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

• as anticancer, antitubercular, antibacterial, antiviral, antimalarial, antiallergic, and antihypertensive (Figure 1a) [7][10]. In addition, tetrazoles constitute a diverse range of industrial applications and are extensively used in materials, agriculture, explosives and photography [11][12]. Due to

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

• targets, making uracil very interesting for medical applications. The first modification of uracil was already synthesized in 1906 [6]. However, the medical potential of uracil was not discovered until 40 years later. One of the first antibacterial studies was carried out in 1945. The first

New variochelins from soil-isolated Variovorax sp. H002

• Jabal Rahmat Haedar,
• Aya Yoshimura and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2024, 20, 692–700, doi:10.3762/bjoc.20.63

• draft genome sequence of the H002 strain identified the variochelin biosynthetic gene cluster (var), which encodes PKS (polyketide synthase) and NRPS (non-ribosomal peptide synthetase) genes. Finally, the siderophores isolated in this study exhibited antibacterial activity against several bacteria

• ::cmR strain monitored at 210 nm (right). Antibacterial activities of variochelins A (1), B (2), C (3), and E (5) against representative Gram-negative and Gram-positive bacteria. Antibacterial activities of variochelin A (1) against some known soil-isolated plant pathogens. Supporting Information

Production of non-natural 5-methylorsellinate-derived meroterpenoids in Aspergillus oryzae

• Jia Tang,
• Yixiang Zhang and
• Yudai Matsuda

Beilstein J. Org. Chem. 2024, 20, 638–644, doi:10.3762/bjoc.20.56

• . Finally, we evaluated the antibacterial activities of the compounds obtained in this study. As a result, only compound 3 exhibited weak activity against Staphylococcus aureus ATCC 6538 and Bacillus cereus with the minimum inhibitory concentration (MIC) of 500 µg/mL, respectively. Preterretonin A, the DMOA

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

• 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

• antibiotic mycophenolic acid originally isolated by Gosio in the 1890s [2], the important antibiotic penicillin was characterized more than one decade after Fleming discovered the antibacterial activity of a Penicillium extract, and since then, Penicillium has been an important target in drug development

• . Researchers have identified numerous compounds with anticancer properties, including mycophenolic acid, brefeldin A, and wortmannin [3], as well as compounds with antibacterial properties like xestodecalactones A–C, penicifurans A, and anthraquinone-citrinin [4]. From 2010 to 2022, researchers have identified

• over 260 secondary metabolites from Penicillium [5], exhibiting not only antibacterial and anticancer activities but also potent antioxidant properties, inhibition of GSK-3β and α-glucosidase activities, and interaction with the pregnane X receptor (PXR). These compounds are categorized into

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

• activity) [16], ramariolide A (antitubercular) [17], (+)-massarinolin A (antibacterial) [18], anemonin (antiparasitic) [19], (+)-pyrenolide D (cytotoxic) [20], and (+)-crassalactone D (antitumor) [21]. Synthetic or semisynthetic spiro Δα,β-butenolides have also shown a range of biological properties

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

• activity of KR21-0001A (1) was measured using 2,2-diphenyl-1-picrylhydrazyl (DPPH) (Antioxidant Assay Kit, DOJINDO© laboratory, Japan) according to the manufacturer’s protocol. Antimicrobial activity KR21-0001A (1) was investigated for antibacterial and antifungal activities with two strains of Gram

Pseudallenes A and B, new sulfur-containing ovalicin sesquiterpenoid derivatives with antimicrobial activity from the deep-sea cold seep sediment-derived fungus Pseudallescheria boydii CS-793

• Zhen Ying,
• Xiao-Ming Li,
• Sui-Qun Yang,
• Hong-Lei Li,
• Xin Li,
• Bin-Gui Wang and
• Ling-Hong Meng

