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

• , commonly referred to as sulfa drugs. These include top seller drugs, e.g., antimicrobials, anti-inflammatories, antihypertensives, and antitumor agents [24][25][26]. Particularly, the sulfonamide motif can act as a bioisostere of carboxylic acids, establishing a set of hydrogen bonds similar to those

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

• or fluoroalkyl motifs into organic molecules or key frameworks stands out as a crucial and appealing approach in uncovering and crafting innovative drugs, agrochemicals, and functional materials (Figure 1) [1][2][3][4]. Fluorinated functional groups can positively alter the electronic characteristics

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

• acetylcholinesterase (AChE) on ACh. Among the five drugs prescribed for AD, four (donepezil, rivastigmine, galantamine, and tacrine) are built upon the cholinergic hypothesis [26]. In contrast, memantine emerges as the only drug available that targets the glutamatergic system for AD, functioning as a non-competitive

• concentrations in the later stages of this pathology, has been gaining attention for the treatment of this disease. In 2021, Brandão et al. [33] developed a series of molecules inspired by the oxoindole-β-lactam core, a structural motif, present in many acetylcholinesterase inhibitor drugs, through the Ugi

• (IC50 = 1.28 μM), and non-toxicity in liver HepG2 cells. Hantzsch-based strategies: As mentioned before, in response to the challenges posed by the multifactorial nature of AD, the MTDL approach has emerged as a promising strategy. This approach involves designing drugs capable of binding simultaneously

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

• cost effective and selective, one-pot transformation. Pharmaceutical uses for bio-active cyclic molecules accessible by I(III) reagents are plentiful; anticancer drugs can be formed from the basis of pyrrolo[2,3-b]indoles 1 [3][4], 2-oxazolines 2 [5][6], dihydrofuran 3 [7][8], and spirocyclic scaffolds

• activity of biologically relevant molecules [22], and compounds containing fluorine have seen huge success in medicine and agrochemicals, with over 30% of small molecule drugs [23][24] and 16% of pesticides [25] now containing fluorine atoms. A range of synthetically important fluorinated hetero- and

• 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

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• applied in various fields, including organometallic catalysis, dye-sensitized solar cells, sensing, artificial olfactory systems, photodynamic therapy (PDT), anticancer drugs, biochemical probes, and electrochemical devices. Relevant examples of these two pyrrolic macrocycles as metal-free organocatalysts

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

• are found in a plethora of compounds with significant biological and pharmacological relevance [1][2][3][4]. These moieties are indispensable in the design and synthesis of novel drugs aimed at overcoming drug resistance, which is a global health threat [5][6][7]. To date, a strategy to access novel

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

• traditional medicine formulations [2]. Modern science has found that natural products are uniquely suited as the starting point for the development of new drugs [3][4]. They may serve as chemical probes and help confirm laboratory findings [5]; furthermore, entirely new physical and chemical principles are

Synthesis of pyrrole-fused dibenzoxazepine/dibenzothiazepine/triazolobenzodiazepine derivatives via isocyanide-based multicomponent reactions

• Marzieh Norouzi,
• Mohammad Taghi Nazeri,
• Ahmad Shaabani and
• Behrouz Notash

Beilstein J. Org. Chem. 2024, 20, 2870–2882, doi:10.3762/bjoc.20.241

• compounds with antibiotic, antiviral, and anticancer properties that are found in many drugs and natural products [1][2][3][4][5][6]. Pyrroles' biological properties manifest when they are fused to other heterocycles [7][8][9][10][11][12]. Among them, seven-membered heterocycles of the benzodiazepine

• , benzoxazepine, and benzothiazepine derivatives are especially important. These consitute the central core of many natural and biological compounds and commercial drugs, including diazepam, clonazepam, lorazepam, telenzepine, chlordiazepoxide, loxapine, and amoxapine [13][14][15][16][17][18][19][20][21]. Pyrrole

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• controlled by such protein kinases. Therefore, the investigation of the influence of drugs on protein kinases plays an important role in current medicinal chemistry. Indigo naturalis is a traditional drug, derived from indigo plants, which has been used in China for centuries and also more recently against

• anticipated that PAM activates channels of the membrane of melanoma cells to allow the antiproliferative compound (β-33b) to enter the cell. Thus, β-33b combined with PAM might be developed to a new and promising method of therapeutic intervention. This concept of combination of PAM with drugs could also be

• -glycososides 3-Alkylideneoxindoles are of considerable pharmacological relevance and occur in a variety of clinically used drugs and natural products [42][43][44][45]. The reaction of isatin-N-rhamnoside 16a with acetophenone (45a) afforded the desired 3-alkylideneoxindole-N-rhamnoside E-β-46a in good yield as

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

• structural element of divaplon [7], fasiplon and taniplon [8], which are anxiolytics and anticonvulsant drugs. However, their application in clinical practice was recently discontinued [9][10]. The use of imidazo[1,2-a]pyrimidine derivatives as effective antifungal agents is worthy of particular attention

• polysubstituted hydrogenated heterocyclic structures on their basis [25][26][27][28], including an acetanilide fragment. The introduction of this fragment into a molecule, often drugs, enhances the cytotoxic, antibacterial, and antiviral activity of the compounds, thus widening the range of their potential

• applications [28][29] including as antifungal agents [30][31][32][33]. These findings are supported by a number of literature sources that highlight the importance of incorporating the acetanilide moiety into potential drugs, including for enhancing the pharmacological activity of imidazo[1,2-a]pyrimidines [1

Synthesis of benzo[f]quinazoline-1,3(2H,4H)-diones

• Ruben Manuel Figueira de Abreu,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2708–2719, doi:10.3762/bjoc.20.228

