Switchable pathways of multicomponent heterocyclizations of 5-amino-1,2,4-triazoles with salicylaldehydes and pyruvic acid

• Yana I. Sakhno,
• Oleksander V. Buravov,
• Kostyantyn Yu. Yurkov,
• Anastasia Yu. Andryushchenko,
• Svitlana V. Shishkina and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2030–2035, doi:10.3762/bjoc.21.158

• formation of heterocyclic systems in a minimal number of steps and offer several ways to vary substituents and they are widely used in drug discovery and development, as well as in diversity-oriented synthesis [1][2][3][4]. In addition, the application of condition-based divergence strategy [5] and the

• are shown at 50% probability level. Diversity of heterocyclization products from reaction of aminoazoles with salicylaldehydes, and pyruvic acids. MCRs of 3-amino-5-methylthio-1,2,4-triazole (1a) and 3-amino-5-methoxy-1,2,4-triazole (1b) with salicylaldehydes 2a–f, and pyruvic acid (3). MCRs of 3

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• diverse co-substrates. A high-throughput approach was used to identify promising substrate/co-substrate/catalyst combinations which were then prioritised for purification by mass-directed HPLC to yield a total of thirty reactive probes. The structural diversity of the probe set was increased by the

• the discovery of small molecule modifiers for investigating and engineering proteins. Keywords: covalent probes; molecular diversity; rhodium carbenoids; Introduction Diverse sets of reactive probes can facilitate the discovery of chemical tools and drugs that chemically modify protein targets [1][2

• amino acids [8][9][10]. Sets of reactive probes are generally prepared using robust reactions, most usually amide formation, chosen from the toolkit that currently dominates medicinal chemistry [11] which may, in turn, limit probe structural diversity. We have developed a unified connective approach for

Synthesis, biological and electrochemical evaluation of glycidyl esters of phosphorus acids as potential anticancer drugs

• Almaz A. Zagidullin,
• Emil R. Bulatov,
• Mikhail N. Khrizanforov,
• Damir R. Davletshin,
• Elvina M. Gilyazova,
• Ivan A. Strelkov and
• Vasily A. Miluykov

Beilstein J. Org. Chem. 2025, 21, 1909–1916, doi:10.3762/bjoc.21.148

• compounds have garnered considerable attention from both pharmaceutical companies and researchers, reflecting their significance in drug development and therapeutic innovation [5][6][7]. The structural diversity of phosphorus-containing molecules, which includes phosphotriesters, phosphonates, phosphinates

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• potential in the CPA-catalyzed asymmetric synthesis of these unique chiral molecules, some current limitations and challenges still need to be addressed, particularly enhancing the efficiency of the methods and expanding the structural diversity of the products. Firstly, the chiral products generated

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• vesicles, micelles and nanoparticles, overcoming the difficulties in modifying cyclodextrin and cucurbituril. These features make CAs and PAs promising candidates for stimulus responsive drug release systems [46]. Their structural diversity and functional designability offer broad prospects for targeted

• accessibility, structural adaptability, and responsiveness to external stimuli (pH, light, enzyme, hypoxia) facilitate sustained drug release, side effect mitigation, and therapeutic efficacy, making them increasingly prominent in drug carrier research. In recent years, the diversity of supramolecular

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• attention due to its broad applications in various fields, including but not limited to drug discovery, asymmetric catalysis, and materials science (Figure 1b). Consequently, the development of efficient and stereoselective methods for assembling such scaffolds with respect to structural diversity has

• functionality in 63 allowed for versatile derivatizations, such as reduction, reductive amination, condensation, and olefination, which further expanded the structural diversity of the resulting products. Summary and Outlook The past few years have witnessed exciting progress in developing catalytic asymmetric

• catalysis, particularly with palladium and silver, has proven to be highly effective, expanding the scope as well as the activation mode of chiral catalysts could greatly enrich reaction types and accessible structural diversity. Third, further investigation into the potential applications of the resulting

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• papers (three Full Research Papers and two Letters) contributed by scientists from Asia and Europe. The breadth of topics and the geographical diversity of the authors reflect the global interest in copper catalysis today. The Review article by Yang and Fang focuses on copper-catalyzed yne–allylic

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• structures, enhance solubility, and expand functional diversity [6]. Substituting carbon atoms with electron-deficient nitrogen atoms introduces new opportunities to fine-tune redox potentials, charge-transport behavior, and intermolecular interactions [7]. These modifications have proven especially valuable

