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

• this context, quinoline and its derivatives are privileged structures in several natural products and biologically active compounds, rendering this scaffold an important synthetic target. An attractive strategy to afford tetrahydroquinolines and quinolines is the Povarov reaction, a type of aza-Diels

• in MCR reactions applied to the synthesis of propargylamines and aminophosphonates. We will discuss the reaction conditions, mechanisms, and scope. Synthesis of propargylamines Propargylamines are essential building blocks for the synthesis of natural products or biologically active compounds in

Vinylogous functionalization of 4-alkylidene-5-aminopyrazoles with methyl trifluoropyruvates

• Judit Hostalet-Romero,
• Laura Carceller-Ferrer,
• Gonzalo Blay,
• Amparo Sanz-Marco,
• José R. Pedro and
• Carlos Vila

Beilstein J. Org. Chem. 2025, 21, 533–540, doi:10.3762/bjoc.21.41

• biologically active compounds, particularly antibacterial and antifungal agents [13][14]. This class of functionalized nitrogen heterocycles is notable for its synthetic versatility, because it shows different nucleophilic positions, making regioselectivity a synthetic challenge. Numerous studies have reported

• functionalize 5-aminopyrazoles. Biologically active compounds featuring a trifluoromethyl carbinol motif. Nucleophilic sites of 5-aminopyrazoles and 4-alkenyl-5-aminopyrazoles. Stereoselective synthesis of trifluoromethyl carbinols through an vinylogous addition reaction of 4-alkenyl-5-aminopyrazoles to alkyl

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

• secondary amines via an N-acyl nitrene intermediate [77]. Amidines, found in biologically active compounds, have been widely investigated in medicinal chemistry due to their potent antiviral, antibacterial, anticancer, and other therapeutic properties [78][79][80][81]. As shown in Scheme 4, dioxazolones

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

• , also in regio- and stereoselective processes. The interest for these strategies arises from the cost-effectiveness as one-pot processes, the ease of application and the great efficiency when directed to the synthesis of biologically active compounds. Plausible general catalytic activation for ionic or

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• imines; asymmetric organocatalysis; cyclization; N-heterocycles; inverse electron demand aza-Diels–Alder reaction; Introduction Nitrogen-containing heterocycles are abundant scaffolds present in natural products, biologically active compounds, pharmaceuticals, synthetic agrochemicals, and functional

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• mesh) as a stationary phase (eluent n-hex/AcOEt 5:95%). Representative examples of fluorine containing, biologically active compounds. Possible mechanisms for the reaction of 1a and 2a leading to 3a (via B), proceeding via either halogen-bonded adducts and reductive elimination (path 1) or directly via

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

• Although less common than fluorine in biologically active compounds, chlorine-containing molecules have interest in drug discovery, with over 250 chloro-containing drugs presently available [43]. The introduction of a chlorine atom into biologically active compounds for use in pharmaceuticals and

gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides

• Monika Bilska-Markowska,
• Marcin Kaźmierczak,
• Wojciech Jankowski and
• Marcin Hoffmann

Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247

• acceptors [13][14][15][16][17]. The Michael addition with fluorinated acceptors finds application in the synthesis of, among others, fluorinated amino acids, which can be a structural motif in many biologically active compounds [18]. There are also known studies on the incorporation of highly reactive

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• biologically active compounds and natural products. Consequently, the synthesis of aryl sulfides has drawn increasing attention. Diaryliodonium salts have been reported to be utilized to arylate thiols in a number of publications in recent years [44][86][87]. In 2022, Sarkar et al. demonstrated a synthesis of

Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

• Kento Iwai,
• Akari Hikasa,
• Kotaro Yoshioka,
• Shinki Tani,
• Kazuto Umezu and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2024, 20, 2827–2833, doi:10.3762/bjoc.20.238

• acidic propargyl methylene group. Among these, polycarbonylated propargylamines (PCPAs), specifically N,1-dicarbonylated or N,1,1-tricarbonylated propargylamines, are often used as model compounds to identify biologically active compounds [7][8][9][10] or their synthetic precursors [11][12][13][14][15