• promising target and candidate for the development of new drugs against a wide range of diseases [1][2][3][4]. As it is not contained in the DNA, it could be used to distinguish between DNA and RNA-based pharmaceutical targets. In previous years, uracil has been successfully used in the development of

• several drugs that are still important and often used. Examples include 5-fluorouracil and brivudine. 5-Fluoruracil is an important anticancer drug, while brivudine is considered to be one of the most effective antiviral drugs against the HSV-1 virus [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18

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

• performance. In their contribution “Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs”, Moutayakine and Burke described a new synthetic route for the synthesis of 10,11-dihydro-5H-dibenzo[b,e][1,4]diazepinone (DBDAP

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• anticancer effects [1]. Amongst these, 2-hydroxybenzophenones are regarded as one of the most important classes of compounds owing to their varied bioactivities, including calcium channel blockers, anti-influenza drugs, anti-HAV drugs, and antispasmodic agents (Figure 1) [2]. Along with that, oxybenzone, a 2

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

• , including drugs and alkaloids [8]. Several drugs are known to contain the 2-pyridone structure, such as the cardiotonic drugs milrinone (Figure 1c) and amrinone (Figure 1d) [9][10], as well as the antibiotic pilicide (Figure 1e) [11][12]. As described in [13] during preliminary experiments, it was

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

• , 52074, Aachen, Germany 10.3762/bjoc.20.214 Abstract With the resurgence of electrosynthesis in organic chemistry, there is a significant increase in the number of routes available for late-stage functionalization (LSF) of drugs. Electrosynthetic methods, which obviate the need for hazardous chemical

• , these protocols are poised to become a vital component of the medicinal chemist's toolkit. In this review, we discuss electrochemical protocols that have been demonstrated to be applicable for the LSF of pharmaceutical drugs, their derivatives, and natural substrates. We present and analyze

• representative examples to illustrate the potential of electrochemistry or photoelectrochemistry for the LSF of valuable molecular scaffolds. Keywords: electrochemistry; late-stage functionalization; paired electrolysis; pharmaceutical drugs; photoelectrochemistry; Introduction Organic electrochemistry is

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

• ], electronic effects [17][18], and conformation [19][20][21]. Some trifluoromethoxylated molecules can be used as drugs in the treatment of various pathologies (Figure 1) [22][23][24][25][26][27][28][29]. On the other hand, despite its toxicity at higher doses, selenium is also an essential trace element in

• by chromatography. Examples of trifluoromethoxylated drugs. Proposed mechanism of the reaction and 19F NMR of the DDPYOCF3/PhSeBr mixture. Phenylseleno trifluoromethoxylation of various alkenes. Yields determined by 19F NMR spectroscopy with PhCF3 as internal standard (in parentheses isolated yields

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• heterocycles are classified as privileged medicinal scaffolds being components of many drugs [13][14]. Thiazole derivatives and their reduced forms exhibit antitumor (thiazofurin, ixabepilone), antibacterial (cefotaxime, ceftaroline, cefiderocol), antifungal (isavuconazole, fosravuconazole), antiviral

• (simeprevir, ritonavir, cobicistat), and other types of biological activities [15][16][17][18][19]. Besides, among the registered sulfur-containing drugs, 19% contain a thiazole ring, and 15% contain a thioether group [20]. Oxadiazole fragments are found in the structures of anticancer drugs (zibotentan

• ), antituberculosis agents [13], as well as in drugs against arrhythmia (nesapidil) or muscular dystrophy (ataluren) [21]. The 1,3,4- and 1,2,4-oxadiazoles are the most promising from the point of view of bioactivity among the four isomers of oxadiazole. The presence of a 1,3,4-oxadiazole ring in the structure of

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

• the possible substitution patterns, meta-substituted anilines hold a special place. These compounds are difficult to access due to the inherent ortho-/para-directional reactivity of the amino group, at the same time they are widely used in medicinal chemistry, resulting in several marketed drugs

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

• -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

• reaction (A) and examples of DHMP (B) and thiopyran-1,1-dioxide (C) containing drugs. Scope of the obtained Biginelli products 2a–q. Synthesis of SO2-containing enastron analogue 2r. Postmodification of the Biginelli product 2a. Optimization of reaction. Supporting Information Supporting Information File

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

• docking software (unfortunately not free) designed to predict the conformations of small molecules in protein binding sites, thus facilitating the discovery of new drugs. Within SeeSAR, its functionality allows ligands to be placed in binding sites using an incremental construction algorithm that splits

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

• ][5][6]. For instance, pyrazoles serve as monoamine oxidase A and B inhibitors [7] and as COX-II inhibitors [8], making them valuable analgesics [9]. Furthermore, several blockbuster drugs, such as VIAGRA® [10], Celecoxib® [11], and Rimonabant [12], contain pyrazole cores. In addition, extensive

Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates

• Deepa Nair,
• Abhishek Tiwari,
• Banamali Laha and
• Irishi N. N. Namboothiri

Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177

• considerable interest in the stereoselective synthesis of the cyclohexanone skeleton as it constitutes the core structure in many natural products and pharmaceutical drugs [1][2]. Garsubellin A with a cyclohexanone skeleton is a potent inducer of choline acetyltransferase (ChAT) and could be used for the

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

• FDA-approved drugs in the United States contain at least one azacycle [33]. Therefore, the development of gentle and efficient methods for accessing these heterocycles is an ongoing pursuit for synthetic chemists. As mentioned above, with their two nitrogen atoms, hydrazones constitute unique synthons

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• of recently approved drugs by the FDA [31]. Fezolinetant (an NK3 receptor antagonist) and quizartinib (FLT3 inhibitor) are just a couple of examples among the drugs reaching the market in the last year. As shown in Scheme 2, ethyl (bromozinc)acetate (1a) was synthesized in flow by pumping a solution

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

• 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