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

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• cruciferous vegetables, as hydrolysis products from the metabolism of glucosinolates [1]. In 2017, Müller and her research team showcased the ability of BIMs to operate as anti-inflammatory drugs by acting as GPR84 agonists [2]. GPR84 is a protein-coupled receptor found in immune cells, which regulates a

• drugs by halting the growth of brain tumor cells and inhibiting the expression of inflammatory genes [7]. Since they can be administered orally, and they display satisfying distribution to the brain and plasma without leading to serious unwanted side effects, they have entered advanced stages of

• clinical trials as neuroprotective agents, presenting an attractive alternative to traditional anti-inflammatory and anti-Parkinson’s disease drugs [7]. With the increased drug resistance of bacteria to modern medicine, BIMs have emerged as an interesting alternative, due to their antibacterial and

Facile approach to N,O,S-heteropentacycles via condensation of sterically crowded 3H-phenoxazin-3-one with ortho-substituted anilines

• Eugeny Ivakhnenko,
• Vasily Malay,
• Pavel Knyazev,
• Nikita Merezhko,
• Nadezhda Makarova,
• Oleg Demidov,
• Gennady Borodkin,
• Andrey Starikov and
• Vladimir Minkin

Beilstein J. Org. Chem. 2024, 20, 336–345, doi:10.3762/bjoc.20.34

• and its derivatives are widely distributed in nature in microorganisms and fungi, and they represent the key structural units of many important drugs with antibacterial, antifungal, anticancer, anti-inflammatory, and antiviral activities [1][2]. Due to the presence of several reactive centers in the

Synthesis of spiropyridazine-benzosultams by the [4 + 2] annulation reaction of 3-substituted benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes

• Wenqing Hao,
• Long Wang,
• Jinlei Zhang,
• Dawei Teng and
• Guorui Cao

Beilstein J. Org. Chem. 2024, 20, 280–286, doi:10.3762/bjoc.20.29

• field [4][5][6]. Pyridazine drugs have also shown high pharmaceutical activity. Many types of pyridazine drugs have been listed for antibacterial, anti-inflammatory, and other purposes [7][8][9][10]. Nowadays, a range of transformations to spirobenzosultams have been established using N-sulfonyl

Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters

• Youlong Du,
• Haibo Mei,
• Ata Makarem,
• Ramin Javahershenas,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2024, 20, 212–219, doi:10.3762/bjoc.20.21

• esters; Introduction The insertion of fluorine-containing components frequently confers desirable physical and biological properties to organic molecules, and the development of fluorine-containing drugs is an important field of research [1][2][3][4][5][6][7][8][9]. It is estimated that 30% of drugs and

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• Yumei Wang Guangzhu Wang Yanping Zhu Kaiwu Dong School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Shandong

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• than the one-pot method. The most important of which was the chloro-containing DBDAP 4e that can be used to synthesize the antipsychotic drug clozapine (see above), a triazole-hybrid with anticancer properties, and can easily be used as the key part in the synthesis of other drugs like dibenzepine and

Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions

• Julika Schlosser,
• Olga Fedorova,
• Yuri Fedorov and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 101–117, doi:10.3762/bjoc.20.11

• a change of the DNA structure or occupy binding sites of essential enzymes, which in turn may influence or even inhibit important biochemical processes, for example DNA replication or transcription [1][2]. As a result, the development of DNA-targeting drugs still involves the design of suitable DNA

• intercalators, and some currently applied anticancer drugs actually operate on the basis of intercalation [3]. Hence, several classes of compounds have been established, whose DNA-binding properties can be tailored and fine-tuned for that purpose, for example anthracyclines [5], indolocarbazoles [6], acridines

• -inflammatory drugs [18]. In this context, the benzo[c]quinolizinium structure provides some special features. First of all, it has the general requirements of a DNA intercalator, namely a planar, polycyclic heteroaromatic structure and a permanent positive charge [14]. Moreover, it has been shown that this DNA

Synthesis of N-acyl carbazoles, phenoxazines and acridines from cyclic diaryliodonium salts

• Nils Clamor,
• Mattis Damrath,
• Thomas J. Kuczmera,
• Daniel Duvinage and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 12–16, doi:10.3762/bjoc.20.2

• fluorophors, previously shown to exhibit strong organic phosphorescence when mixed with specific additives [1][2][3][4][5]. Carbazole units are also found in drugs and natural products. They are also used in electrochemistry and as reagents in transamidation reactions [6][7][8][9][10][11][12]. The traditional

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• strategies is cereblon (CRBN), the target focus of a collection of immunomodulatory drugs containing the glutarimide moiety such as thalidomide, pomalidomide, lenalidomide [12][13], and avadomide [14] (Figure 1). These ligands, although prevalent recruiters in PROTAC design, present several drawbacks

• , resulting in glutarimides with a heterocyclic fragment at the α-position 1a–e – structures in demand for the design of CRBN ligands and immunomodulatory drugs. In compound 6n, catalytic hydrogenation was used to reduce the nitro group, resulting in the production of a benzotriazole analog of pomalidomide

• have been obtained. Glutarimide-based immunomodulatory drugs (IMiDs) and CRBN ligands. Examples of α-carbonyl NH-heterocycles for which N–H insertion products could not be obtained. Main literature approaches towards α-hetaryl glutarimides 1 (routes A and B) and new “diazo” methodology based on Rh(II

A novel recyclable organocatalyst for the gram-scale enantioselective synthesis of (S)-baclofen

• Gyula Dargó,
• Dóra Erdélyi,
• Balázs Molnár,
• Péter Kisszékelyi,
• Zsófia Garádi and
• József Kupai

Beilstein J. Org. Chem. 2023, 19, 1811–1824, doi:10.3762/bjoc.19.133

• organocatalysts has been a major breakthrough in the realization of enantioselective transformations. Stereoselective synthesis is essential in the pharmaceutical industry, as the development of drugs often requires the production of enantiomerically pure chiral compounds [6][7][8]. The application of

• reaction could be used in the synthesis of several drugs to form a carbon–carbon bond in a stereoselective manner [6][35]. Our goal was to synthesize the chiral precursor 17 of baclofen (Scheme 3). To achieve this objective, we first planned to use Meldrum’s acid and 4-chloro-trans-β-nitrostyrene (16

Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

• Yordanka Mollova-Sapundzhieva,
• Plamen Angelov,
• Danail Georgiev and
• Pavel Yanev

Beilstein J. Org. Chem. 2023, 19, 1804–1810, doi:10.3762/bjoc.19.132

• ], drugs used to treat cystic fibrosis and HIV infection, respectively. A plethora of 4-quinolones with various substitution patterns and biological activities have been isolated from natural sources. This includes plant-derived alkaloids such as graveoline [7], evocarpine [8], leiokinine [9], evollionine

• extensively studied is 2-heptyl-4-quinolone (HHQ) and its oxygenated derivatives 2-heptyl-3-hydroxy-4-quionolone (PQS) and 4-hydroxy-2-heptylquinoline-N-oxide (HQNO) [27][36][37][38]. Considering the importance of 4-quinolones as potential drugs and biological probes, it is not surprising that the development