• biologically active compounds [27][28][29][30][31] and their synthetic intermediates [32][33][34][35][36]. Thus, this method, which enables modification at the 2- and 5-positions of oxazole-4-carboxylates, is a valuable tool for the study of these compounds. Experimental General All reagents except for DEMO

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

• filtered off, washed with water (2 × 5 mL) and recrystallized from a mixture of DMF/iPrOH 1:2. The title compounds 5a–e were obtained as white solids. Some biologically active compounds and organic fluorophores containing the imidazo[1,2-a]pyrimidine nucleus. Existing approaches to imidazo[1,2-a

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

• preparation of biologically active compounds [15]. The synthesis was achieved via a sulfonyl group rearrangement driven by the azide–tetrazole equilibrium in quinazolines. The researchers utilized two synthetic pathways to prepare the target compounds. The first pathway involved a nucleophilic aromatic

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

• -1,1-dioxide motif is presented in a number of biologically active compounds including important market drugs as antiglaucoma agent dorzolamide [21], diuretic/anticancer meticrane [22] and antiherpesvirus agent amenamevir (ASP-2151) [23] which was recently synthesized by Ugi-4CR [24] (Scheme 1C

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• ); isoquinolinone; solvent-dependence; Introduction Isoquinolinone is an important heterocyclic structure found in many natural products and biologically active compounds, including pharmaceuticals [1]. For instance, lycoricidine, found in the medicinal plant Lycoris radiata, may inhibit the MCPyV LT protein

• . Selected natural products, pharmaceuticals, and biologically active compounds having an isoquinolinone scaffold. Chemoselective and PISA-mediated, solvent-controlled synthesis of different isoquinolinone derivatives 2 and 3. Substrate scope for the synthesis of 4-substituted isoquinolinones 2. Reaction

A facile three-component route to powerful 5-aryldeazaalloxazine photocatalysts

• Ivana Weisheitelová,
• Radek Cibulka,
• Marek Sikorski and
• Tetiana Pavlovska

Beilstein J. Org. Chem. 2024, 20, 1831–1838, doi:10.3762/bjoc.20.161

• potent, biologically active compounds. Interestingly, the introduction of a strong methoxy group at position 7 of the 5-aryldeazaalloxazine core led to a bathochromic shift in the absorption spectra of the synthesised molecules, making them more suitable for visible light photocatalysis. Experimental

Generation of multimillion chemical space based on the parallel Groebke–Blackburn–Bienaymé reaction

• Evgen V. Govor,
• Vasyl Naumchyk,
• Ihor Nestorak,
• Dmytro S. Radchenko,
• Dmytro Dudenko,
• Yurii S. Moroz,
• Olexiy D. Kachkovsky and
• Oleksandr O. Grygorenko

Beilstein J. Org. Chem. 2024, 20, 1604–1613, doi:10.3762/bjoc.20.143

• showed biological activity according to the ChEMBL database. Keywords: fused rings; heterocycles; imidazoles; isonitrile; multicomponent reactions; Introduction Multicomponent reactions are widely recognized as a powerful source of biologically active compounds, in particular, for drug discovery

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• synthesis; electrophotocatalysis; radical decarboxylation; Introduction Alkylnitriles and their derivatives are widely found in pharmaceuticals and biologically active compounds [1][2][3]. In addition, within the field of synthetic organic chemistry, nitriles are synthetically useful handles that can be

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• where other methods of oxidation or reduction might be challenging or impractical. The present discussion focuses on some recent synthetic advances and their application in biologically active compounds. Lewis acid-catalyzed intramolecular Cannizzaro reaction Wang et al. [73] depicted a highly

Novel analogues of a nonnucleoside SARS-CoV-2 RdRp inhibitor as potential antivirotics

• Luca Julianna Tóth,
• Kateřina Krejčová,
• Milan Dejmek,
• Eva Žilecká,
• Blanka Klepetářová,
• Lenka Poštová Slavětínská,
• Evžen Bouřa and
• Radim Nencka

