Natural and synthetic 5-(3'-indolyl)oxazoles: Biological activity, chemical synthesis and advanced molecules.

5-(3'-Indolyl)oxazole moiety is a privileged heterocyclic scaffold, embedded in many biologically interesting natural products and potential therapeutic agents. Compounds containing this scaffold, whether from natural sources or synthesized, have demonstrated a wide array of biological activities. This has piqued the interest of synthetic chemists, leading to a large number of reported synthetic approaches to 5-(3'-indolyl)oxazole scaffold in recent years. In this review, we comprehensively overviewed the different biological activities and chemical synthetic methods for the 5-(3'-indolyl)oxazole scaffold reported in the literatures from 1963 to 2024. The focus of this study is to highlight the significance of 5-(3'-indolyl)oxazole derivatives as the lead compounds for the lead discovery of anticancer, pesticidal, antimicrobial, antiviral, antioxidant and anti-inflammatory agents, to summarize the synthetic methods for the 5-(3'-indolyl)oxazole scaffold. In addition, the reported mechanism of action of 5-(3'-indolyl)oxazoles and advanced molecules studied in animal models are also reviewed. Furthermore, this review offers perspectives on how 5-(3'-indolyl)oxazole scaffold as a privileged structure might be exploited in the future.

Detection and Identification of Nitrile Compounds via Recognition-Enabled Chromatographic 19F NMR.

The surge in applications of nitrile compounds across diverse fields, such as pharmaceuticals, agrochemicals, dyes, and functional materials, necessitates the development of rapid and efficient detection and identification methods. In this study, we introduce a chemosensing strategy employing a novel 19F-labeled probe, facilitating swift and accurate analysis of a broad spectrum of nitrile-containing analytes. This approach leverages the reversible interaction between the 19F-labeled probe and the analytes to produce chromatogram-like outputs, ensuring the precise identification of various pharmaceuticals and pesticides within complex matrices. Additionally, this dynamic system offers a versatile platform to investigate through-space 19F-19F interactions, showcasing its potential for future applications in mechanistic studies.

NMR-Based Chiral Discrimination of Bulky Amines with a 19F-Tagged NNO Pincer Complex.

Within pharmaceutical research, ensuring the enantiomeric purity of chiral compounds is critical. Specifically, chiral amines are a crucial category of compounds, due to their extensive therapeutic uses. However, the enantiomeric analysis of these compounds, particularly those with significant steric hindrance, remains a challenge. To address this issue, our research introduces a novel chiral 19F-tagged NNO palladium pincer probe, strategically engineered with an open binding site to accommodate bulky amines. This probe facilitates the enantiodifferentiation of such amines, as evidenced by the distinct 19F NMR signals generated by the enantiomers. Moreover, our findings highlight the probe's applicability in the chiral discrimination of various psychoactive substances, underscoring its potential for the identification of illegal stimulant use and contributing to forensic investigations.

Electron Donor-Acceptor Complex Driven Photocatalyst-Free Trifluoromethylation of Heterocycles.

Heterocyclic trifluoromethylation is efficiently initiated through a photochemical reaction utilizing an electron donor-acceptor (EDA) complex, proceeding smoothly without the use of photocatalysts, transition-metal catalysts, or additional oxidants. This method has been optimized through extensive experimentation, demonstrating its versatility and efficacy across various substrates, including quinoxalinones, coumarins, and indolones. Notably, this approach enables the practical synthesis of trifluoromethylated quinoxalinones on a gram scale. Mechanistic investigations that incorporate radical trapping and ultraviolet/visible spectroscopy, confirmed the formation of the an EDA complex and elucidated the reaction pathways. This study highlights the crucial role of EDA photoactivation in trifluoromethylation, significantly expanding the application scope of EDA complexes in chemical synthesis.

An unexpected role of EasDaf: catalyzing the conversion of chanoclavine aldehyde to chanoclavine acid.

