Synthesis of substituted triazole–pyrazole hybrids using triazenylpyrazole precursors

• Simone Gräßle,
• Laura Holzhauer,
• Nicolai Wippert,
• Olaf Fuhr,
• Martin Nieger,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2024, 20, 1396–1404, doi:10.3762/bjoc.20.121

• addition, the compatibility of the method with solid-phase synthesis is shown exemplarily. Keywords: azide; click reaction; CuAAC; pyrazole; triazene; triazole; Introduction Nitrogen-containing heterocycles are central scaffolds in medicinal chemistry and are incorporated in most small-molecule drugs [1

Sustainable tandem acylation/Diels–Alder reaction toward versatile tricyclic epoxyisoindole-7-carboxylic acids in renewable green solvents

• Ayhan Yıldırım

Beilstein J. Org. Chem. 2024, 20, 1308–1319, doi:10.3762/bjoc.20.114

• applications [15][16]. These oils are of increasing interest for the production of a wide range of polymeric materials [17][18][19][20][21][22][23], drug delivery systems [24][25][26][27][28][29], less toxic anticancer drugs [30][31][32][33] and intermediates suitable for various organic transformations [14

The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetamide carboxamide oxindole hybrids

• Carolina S. Marques,
• Aday González-Bakker and
• José M. Padrón

Beilstein J. Org. Chem. 2024, 20, 1213–1220, doi:10.3762/bjoc.20.104

• urgent need to find novel, effective and safe drugs for cancer therapy. Recently, focusing on the design of more potent anticancer drug candidates using more sustainable synthetic processes, we report a new Ugi four-component reaction approach for easy access to Ugi-derived isatin-peptoids in moderate to

Cofactor-independent C–C bond cleavage reactions catalyzed by the AlpJ family of oxygenases in atypical angucycline biosynthesis

• Jinmin Gao,
• Liyuan Li,
• Shijie Shen,
• Guomin Ai,
• Bin Wang,
• Fang Guo,
• Tongjian Yang,
• Hui Han,
• Zhengren Xu,
• Guohui Pan and
• Keqiang Fan

Beilstein J. Org. Chem. 2024, 20, 1198–1206, doi:10.3762/bjoc.20.102

• Sciences, No. 1 Yanqihu East Road, Beijing 101408, China State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191, China 10.3762/bjoc.20.102 Abstract Biosynthesis of atypical angucyclines involves unique oxidative B-ring

Stability trends in carbocation intermediates stemming from germacrene A and hedycaryol

• Naziha Tarannam,
• Prashant Kumar Gupta,
• Shani Zev and
• Dan Thomas Major

Beilstein J. Org. Chem. 2024, 20, 1189–1197, doi:10.3762/bjoc.20.101

• anticancer, antimalarial, antibacterial, and antiviral activity [8][9]. For instance, the well-known artemisinin family of drugs, which is currently the first line of treatment against malaria, is a sesquiterpene lactone [10]. Sesquiterpenes produced by plants [10] also have plant growth regulating and

Bismuth(III) triflate: an economical and environmentally friendly catalyst for the Nazarov reaction

• Manoel T. Rodrigues Jr.,
• Aline S. B. de Oliveira,
• Ralph C. Gomes,
• Amanda Soares Hirata,
• Lucas A. Zeoly,
• Hugo Santos,
• João Arantes,
• Catarina Sofia Mateus Reis-Silva,
• João Agostinho Machado-Neto,
• Leticia Veras Costa-Lotufo and
• Fernando Coelho

Beilstein J. Org. Chem. 2024, 20, 1167–1178, doi:10.3762/bjoc.20.99

• found in a series of natural products and synthetic molecules with different biological activities [11][80][81]. In particular, 1-indanones substituted in position 3 are important synthons for some drugs and natural products [82][83][84]. A bibliographic survey revealed that some methods were developed

Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• ][3][4][5]. Full inhibition of CDA leads to accumulation of toxic pyrimidine catabolism intermediates [6][7]. However, local and temporary inhibition of CDA in the liver provides a therapeutic benefit by allowing cytosine analogue-containing drugs to bypass the liver with an intact nucleobase