Beilstein J. Org. Chem. 2024, 20, 1029–1036, doi:10.3762/bjoc.20.91

• still scarce. Recently, many studies have been focusing on drug repurposing or screening libraries of already approved biologically active compounds [16][17]. This approach might represent a very promising strategy in the case of targeting the coronaviral RdRp due to the highly conserved structure of

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

• ][4]. The indole core is particularly noteworthy for its role in various biologically active compounds and drugs, such as antihypertensives, anti-inflammatories, antimycotics, antimigrants, anticancer drugs, and many others [5][6][7]. The first synthesis of indole has been introduced by Fischer in

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• properties are exhibited by compounds based on a THF and THP core spiro-conjugated with the pyrrolidine ring. These frameworks are present in a number of synthetic biologically active compounds (such as NaV1.7 blocker XEN907 for the treatment of pain [31], σ1 receptor ligand 6 [32], histamine-3 receptor

• )ethanol. In the latter case, the predominant process was found to be the base-promoted migration of the C=C bond of the arylidene fragment into the cycle. Examples of biologically active compounds and natural products based on THF/THP spiro-conjugates with pyrrolidine rings. DAS spirocyclizations reported

Cycloaddition reactions of heterocyclic azides with 2-cyanoacetamidines as a new route to C,N-diheteroarylcarbamidines

• Pavel S. Silaichev,
• Tetyana V. Beryozkina,
• Vsevolod V. Melekhin,
• Valeriy O. Filimonov,
• Andrey N. Maslivets,
• Vladimir G. Ilkin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2024, 20, 17–24, doi:10.3762/bjoc.20.3

• of hybrids of 1,2,3-triazole with other heterocycles and to identify biologically active compounds among the synthesized compounds. It is known that the cycloaddition reaction of azidopyrimidinediones with enamines [13] represents an effective method for the synthesis of pyrimidinyl amidines [14

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• scaffold can be found in many biologically active compounds and natural products such as 1-epiaustraline, hyacinthacine A1, (−)-isoretronecanol, and (−)-supinidine (Figure 2) [68][69]. After the method development work, a pseudo-five-component double cycloaddition reaction of glycine with two equivalents

• pyrrolizidines shown in Scheme 6 and Scheme 7, we then conducted similar reactions in order to synthesize spirooxindole-pyrrolidines. This unique ring skeleton exists in some natural products and biologically active compounds such as (−)-horsfiline, (+)-alstonisine, pteropodine and spirotryprostatin A (Figure 3

Secondary metabolites of Diaporthe cameroonensis, isolated from the Cameroonian medicinal plant Trema guineensis

• Bel Youssouf G. Mountessou,
• Élodie Gisèle M. Anoumedem,
• Blondelle M. Kemkuignou,
• Yasmina Marin-Felix,
• Frank Surup,
• Marc Stadler and
• Simeon F. Kouam

Beilstein J. Org. Chem. 2023, 19, 1555–1561, doi:10.3762/bjoc.19.112

• far from being accessed [2][3], they have been considered as an untapped microbial reservoir capable of producing a wide range of structurally unique natural products with potent pharmacological effects [4]. However, the production of biologically active compounds by filamentous fungi, especially

New one-pot synthesis of 4-arylpyrazolo[3,4-b]pyridin-6-ones based on 5-aminopyrazoles and azlactones

• Vladislav Yu. Shuvalov,
• Ekaterina Yu. Vlasova,
• Tatyana Yu. Zheleznova and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2023, 19, 1155–1160, doi:10.3762/bjoc.19.83

• when irradiated with UV light. Keywords: 5-aminopyrazole; azlactone; elimination; fluorescence; one-pot synthesis; pyrazolo[3,4-b]pyridin-6-one; Introduction The pyrazolo[3,4-b]pyridine scaffold is present in many biologically active compounds [1][2][3][4][5][6][7][8][9][10][11][12]. Among them, 4