A Diels–Alder probe for discovery of natural products containing furan moieties

• Alyssa S. Eggly,
• Namuunzul Otgontseren,
• Carson B. Roberts,
• Amir Y. Alwali,
• Haylie E. Hennigan and
• Elizabeth I. Parkinson

Beilstein J. Org. Chem. 2024, 20, 1001–1010, doi:10.3762/bjoc.20.88

• , natural products containing furan moieties (Figure 1A) are of interest as they have shown promising biological activities. One well-studied example is the antifungal flufuran, which was isolated from Aspergillus flavus [2]. Another example is plakorsin D, an anticancer polyketide natural product which was

• utilizing the probe in additional strains to probe for novel natural products similar to the MMFs. A) Bioactive natural products containing a furan ring (blue) or 3-furoic acid moiety (red): plakorsin D, wortmannin, tournefolin C, rosefuran, and flufuran and their respective biological activities. B) MMF

Enhancing structural diversity of terpenoids by multisubstrate terpene synthases

• Min Li and
• Hui Tao

Beilstein J. Org. Chem. 2024, 20, 959–972, doi:10.3762/bjoc.20.86

• terpenoids with diverse cyclic structures and important biological activities, which are of great interest. However, the number of known fungal MSTSs is currently limited, and researchers have focused on the promiscuity of their products rather than substrates [25][26][27]. Unlike plant MSTSs, fungal MSTSs

• been utilized. New building blocks with irregular carbon numbers broaden the diversity of terpenoid structures. However, more systematic studies on noncanonical terpenoids are needed to study their biological activities. Biosynthetic pathway of terpenoids. Valuable terpenoids, noncanonical C11 and C16

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

• , 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

• approach will allow direct access to ready to screen molecular scaffolds for medicinal chemistry programs to investigate different biological activities [16][17][18]. Motivated by the shortcomings of current methodologies and the absence of a tetrazole building block approach, we have pursued and report

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

• schistosomiasis [22][23][24][25]. The combination of the privileged heterocycles tetrazole and tetrahydroisoquinoline in one molecule generates new molecules which could have biological activities. A standard Ugi four-component reaction (Ugi-4CR) of an aldehyde, amine, isocyanide, and a carboxylic acid produces

Discovery and biosynthesis of bacterial drimane-type sesquiterpenoids from Streptomyces clavuligerus

• Dongxu Zhang,
• Wenyu Du,
• Xingming Pan,
• Xiaoxu Lin,
• Fang-Ru Li,
• Qingling Wang,
• Qian Yang,
• Hui-Min Xu and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2024, 20, 815–822, doi:10.3762/bjoc.20.73

• these, drimane-type sesquiterpenoids (DMTs) are distinct due to their chemical structures, which feature a decahydronaphthalene core adorned with methyl groups, mirroring the A/B rings found in labdane-derived diterpenoids [5][6] (Figure 1a). DMTs exhibit significant biological activities, such as those

• emphasize the potential of DMTs as substances with broad and significant biological activities. The biosynthetic pathways for DMTs, especially for calidoustene C, (+)-isoantrocin, and (−)-antrocin, have been extensively elucidated [6][13][14][15][16][17][18][19][20] (Figure 1b). In the biosynthesis of

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• C60 [17][18]. By either chemical functionalization or complexation of the fullerene core, a number of biocompatible fullerene materials with interesting biological activities were recently prepared and reported [19][20][21][22][23][24]. We have reported water-soluble complexes of C60 with a nontoxic

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

• was determined by total synthesis. The biological activities of these maniwamycins were also evaluated, and they showed antiviral activity against influenza (H1N1) virus and the causative agent of COVID-19, SARS-CoV-2. This was the first report of such activity for a natural product having an azoxy

Substrate specificity of a ketosynthase domain involved in bacillaene biosynthesis

• Zhiyong Yin and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2024, 20, 734–740, doi:10.3762/bjoc.20.67

• are a large class of natural products which often exhibit potent biological activities for their application in medicine, e.g., as antibiotics or immunosuppressants [1]. Despite their high structural variability all compounds from this class are commonly made through the action of polyketide synthases

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

• into a Cosmosil 5C18-MS-II column (10 mm ID × 250 mm, Nacalai Tesque) attached to an HPLC with an autosampler, at a flow rate of 0.8 mL/min at 40 °C. Each analysis was performed using an aqueous acetonitrile mobile phase. Biological activities of variochelins Assays for all compounds were performed in

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

• : aromatic nucleophilic substitution; azide–tetrazole equilibrium; 4-azido-2-sulfonylquinazolines; quinazolines; sulfonyl group dance; Introduction The quinazoline core is a privileged structure with a wide range of applications. Quinazoline derivatives exhibit a broad spectrum of biological activities

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

• a challenge. In addition, many studies show that unsaturated AAs exhibit a variety of unique biological activities [21][22][23][24]. Accordingly, the development of efficient methods to synthesize unsaturated γ- and ε-AA derivatives is a highly sought-after target to enrich non-natural AA chemistry

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

• pathway; their non-terpenoid portions can be polyketides, indole, or shikimate-derived compounds [1][2][3]. Their hybrid nature significantly contributes to their structural diversity and wide range of biological activities. Although meroterpenoids are found ubiquitously in nature, as both primary and