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

• the replication by acting as a delayed chain terminator or by causing genetic corruption in the viral RNA and includes the first FDA-approved antiviral drugs in the therapy of COVID-19 patients, remdesivir [10] and molnupiravir [11]. The usability of NAIs may largely depend on the metabolic activation

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

Innovative synthesis of drug-like molecules using tetrazole as core building blocks

• Jingyao Li,
• Ajay L. Chandgude,
• Qiang Zheng and
• Alexander Dömling

Beilstein J. Org. Chem. 2024, 20, 950–958, doi:10.3762/bjoc.20.85

• complexity of chemical synthesis towards novel drugs has almost doubled from eight chemical steps to an average of 14 in 2021 [1]. Therefore, the need for robust reactions compatible with many functional groups in complex molecules is an integral part in contemporary medicinal chemistry and drug development

• , metabolic stability, conformational rigidity, and potency [7][8][9]. Recently, the use of the tetrazole moiety in drug development has been increased and exhibited prevalent occurrence in bioactive compounds; being present in more than 20 marketed drugs with a very broad range of biological activities such

• . Tetrazole drugs, current assembly strategies, and novel building block strategy. Synthesis of tetrazole building blocks. Isolated yields. Substrate scope of Passerini products 3. Isolated yields. Substrate scope of Ugi products 4 and 5. Isolated yields. Synthesis of tetrazole building block 6. Isolated

Enantioselective synthesis of β-aryl-γ-lactam derivatives via Heck–Matsuda desymmetrization of N-protected 2,5-dihydro-1H-pyrroles

• Arnaldo G. de Oliveira Jr.,
• Martí F. Wang,
• Rafaela C. Carmona,
• Danilo M. Lustosa,
• Sergei A. Gorbatov and
• Carlos R. D. Correia

Beilstein J. Org. Chem. 2024, 20, 940–949, doi:10.3762/bjoc.20.84

• -lactam ring is a privileged scaffold widely present in drugs and natural products [12][13][14], as shown in Scheme 1. Herein, we report the effective desymmetrization strategy of N-protected 2,5-dihydro-1H-pyrroles using aryldiazonium salts and the chiral N,N-ligand (S)-PyraBox (Scheme 2). The obtained

• the (S)-PyraBox–palladium complex. Examples of drugs containing a γ-lactam and derivative. Desymmetrization strategies employing Heck-Matsuda reactions. Heck–Matsuda reaction (1) and Jones oxidation (2) of the N-Boc-protected 2,5-dihydro-1H-pyrrole 1a. Reaction conditions: 1) pyrroline 1a (0.30 mmol

One-pot Ugi-azide and Heck reactions for the synthesis of heterocyclic systems containing tetrazole and 1,2,3,4-tetrahydroisoquinoline

• Jiawei Niu,
• Yuhui Wang,
• Shenghu Yan,
• Yue Zhang,
• Xiaoming Ma,
• Qiang Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2024, 20, 912–920, doi:10.3762/bjoc.20.81

• ; Introduction Tetrazole is a privileged heterocycle existing in a range of biological and medicinally interesting compounds [1][2] with antifungal [3][4], antibacterial [5], anticancer [6][7], antiparasitic [8], and antihypertensive properties [9] including FDA approved drugs such as valsartan and cefmetazole

Synthesis and properties of 6-alkynyl-5-aryluracils

• Ruben Manuel Figueira de Abreu,
• Till Brockmann,
• Alexander Villinger,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 898–911, doi:10.3762/bjoc.20.80

• anticarcinogenic studies followed in 1953 [7][8]. Since then, uracil has played an important role in the development of antiviral and anticarcinogenic agents against various targets [9][10][11][12][13][14][15][16]. 5-Fluorouracil is one of the best-known anticancer drugs and is used to treat a variety of cancers

• proven medical potential of uracil, further investigation was carried out to fully utilize the synthetic possibilities uracil has to offer and to synthesize new drugs against existing or hitherto unknown targets. Moreover, studies have even shown that a sugar moiety is not always required to act against

