2-(2-(4-Methoxyphenyl)furo[3,2-h]quinolin-3-yl)acetic Acid

A simple and efficient protocol for the synthesis of the previously unknown 2-(2-(4-methoxyphenyl)furo[3,2-h]quinolin-3-yl)acetic acid was elaborated. The suggested method is based on the telescoped multicomponent reaction of 8-hydroxyquinoline, 4-methylglyoxal, and Meldrum’s acid. The studied process includes the initial interaction of the starting compounds in MeCN followed by intramolecular cyclization to the target product in refluxing acetic acid. The advantage of this approach is the application of readily available starting materials, atom economy, and a simple work-up procedure. The structure of the synthesized furylacetic acid derivative was proven by 1H, 13C, 2D-NMR, IR spectroscopy, and high-resolution mass spectrometry.

Insights into Cytotoxic Behavior of Lepadins and Structure Elucidation of the New Alkaloid Lepadin L from the Mediterranean Ascidian Clavelina lepadiformis

The chemical investigation of the Mediterranean ascidian Clavelina lepadiformis has led to the isolation of a new lepadin, named lepadin L, and two known metabolites belonging to the same family, lepadins A and B. The planar structure and relative configuration of the decahydroquinoline ring of lepadin L were established both by means of HR-ESIMS and by a detailed as extensive analysis of 1D and 2D NMR spectra. Moreover, microscale derivatization of the new alkaloid lepadin L was performed to assess the relative configuration of the functionalized alkyl side chain. Lepadins A, B, and L were tested for their cytotoxic activity on a panel of cancer cell lines (human melanoma [A375], human breast [MDA-MB-468], human colon adenocarcinoma [HT29], human colorectal carcinoma [HCT116], and mouse myoblast [C2C12]). Interestingly, a deeper investigation into the mechanism of action of the most cytotoxic metabolite, lepadin A, on the A375 cells has highlighted its ability to induce a strongly inhibition of cell migration, G2/M phase cell cycle arrest and a dose-dependent decrease of cell clonogenity, suggesting that it is able to impair self-renewing capacity of A375 cells.

Mono-/Bis-Alkenoic Acid Derivatives From an Endophytic Fungus Scopulariopsis candelabrum and Their Antifungal Activity

During a screening for antifungal secondary metabolites, six new mono-/bis-alkenoic acid derivatives (2–7) and one known alkenoic acid derivative (1) were isolated from an endophytic fungi Scopulariopsis candelabrum. Their chemical structures were identified by 1H-NMR, 13C-NMR, 2D NMR, and high-resolution mass spectrometry, as well as comparisons with previously reported literatures. Among them, fusariumesters C‒F (2–5) are bis-alkenoic acid derivatives dimerized by an ester bond, while acetylfusaridioic acid A (6) and fusaridioic acid D (7) are alkenoic acid monomers. All the isolates were submitted to an antifungal assay against Candida albicans and the corn pathogen Exserohilum turcicum using the filter paper agar diffusion method. As a result, only compound 1 decorating with β-lactone ring turned out to be active against these two tested fungi. The broth microdilution assay against Candida albicans showed the minimum inhibitory concentration (MIC) value of 1 to be 20 μg/ml, while the minimum inhibitory concentration value of the positive control (naystatin) was 10 μg/ml. And the half maximal inhibitory concentration (IC50) value (21.23 μg/ml) of 1 against Exserohilum turcicum was determined by analyzing its inhibition effect on the mycelial growth, using cycloheximide (IC50 = 46.70 μg/ml) as the positive control.

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

The first synthesis of 2-amino-3,4-dihydroxycyclooctane-1-carboxylic acid, methyl 6-hydroxy-9-oxo-8-oxabicyclo[5.2.1]decan-10-yl)carbamate, and 10-amino-6-hydroxy-8-oxabicyclo[5.2.1]decan-9-one starting from cis-9-azabicyclo[6.2.0]dec-6-en-10-one is described. cis-9-Azabicyclo[6.2.0]dec-6-en-10-one was transformed into the corresponding amino ester and its protected amine. Oxidation of the double bond in the N-Boc-protected methyl 2-aminocyclooct-3-ene-1-carboxylate then delivered the targeted amino acid and its derivatives. Density-functional theory (DFT) computations were used to explain the reaction mechanism for the ring opening of the epoxide and the formation of five-membered lactones. The stereochemistry of the synthesized compounds was determined by 1D and 2D NMR spectroscopy. The configuration of methyl 6-hydroxy-9-oxo-8-oxabicyclo[5.2.1]decan-10-yl)carbamate was confirmed by X-ray diffraction.