Beilstein J. Org. Chem. 2024, 20, 470–478, doi:10.3762/bjoc.20.42

• gloeosporioides, Coniothyrium diplodiella, Curvularia spicifera, Fusarium proliferatum, and Penicillium digitatum) (Table 2). In the antibacterial screening, none of the compounds displayed potent activity against the tested strains (MIC ≥ 32 μg/mL). The antifungal assays showed that compounds 1–3 exhibited

• = 1.863 mm−1, F(000) = 2136. The 65189 measurements yielded 6250 independent reflections after equivalent data were averaged. The final refinement gave R1 = 0.0317 and wR2 = 0.0848 [I > 2σ(I)]. The absolute structure parameter was 0.024(6). Antibacterial assay. The antibacterial activities against human

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

• (indolyl)methanes (BIMs), has been an area of great interest in organic chemistry, since these compounds exhibit a range of interesting biological and pharmacological properties. BIMs are naturally found in cruciferous vegetables and have been shown to be effective antifungal, antibacterial, anti

• 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

• antiviral properties. BIMs function as selective antibacterial agents against several virulent Escherichia coli (E. coli) strains, which can cause many gut and urinary tract infections. They act by damaging DNA molecules and inhibiting their replication in bacteria, while also targeting the proteins that

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

Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• motif, which is frequently found in natural products, bioactive molecules, and pharmaceuticals [1][2][3][4]. 1,2-Diazepine derivatives exhibit promising biological activities such as anticonvulsant, antibacterial, and antiproliferative effects [5][6][7][8][9][10][11][12][13]. Thus, the development of

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

• natural products of microbial origin such as HHQ and its C5-congener. Two compounds with high activity against S. aureus have been identified among the newly obtained quinolones, with MICs ≤ 3.12 and ≤ 6.25 µg/mL, respectively. Keywords: antibacterial; β-keto amides; enaminones; 4-quinolones; quorum

•  2. Yields of 2-alkyl-4-quinolones 8, prepared according to Scheme 2: Yields of 1-hydroxy-2-alkyl-4-quinolone-3-carboxamides 4, prepared according to Scheme 2. Antibacterial activity of the synthesized quinolone derivatives 4, 5, and 8. Supporting Information Supporting Information File 25: Full

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

• Pd-catalyzed Heck reaction to give products 26 in 65–78% yields (Scheme 16) [75]. The pyrrolo[2,1-a]isoquinoline core installed by this route can be found in some natural products and synthetic compounds with antitumor, antibacterial, antiviral, antioxidizing, and other biological activities (Figure

Synthesis and biological evaluation of Argemone mexicana-inspired antimicrobials

• Jessica Villegas,
• Bryce C. Ball,
• Katelyn M. Shouse,
• Caleb W. VanArragon,
• Ashley N. Wasserman,
• Hannah E. Bhakta,
• Allen G. Oliver,
• Danielle A. Orozco-Nunnelly and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2023, 19, 1511–1524, doi:10.3762/bjoc.19.108

• (five Gram-positive and four Gram-negative bacteria, and three fungi). Additionally, the crystal structures of two berberine variants are described. Several berberine variants show enhanced antibacterial activity compared to the unaltered plant-derived molecule. We also report promising preliminary

• ) protein [16][17], as well as perturbing carbohydrate metabolism to generate reactive oxygen species that damage the DNA [18], as modes of action for berberine’s antibacterial effects. The antitumor properties of berberine have been attributed to DNA binding, and in particular regulating the activity of

• telomerase and topoisomerases I and II [15][19][20]. It is evident that the effects of berberine are not tied to any single mode of action. Chelerythrine has also been shown to possess a wide variety of biological activities, such as anticancer, antibacterial, and anti-inflammatory actions [11][21][22][23

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• , various dicarbonyl compounds could be coupled with 2,4-disubstituted 3,6-dihydro-2H-pyrans (DHPs). The DHP motif is a structural component of several bioactive natural products and synthetic drugs with antioxidant, antipsychotic, antibacterial, antifungal, antiviral, and anticancer activities [106][107

