaromatic or polycyclic systems

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

• get 43 in an overall yield of 40–80% (Scheme 17). In this study, 14 distinct products were obtained, and the only limitation was observed using aliphatic aldehydes, due to the instability of the deprotected GBB adducts. Imidazopirimidines are a privileged scaffold incorporated in many bioactive

• compounds. Dömling et al. [50] also reported the synthesis of N-edited guanine derivatives. Different drugs display the guanine motif, fundamental for its biological activity is a triad HBA–HBD–HBD (HBA = hydrogen bond acceptor, HBD = hydrogen bond donor) included in its structure. The authors propose a one

Harnessing unprotected deactivated amines and arylglyoxals in the Ugi reaction for the synthesis of fused complex nitrogen heterocycles

• Javier Gómez-Ayuso,
• Pablo Pertejo,
• Tomás Hermosilla,
• Israel Carreira-Barral,
• Roberto Quesada and
• María García-Valverde

Beilstein J. Org. Chem. 2024, 20, 1758–1766, doi:10.3762/bjoc.20.154

• drugs highlighting their importance in the discovery of novel bioactive compounds. However, their synthesis often faces challenges, including complex functionalization and lengthy reaction sequences. Multicomponent reactions, notably the Ugi reaction, have emerged as powerful tools to address these

• search of new bioactive compounds, as evidenced by the fact that they are present in many marketed drugs [1][2]. These substructures are found fused with other heterocycles in many cases, as illustrated by the antineoplastic dibromophakellstatin [3][4][5][6], the CDK inhibitor trilaciclib [7] or the

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• . Remarkably, data indicate that at least 85% of all bioactive compounds incorporate a heterocyclic moiety into their structure [1][2]. Similarly, steroids are important structures due to their involvement in numerous therapeutic targets across various organisms. The significance of generating heterocyclic

• -ones (spirocarbamates). These spiro heterocycles are commonly obtained in good yields through treatment with triphosgene and DIPEA. In the last decade, Poirier’s group reported a synthetic strategy to produce several spiro derivatives as discovery platforms for new bioactive compounds (Scheme 20) [39

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

• other bioactive compounds. By providing an overview of the various methylation options available, this review is intended to emphasise the biocatalytic potential of RiPP methyltransferases and their impact on the field of natural product chemistry. Keywords: biocatalysis; methylation; post

• varying acceptor regions to demonstrate the broad range of methylated positions in ribosomally synthesised peptides (Figure 1). This article also highlights the potential application of RiPP MTs in biocatalysis and their ability to enable the production of bioactive compounds with tailored chemical

Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• ; quinoline; Introduction Nitrogen-containing molecules are important bioactive compounds and intermediates in chemical synthesis. Therefore, the chemical transformations of nitrogen-containing compounds have been widely studied in the field of organic synthesis [1][2][3][4]. For instance, the reduction of