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

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• , while antibacterial activity was tested against Gram-positive and Gram-negative bacteria. Unfortunately, all compounds exhibited very low activity in these assays. However, the oxathiaphospholanes were evaluated for their antifungal properties against Candida albicans and Saccharomyces cerevisiae, where

Synthesis of 4-functionalized pyrazoles via oxidative thio- or selenocyanation mediated by PhICl₂ and NH₄SCN/KSeCN

• Jialiang Wu,
• Haofeng Shi,
• Xuemin Li,
• Jiaxin He,
• Chen Zhang,
• Fengxia Sun and
• Yunfei Du

Beilstein J. Org. Chem. 2024, 20, 1453–1461, doi:10.3762/bjoc.20.128

• -inflammatory [6], antiviral [7], antibacterial [8], antifungal [9], cytotoxic [10], antioxidant [11], and analgesic [12] activities. For instance, celecoxib (I, Figure 1) (for treating rheumatoid arthritis and osteoarthritis), tepoxalin (II, Figure 1) (a veterinary painkiller used to relieve pain from muscle

Synthesis and optical properties of bis- and tris-alkynyl-2-trifluoromethylquinolines

• Stefan Jopp,
• Franziska Spruner von Mertz,
• Peter Ehlers,
• Alexander Villinger and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1246–1255, doi:10.3762/bjoc.20.107

• is applied as antimalarial agent and furthermore as a bitter flavour component. Mefloquin [5] and ciprofloxacin [6], on the other hand, are synthetic compounds containing a fluorinated quinoline and quinolone core structure and are used as antimalarial and antibacterial agents, respectively (Figure 1

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

• biological activities [1][2]. Notably, kinamycins demonstrate both antibacterial and antitumor activities, while lomaiviticin emerges as a potent antitumor agent, displaying remarkable IC50 values ranging from 0.007–72 nM against 25 cultured human cancer cell lines [3][4][5][6][7]. The pivotal 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

Mild and efficient synthesis and base-promoted rearrangement of novel isoxazolo[4,5-b]pyridines

• Vladislav V. Nikol’skiy,
• Mikhail E. Minyaev,
• Maxim A. Bastrakov and
• Alexey M. Starosotnikov

Beilstein J. Org. Chem. 2024, 20, 1069–1075, doi:10.3762/bjoc.20.94

• activity, such as antibacterial [8], anticancer [9] or antiproliferative [10]. In addition, isoxazolo[4,5-b]pyridines were found to inhibit cytochrome P450 CYP17 responsible for the biosynthesis of androgens and estrogen precursors [11]. Some biologically active isoxazolo[4,5-b]pyridines are shown on

• -oriented heterocyclic systems. Some examples of biologically active isoxazolo[4,5-b]pyridines with antibacterial [8], anticancer [12] and cytotoxic [10][13] acitivities. Biologically active analogs of compounds 13. X-ray crystal structures of compounds 12c (top left; the second crystallographically unique

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