• layers were dried over Na2SO4, concentrated under reduced pressure, and purified by column chromatography (heptane/ethyl acetate). Uracil derivatives in drugs. Present work as compared to previous studies [25][57][58][59]. ORTEP diagram of 5a front view (a) and side view (b). a) Interactions of the

Three-component N-alkenylation of azoles with alkynes and iodine(III) electrophile: synthesis of multisubstituted N-vinylazoles

• Jun Kikuchi,
• Roi Nakajima and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2024, 20, 891–897, doi:10.3762/bjoc.20.79

• natural products and pharmaceutical agents, including antifungal drugs [1][2][3], and hence their selective preparation has attracted considerable attention from the synthetic community. Compared to methods for the de novo construction of azole heterocycles, direct functionalization of the azole N–H bond

Confirmation of the stereochemistry of spiroviolene

• Yao Kong,
• Yuanning Liu,
• Kaibiao Wang,
• Tao Wang,
• Chen Wang,
• Ben Ai,
• Hongli Jia,
• Guohui Pan,
• Min Yin and
• Zhengren Xu

Beilstein J. Org. Chem. 2024, 20, 852–858, doi:10.3762/bjoc.20.77

• Yao Kong Yuanning Liu Kaibiao Wang Tao Wang Chen Wang Ben Ai Hongli Jia Guohui Pan Min Yin Zhengren Xu State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China; Ningbo Institute of Marine Medicine, Peking University, Ningbo

Synthesis of new representatives of A₃B-type carboranylporphyrins based on meso-tetra(pentafluorophenyl)porphyrin transformations

• Victoria M. Alpatova,
• Evgeny G. Rys,
• Elena G. Kononova and
• Valentina A. Ol'shevskaya

Beilstein J. Org. Chem. 2024, 20, 767–776, doi:10.3762/bjoc.20.70

• known to enhance the aqueous solubility and tumor selectivity of hydrophobic drugs through the enhanced permeability and retention effect [46]. It was also shown that porphyrin 6 undergoes reaction with taurine (2-aminoethanesulfonic acid, 25) which is an essential nutraceutical with diverse

Methodology for awakening the potential secondary metabolic capacity in actinomycetes

• Shun Saito and
• Midori A. Arai

Beilstein J. Org. Chem. 2024, 20, 753–766, doi:10.3762/bjoc.20.69

• therapeutic drugs [1], agrochemicals [2], veterinary medicines [3], medium supplements for selective microbial/cell culture [4][5][6], food preservatives/colorings [7][8], and biochemical reagents for pharmacological/chemical biology studies [9]. This review has focused particularly on compounds produced by

Research progress on the pharmacological activity, biosynthetic pathways, and biosynthesis of crocins

• Zhongwei Hua,
• Nan Liu and
• Xiaohui Yan

Beilstein J. Org. Chem. 2024, 20, 741–752, doi:10.3762/bjoc.20.68

• glutathione peroxidase (GPx) [34]. The current clinical treatment of epilepsy relies on the use of antiepileptic drugs. However, the occurrence of drug-resistant epilepsy is a top-priority problem [35][36][37]. It was found that intravenous injection of 50 μg crocin could delay epileptiform activity in mice

• broad pharmacological properties. They are promising drugs for treating cardiovascular and liver diseases. Despite numerous pharmacological properties, the exact mechanisms of action of crocins remain elusive. The therapeutic potential of crocins is impeded by the limited bioavailability and rapid

Regioselective quinazoline C2 modifications through the azide–tetrazole tautomeric equilibrium

• Dāgs Dāvis Līpiņš,
• Andris Jeminejs,
• Una Ušacka,
• Anatoly Mishnev,
• Māris Turks and
• Irina Novosjolova

Beilstein J. Org. Chem. 2024, 20, 675–683, doi:10.3762/bjoc.20.61

• efficiencies [5][6][7]. Consequently, ongoing efforts focus on advancing methodologies for synthesizing established quinazoline-based drugs and acquiring novel modified quinazoline derivatives for pharmaceutical or materials science purposes. Aromatic nucleophilic substitution [8] or metal-catalyzed reactions