• applications in chiral optoelectronics. Several comprehensive reviews have examined specific classes of these molecules. Crassous and co-workers provided a detailed overview of heterohelicenes up to 2019, focusing on their structural diversity and functional applications [11]. Nowak-Król and colleagues

• underscore the synthetic versatility and functional diversity of helicene-based systems, spanning electrochromism, thermally activated delayed fluorescence, and circularly polarized luminescence. Such structural innovations provide valuable frameworks for the development of next-generation chiral

Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles

• Vladimir G. Ilkin,
• Pavel S. Silaichev,
• Valeriy O. Filimonov,
• Tetyana V. Beryozkina,
• Margarita D. Likhacheva,
• Pavel A. Slepukhin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104

• analogy with an aza-Michael reaction first with the addition of iminoiodinane accompanied with reorganization of double bonds including attack of the negatively charged sulfur atom on nitrogen with subsequent elimination of iodobenzene as good leaving group. The diversity of the structure of the target

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

• Pseudomonas are huge producers of bioactive natural products with a vast array of structural and functional molecular diversity. This reflects in the bacteria’s genome which ranges in size from 4.6 to 7.1 megabases with 4237 to 6396 predicted genes [1]. Natural products play a major role in the live of these

Selective monoformylation of naphthalene-fused propellanes for methylene-alternating copolymers

• Kenichi Kato,
• Tatsuki Hiroi,
• Seina Okada,
• Shunsuke Ohtani and
• Tomoki Ogoshi

Beilstein J. Org. Chem. 2025, 21, 1183–1191, doi:10.3762/bjoc.21.95

• , Kanazawa, 920-1192, Japan 10.3762/bjoc.21.95 Abstract Development of three-dimensional (3D) building blocks is a key to change tight molecular assemblies of rigid π-conjugated planes into organic functional materials endowed with molecular-size cavities. To increase the diversity of available 3D building

Enhancing chemical synthesis planning: automated quantum mechanics-based regioselectivity prediction for C–H activation with directing groups

• Julius Seumer,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2025, 21, 1171–1182, doi:10.3762/bjoc.21.94

• molecular architectures in pharmaceuticals, polymers, and agrochemicals. Despite advancements in directing group (DG) methodologies and computational approaches, predicting accurate regioselectivity in C–H activation poses significant difficulties due to the diversity and complexity of organic compounds

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• procedures and harsh reaction conditions, resulting in limited substituent and scaffold diversity [18][19]. In this regard, multicomponent reactions (MCRs) have gained increasing attention for their operational simplicity, efficiency, robustness, atom economy, and potential for diversity-oriented synthesis

• ][44] and hydroalkoxylations [45]. In 2013, Van der Eycken and co-workers described an intramolecular cationic gold-catalyzed post-Ugi heteroannulation of imidazoles with activated alkynes for the diversity-oriented synthesis of imidazo[1,4]diazepines 13 from Ugi-derived propargylamides 12 (Scheme 1c

• operational simplicity, the accessibility of starting materials, and a diversity-oriented approach. Results and Discussion First, we prepared a series of acyclic pyrazole-tethered propargylamide precursors 15 via the Ugi four-component reaction (U4CR) of 1H-pyrazole-3-carbaldehydes 14a–d, primary amines 2a–l

Substituent effects in N-acetylated phenylazopyrazole photoswitches

• Radek Tovtik,
• Dennis Marzin,
• Pia Weigel,
• Stefano Crespi and
• Nadja A. Simeth

Beilstein J. Org. Chem. 2025, 21, 830–838, doi:10.3762/bjoc.21.66

• medicine. Despite their potential, their structural diversity is still limited and a larger pool of substitution patterns remains to be systematically investigated. This is paramount as electronic effects play a crucial role in the behavior of photoswitches and a deeper understanding enables their

New advances in asymmetric organocatalysis II

• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 766–769, doi:10.3762/bjoc.21.60

• ]. In 2022, three Review articles and nine research papers showcased the diversity and breadth into which asymmetric organocatalysis had grown. This follow-up thematic issue “New advances in asymmetric organocatalysis II” aims to monitor the progress in this exciting area and highlights excellent

• transformation was catalyzed by a calcium complex of BINOL phosphate [29]. As can be seen from the summary above, the articles in this thematic issue cover a diverse array of topics in contemporary asymmetric organocatalysis. Moreover, they also reflect the diversity of our scientific community, as researchers