Two new lanostanoid glycosides isolated from a Kenyan polypore Fomitopsis carnea

• Winnie Chemutai Sum,
• Sherif S. Ebada,
• Didsanutda Gonkhom,
• Cony Decock,
• Rémy Bertrand Teponno,
• Josphat Clement Matasyoh and
• Marc Stadler

Beilstein J. Org. Chem. 2023, 19, 1161–1169, doi:10.3762/bjoc.19.84

• effects of compound 1 and related analogues could be realized by C-3 hydrolysis. In 2010, Liu et al. also demonstrated the major role played by changes at C-16 on antibacterial effects of F. pinicola steroids [33]. The acetylation at C-16 reduced the potency compared to the corresponding congener with a

Copper-catalyzed N-arylation of amines with aryliodonium ylides in water

• Kasturi U. Nabar,
• Bhalchandra M. Bhanage and
• Sudam G. Dawande

Beilstein J. Org. Chem. 2023, 19, 1008–1014, doi:10.3762/bjoc.19.76

• metabolism, cell growth and during pregnancy, ofloxacin (III) [7], an antibacterial agent, mefenamic acid (IV) [8], an anti-inflammatory agent used to treat mild pain, linezolid (V) [9], an antibacterial agent, repaglinide (VI) [10], used to treat diabetes mellitus type 2, and tolfenamic acid (VII) [11], an

Five new sesquiterpenoids from agarwood of Aquilaria sinensis

• Hong Zhou,
• Xu-Yang Li,
• Hong-Bin Fang,
• He-Zhong Jiang and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 998–1007, doi:10.3762/bjoc.19.75

• ]. Previous studies have shown that 2-(2-phenylethyl)chromones and sesquiterpenes are the characteristic and main bioactive components of agarwood [5][6]. Various bioactivities, including neuroactive [4], gastrointestinal modulation [7], cytotoxicity [8], antibacterial [9], antifungal, acetylcholinesterase

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• antibacterial acitivity against resistant S. aureus strains. It is also an inhibitor of the enzyme peptide deformylases (PDFs). The synthesis comprised the reaction between the highly substituted hydroquinone 142 and dehydroalanine 143 in the presence of chiral phosphoric acid P7 as catalyst to prepare

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• ], antiviral [11][12], antibacterial [13][14][15], antimalarial [16][17], anti-inflammatory [18][19], anti-oxidant [20][21][22], antifungal [23][24] and antibiotic [25][26] and as enzyme inhibitors [27][28]. Several pharmaceuticals, polymers and naturally occurring compounds, including heme, chlorophyll

Intermediates and shunt products of massiliachelin biosynthesis in Massilia sp. NR 4-1

• Till Steinmetz,
• Blaise Kimbadi Lombe and
• Markus Nett

Beilstein J. Org. Chem. 2023, 19, 909–917, doi:10.3762/bjoc.19.69

• -chelating molecules, which are structurally and likely also biosynthetically linked to massiliachelin. However, these compounds are not related to the predicted lipopeptide siderophore. Herein, we describe their isolation, characterization and antibacterial activities, and we discuss their biosynthetic

• signal at δH 7.62 ppm characteristic for an amide. In vitro tests were conducted for all compounds to assess their antibacterial activities against three Gram-negative bacteria (Escherichia coli, Agrobacterium tumefaciens and Pseudomonas fluorescens) and one Gram-positive bacterium (Bacillus subtilis

• paper assay The bacterial strains were acquired from the Leibniz Institute DSMZ (German Collection of Microorganisms and Cell Cultures GmbH). To test antibacterial activity, 0.1 mL of an overnight culture of each bacterial strain was plated on agar plates containing their preferred medium. The samples

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

• tricyclic imidazonaphthyridinone derivative having antibacterial properties, with low catalyst loading (0.1 mol %) (Scheme 20b). Later, in 2014, the same authors, using an amide as directing group (DG), developed a protocol for the regioselective C3-alkenylation of pyridines through syn-addition of alkynes