Ergot alkaloids (EAs) are a diverse group of indole alkaloids known for their complex structures, significant pharmacological effects, and toxicity to plants. The biosynthesis of these compounds begins with chanoclavine-I aldehyde (CC aldehyde, 2), an important intermediate produced by the enzyme EasDaf or its counterpart FgaDH from chanoclavine-I (CC, 1). However, how CC aldehyde 2 is converted to chanoclavine-I acid (CC acid, 3), first isolated from Ipomoea violacea several decades ago, is still unclear. In this study, we provide in vitro biochemical evidence showing that EasDaf not only converts CC 1 to CC aldehyde 2 but also directly transforms CC 1 into CC acid 3 through two sequential oxidations. Molecular docking and site-directed mutagenesis experiments confirmed the crucial role of two amino acids, Y166 and S153, within the active site, which suggests that Y166 acts as a general base for hydride transfer, while S153 facilitates proton transfer, thereby increasing the acidity of the reaction. KEY POINTS: • EAs possess complicated skeletons and are widely used in several clinical diseases • EasDaf belongs to the short-chain dehydrogenases/reductases (SDRs) and converted CC or CC aldehyde to CC acid • The catalytic mechanism of EasDaf for dehydrogenation was analyzed by molecular docking and site mutations.

Anti-inflammatory Steroids from the South China Sea Sponge Spongia officinalis.

One new highly degraded steroid, namely 21-nor-4-ene-chaxine A (1) furnishing a 5/6/5-tricyclic, along with one known related analogue (2), were isolated from the South China Sea sponge Spongia officinalis. Their structures including absolute configurations were established by extensive spectroscopic data analysis, TDDFT-ECD calculation, and comparison with the spectral data previously reported in the literature. Compound 1 represent the new member of incisterols family with a highly degradation in ring B. In vitro bioassays revealed compound 2 exhibited significant anti-microglial inflammatory effect on lipopolysaccharide (LPS)-induced inflammation in BV-2 microglial cells.

Two Undescribed Coumarins from Notopterygium Incisum with Anti-Inflammatory Activity.

Two previously undescribed coumarins (1-2) were isolated from the root of Notopterygium incisum. The structures of new findings were elucidated by analyses of spectral evidences in HRESIMS, NMR, as well as ICD. The absolute configurations were further confirmed by chemical calculations. 1-2 exhibits obviously anti-inflammatory activity by inhibiting the expression of inflammatory mediators (COX-2, iNOS), as well as reducing the release of NO and the accumulation of ROS in cells. Western blotting analysis revealed that 2 could inhibit the PI3K/AKT pathway by reducing the expression of p-PI3K and p-AKT.

Secondary metabolites isolated from Trichoderma hamatum b-3 and their fungicidal activity.

An undescribed trichodenone derivative (1), two new diketopiperazines (3 and 4) along with a bisabolane analog (2) were isolated from Trichoderma hamatum b-3. The structures of the new findings were established through comprehensive analyses of spectral evidences in HRESIMS, 1D and 2D NMR, Marfey's analysis as well as comparisons of ECD. The absolute configuration of 2 was unambiguously confirmed by NMR, ECD calculation and Mo2(AcO)4 induced circular dichroism. Compounds 1-4 were tested for their fungicidal effects against eight crop pathogenic fungi, among which 1 showed 51% inhibition against Sclerotinia sclerotiorum at a concentration of 50 µg/mL.

New sesquiterpenoids from the flowers of pentanema britannicum (L.) D.Gut.Larr.

Five new sesquiterpenoids, (4S, 5S, 6S, 7S, 8 R)-5,6-dihydroxy-1-acetoxy-10(14)-en-britannilactone (1), (4S, 5 R, 6S, 7S, 8 R)-5,6-dihydroxy-1-acetoxy-10(14)-en-britannilactone (2), 6-O-propionyl-britannilactone (3), 1ß-hydroxy-3α-acetoxyeudesma-11(13)-en-12,8ß-olide (4) and 1ß,5ß-dihydroxyeudesma-11(13)-en-12,8ß-olide (5), along with twelve known ones were isolated from the flowers of Pentanema britannicum (L.) D.Gut.Larr. Among them, compounds 1 and 2 were stereoisomers which belong to 1,10-seco-eudesmane sesquiterpenoid with rare double bond between C-10 and C-14. The structures of the isolated compounds were elucidated by various spectroscopic methods, including 1D and 2D NMR experiments.