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

• activities. The most direct way of obtaining this nucleus is the Groebke–Blackburn–Bienaymé three-component reaction (GBB-3CR) between aminopyridines, aldehydes, and isocyanides under both Lewis and Brønsted acid catalysis. However, several catalysts for this reaction have major drawbacks such as being

• 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

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

• 25,000 [1], yet the number of isolated compounds is significantly lower, indicating the presence of many unexpressed gene clusters. This suggests a wealth of undiscovered compounds with potentially novel structures and significant biological activities. To stimulate the expression of biosynthetic gene

• by HMBC correlations from H-2/3. Furthermore, HMBC cross-peaks from H-12 to C-10, H-11 to C-9, and H-10 to C-12 indicated that the fragments are connected through C-11 and C-10, establishing the structure of compound 3. Biological activities In our bioassays, we evaluated the inhibitory activity of

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• members exhibit beneficial biological activities. This mini-review highlights recent advances in the engineered biosynthesis of meroterpenoid compounds with C15 and C20 terpenoid moieties, with the reconstruction of fungal meroterpenoid biosynthetic pathways in heterologous expression hosts and the

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

• Rare actinomycetes are excellent sources of novel bioactive compounds, since they are less explored for secondary metabolites than the more common strains of Streptomyces [19][20]. The compounds from this group often have unique structures that may exhibit novel biological activities and could be

Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

• Fumihiro Ishikawa,
• Sho Konno,
• Hideaki Kakeya and
• Genzoh Tanabe

Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39

• ; Introduction Nonribosomal peptides (NRPs) exhibit various biological activities and have been used as therapeutic agents, such as antibiotics, anticancer agents, and immunosuppressants [1]. Additionally, NRPs function as virulence factors, such as siderophores and genotoxins [2]. Therefore, inhibiting their

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

• pharmaceutical and biological activities. Among indole derivatives, bis(indolyl)methanes (BIMs) are profoundly interesting, due to their wide range of pharmaceutical properties. The most common approach involves the electrophilic substitution of various aldehydes and ketones by indoles, utilizing either protic

Discovery of unguisin J, a new cyclic peptide from Aspergillus heteromorphus CBS 117.55, and phylogeny-based bioinformatic analysis of UngA NRPS domains

• Sharmila Neupane,
• Marcelo Rodrigues de Amorim and
• Elizabeth Skellam

Beilstein J. Org. Chem. 2024, 20, 321–330, doi:10.3762/bjoc.20.32

• positions 1 (ᴅ-Ala) and 7 (GABA) are conserved but there is considerable variability at positions 2–6, including the incorporation of additional non-proteinogenic amino acids β-methylphenylalanine (βMePhe) and kynurenine (Kyn) [3][4]. So far, no significant biological activities have been reported for these

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

• ] annulation reaction; 1,2-diaza-1,3-dienes; spiro-benzosultams; 3-substituted benzoisothiazole 1,1-dioxides; Introduction Spirobenzosultams have various biological activities [1][2][3] such as antiviral, anticancer, antimicrobial, antimalarial, and antileukemia, and are widely used in the pharmaceutical

Photochromic derivatives of indigo: historical overview of development, challenges and applications

• Gökhan Kaplan,
• Zeynel Seferoğlu and
• Daria V. Berdnikova

Beilstein J. Org. Chem. 2024, 20, 228–242, doi:10.3762/bjoc.20.23

• (Figure 14). Indirubin (26) is a purple colored dye that can be found in Isatis tinctoria and Indigofera tinctoria plants along with indigo and its derivatives or can be obtained as a metabolism product of some bacteria [68]. Given to the wide range of biological activities, including anticancer and anti

Cycloaddition reactions of heterocyclic azides with 2-cyanoacetamidines as a new route to C,N-diheteroarylcarbamidines

• Pavel S. Silaichev,
• Tetyana V. Beryozkina,
• Vsevolod V. Melekhin,
• Valeriy O. Filimonov,
• Andrey N. Maslivets,
• Vladimir G. Ilkin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2024, 20, 17–24, doi:10.3762/bjoc.20.3

• synthesis of various nitrogen-containing heterocyclic compounds and have a variety of biological activities [1][2][3][4]. After the discovery of click chemistry [5][6] involving the CuAAC method of 1,2,3-triazole synthesis [7][8], there has been great interest of studing the chemical and biological

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

• [22][23][24][25][26][27]. In addition, spirooxindole is also a privileged structural scaffold, which has been recognized as key structural unit in many bioactive natural products and pharmaceuticals with broad biological activities [28][29][30]. The development of elegant synthetic methodologies for

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

Unprecedented synthesis of a 14-membered hexaazamacrocycle

• Anastasia A. Fesenko and
• Anatoly D. Shutalev

Beilstein J. Org. Chem. 2023, 19, 1728–1740, doi:10.3762/bjoc.19.126

• ., vitamin B12, chlorophyll, metalloproteins, cyclic peptides, etc). PAMs themselves and their metal complexes exhibit various useful properties [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31], particularly, they possess a wide range of biological activities and are used as contrast