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• , including non-toxicity, bench-stability, structural diversity, straightforward preparation, and broad commercial availability. Significant contributions include Sawamura's work with alkyl–9-BBN [32][33][34][35][36][37] as a nucleophile. These developments have collectively transformed copper-catalyzed AAA

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• recent years, multicomponent reactions (MCRs) have become one of the most important synthetic tools coming close to fulfilling the requirements of ideal reactions. They are ideally suited also for the generation of high chemical diversity compounds from simple reagents, either through scaffold

• the MCR product is possible thus increasing the versatility of these reactions in terms of structural diversity and molecular complexity. In this context, a wide variety of heterocycles and macrocycles as important biological scaffolds have been synthesized [6]. One of the most important components

• ] with which a wide range of aromatic and aliphatic disubstituted alkynes were reactive, resulting in a greater diversity of quinolines II. In both cases, regardless of the catalyst used, the MCR tolerates a wide variety of anilines that have either electron-donating or electron-withdrawing groups with

Synthesis of electrophile-tethered preQ₁ analogs for covalent attachment to preQ₁ RNA

• Laurin Flemmich and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 483–489, doi:10.3762/bjoc.21.35

• antibiotic properties, others expand the chemical diversity and thus the functional sophistication of ribonucleic acids, as in the case of Q [3]. In most bacteria, Q biosynthesis is tightly regulated by riboswitches, which are highly structured RNA elements located mostly in the 5’-leader of messenger RNA

New tandem Ugi/intramolecular Diels–Alder reaction based on vinylfuran and 1,3-butadienylfuran derivatives

• Yuriy I. Horak,
• Roman Z. Lytvyn,
• Andrii R. Vakhula,
• Yuriy V. Homza,
• Nazariy T. Pokhodylo and
• Mykola D. Obushak

Beilstein J. Org. Chem. 2025, 21, 444–450, doi:10.3762/bjoc.21.31

• achieving molecular diversity of derivatives for creating libraries of compounds for bioscreening. Finally, in such a tandem Ugi/IMDA reaction, furyl-2-pentadienal was studied. It was found, that the Ugi adduct formed from (2E,4E)-5-(furan-2-yl)penta-2,4-dienal (8) underwent the IMDA reaction, without

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

• highly effective platform for improving reaction efficiencies. These molecules can facilitate single-electron transfer or energy transfer under mild conditions, and their structural diversity allows for fine-tuning of their redox potentials and light absorption characteristics. This adaptability makes

Molecular diversity of the reactions of MBH carbonates of isatins and various nucleophiles

• Zi-Ying Xiao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2025, 21, 286–295, doi:10.3762/bjoc.21.21

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

• convergent chemistry characterized by diversity, complexity and efficiency. MCRs are compatible with C1 chemistry due to the generally great tolerance of different functional groups. They have been mostly employed in the synthesis of oxazolidinones and oxazinanones utilizing CO2 and CO [4][16][17][18][19][20

• ., analgesia, anti-inflammation, antihypertension and many more (DB06889, DB07397, DB08777) [47][48][49][50][51][52][53][54][55][56]. Thienopyrimidone derivatives have also been used in the context of other Gewald-based MCRs in the past, but the reported diversity has been rather low [57][58][59][60]. The

• anthranilic acid and B) access to heteroannulated pyrimidones by MCRs of suitably substituted heterocycles and formamide as C1 source. Access to the key building blocks 2–4 by employing three different nonisocyanide-based MCRs. Diversity and complexity were the essential features of our library of starting

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

Synthesis, characterization, and photophysical properties of novel 9‑phenyl-9-phosphafluorene oxide derivatives

• Shuxian Qiu,
• Duan Dong,
• Jiahui Li,
• Huiting Wen,
• Jinpeng Li,
• Yu Yang,
• Shengxian Zhai and
• Xingyuan Gao

Beilstein J. Org. Chem. 2024, 20, 3299–3305, doi:10.3762/bjoc.20.274

• access to PhFlOP-based TADF emitters. Additionally, the design of TADF emitters with the PhFlOP acceptor moiety and the carbazole donor moiety is lacking structural diversity. Herein, we present a 5-step synthesis of several novel D−A−D-type PhFlOP derivatives with substituted carbazole groups as donors

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

• benziodoxolone was generated in situ, via a reaction of chlorobenziodoxolone with sulfinate salts, followed by the addition of amines or hydrazines, respectively. On the follow-up on our research, we envisaged to extend the diversity of BBX reagents as electrophilic amine reagents and investigated their