• quinazolines [17][18], and sulfonyl group rearrangement has been applied to functionalize purines [19], the literature lacks information on sulfonyl group migration in quinazolines. Notably, this transformation has not been previously reported, despite its potential utility in the synthesis of drugs such as

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• owing to their wide applications in medicinal chemistry [1][2][3][4][5]. γ- and ε-AA derivatives are widely distributed in peptide natural products, bioactive molecules, and drugs, such as pregabalin, baclofen, ε-aminocaproic acid and lysine (Scheme 1a) [6][7][8][9][10][11][12]. The number of reported

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

• Luan A. Martinho and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2024, 20, 628–637, doi:10.3762/bjoc.20.55

• Luan A. Martinho Carlos Kleber Z. Andrade Instituto de Química, Laboratório de Química Metodológica e Orgânica Sintética (LaQMOS), Universidade de Brasília, 70904-970, Brasília, DF, Brazil 10.3762/bjoc.20.55 Abstract The imidazo[1,2-a]pyridine moiety is present in drugs with several biological

• existing ones. Keywords: GBB-3CR; imidazo[1,2-a]pyridine; microwave; phosphotungstic acid; Introduction Imidazo[1,2-a]pyridine is a privileged structure that plays an important role in organic synthesis and in the pharmaceutical industry. This scaffold is present in drugs with several biological

• activities, such as antiviral [1], anticonvulsant [2], antibacterial [3], antipyretic [4], antituberculosis [5], anticancer [6], anthelmintic [5], antifungal [7], analgesic [8], antiulcer [9], antiprotozoal [10], antitumor [11], and anti-inflammatory [12]. Examples of commercial drugs are depicted in Figure

Chemical and biosynthetic potential of Penicillium shentong XL-F41

• Ran Zou,
• Xin Li,
• Xiaochen Chen,
• Yue-Wei Guo and
• Baofu Xu

Beilstein J. Org. Chem. 2024, 20, 597–606, doi:10.3762/bjoc.20.52

• , and anticancer properties [6][7]. Historically, most alkaloids were isolated from higher plants, with a significant number found in the Apocynaceae family. Notable examples such as vinblastine, vinorelbine, vincristine, and vindesine have gained prominence as effective anticancer drugs [6][7][8][9][10

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

• ) or a bromine atom. These transformations yield spiro-annulated O-heterocycles with succinimide ring, namely spiro-Δα,β-butenolides 2 and 3, tetrahydrofurans 4 and benzopyrans 5 (Scheme 1). Fragments of these oxygen-containing spiro-conjugated heterocycles are part of many important drugs and natural

• including aldosterone receptor antagonistic [22], anti-inflammatory [23], and anti-HIV [24] activity. Substantial drugs based on spirocyclic tetrahydrofuran and pyran moieties include spironolactone (a multi-target drug that is primarily used to treat high blood pressure and heart failure) [25

• multitarget drugs against COVID-19 [36], and amiaspochalasin C isolated from the solid culture of Aspergillus micronesiensis [37] and 1,9-epoxy-9a-hydroxystenine from the roots of Stemona tuberosa [38]) (Figure 1). Hence, the development of novel synthetic methods to construct spiro O-heterocycles constitutes

A new analog of dihydroxybenzoic acid from Saccharopolyspora sp. KR21-0001

• Rattiya Janthanom,
• Yuta Kikuchi,
• Hiroki Kanto,
• Tomoyasu Hirose,
• Arisu Tahara,
• Takahiro Ishii,
• Arinthip Thamchaipenet and
• Yuki Inahashi

Beilstein J. Org. Chem. 2024, 20, 497–503, doi:10.3762/bjoc.20.44

• metabolites from the rare actinomycete Saccharopolyspora sp. KR21-0001. As a result, KR21-0001A (1), a new analog of dihydroxybenzoic acid, was discovered as a potent antioxidant. In conclusion, exploring rare actinomycetes for bioactive compound discovery represents a promising way in the quest for new drugs

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• present in many agrochemical and pharmaceutical products owing to the beneficial properties imparted such as increased metabolic stability, lipophilicity and bioavailability of the bioactive entity [1][2][3]. In 2018, 30% of FDA approved drugs contained at least one fluorine atom, with an average of 2.7