Mono- and Dimeric Xanthones with Anti-Glioma and Anti-Inflammatory Activities from the Ascidian-Derived Fungus Diaporthe sp. SYSU-MS4722

Seven new xanthones, diaporthones A−G (1−7), together with 13 known analogues, including five mono- (8−14) and six dimeric xanthones (15−20), were obtained from the ascidian-derived fungus Diaporthe sp. SYSU-MS4722. Their planar structures were established by extensive spectroscopic analyses, including 1D and 2D NMR and high-resolution mass spectrometry (HR-ESIMS). The absolute configurations of 1−7 were clearly identified by X-ray crystallographic analysis and calculation of the ECD Spectra. Compounds 15−20 showed significant anti-inflammatory activity with IC50 values between 6.3 and 8.0 μM. In addition, dimeric xanthones (15−20) showed selective cytotoxicity against T98G cell lines with IC50 values ranging from 19.5 to 78.0 μM.

Terpenoids from Glechoma hederacea var. longituba and Their Biological Activities

Glechoma hederacea var. longituba (common name: ground-ivy) has been used for the treatment of asthma, bronchitis, cholelithiasis, colds, and inflammation. In the present study, three new sesquiterpene glycosides (1–3), two new diterpene glycosides (4–5), and four known compounds (6–9) were isolated from its MeOH extract. Structure elucidation was performed for the five new compounds (1–5) using 1D and 2D NMR, HRESIMS, ECD calculation, and chemical methods. All the isolates (1–9) were assessed for their anti-neuroinflammatory activity on nitric oxide (NO) production in lipopolysaccharide (LPS)-activated BV-2 cells, nerve growth factor (NGF) secretion stimulation activity in C6 glioma cells, and cytotoxic activity against four human cancer cell lines (A549, SK-OV-3, SK-MEL-2, and HCT15). Compounds 2 and 5–7 exhibited inhibitory effects on NO production with IC50 values of 52.21, 47.90, 61.61, and 25.35 μM, respectively. Compound 5 also exhibited a significant stimulating effect on NGF secretion (122.77 ± 8.10%). Compound 9 showed potent cytotoxic activity against SK-OV-3 (IC50 3.76 μM) and SK-MEL-2 (IC50 1.48 μM) cell lines, while 7 displayed a strong cytotoxic activity against SK-MEL-2 (IC50 9.81 μM) cell line

Streptoglycerides E–H, Unsaturated Polyketides from the Marine-Derived Bacterium Streptomyces specialis and Their Anti-Inflammatory Activity

Four new streptoglycerides E–H (1–4), with a rare 6/5/5/-membered ring system, were isolated from a marine-derived actinomycete Streptomyces specialis. The structures of 1–4 were elucidated by detailed analysis of HRESIMS, 1D and 2D NMR data and ECD spectra as well as comparison of their spectroscopic data with those reported in literature. Compounds 1–4 showed significant anti-inflammatory activity by inhibiting lipopolysaccharide (LPS)-induced nitric oxide (NO) production in Raw 264.7 cells with IC50 values ranging from 3.5 to 10.9 µM. Especially, 2 suppressed mRNA expression levels of iNOS and IL-6 without cytotoxicity.

Charantoside L, A New Cucurbitane-Type Glycoside from Momordica charantia L. with α-Glucosidase Inhibitory Activities

A new cucurbitane-type glycoside (1) and two known compounds (2-3) were isolated from the ethanol extract of the fruits of Momordica charantia L. Their chemical structures were determined as (19 S,23 E)-5 β­,19-epoxy-19-methoxycucurbita-6,23-diene-3 β,25-diol 3 -O-β-D-allopyranoside (1), goyaglycoside d (2), and (19 S,23 E)-5 β,19-epoxy-19-methoxycucurbita-6,23-diene-3 β,25-diol (3) on the basis of the extensive spectroscopic methods, including 1D, 2D NMR, HRESIMS, and in comparison with the reported data. Compounds 1 to 3 were evaluated for α-glucosidase inhibitory effects. Compounds 1 and 2 showed anti α-glucosidase activity with IC50 values of 134.12 ± 11.20 and 163.17 ± 13.71 µM, respectively, compared with the positive control, acarbose, IC50 160.99 ± 14.30 μM. Compounds 2 and 3 were first isolated from plant M. charantia growing in Vietnam.

Dihydrobenzofurans and Propynylthiophenes From the Roots of Eupatorium heterophyllum

Seven new dihydrobenzofurans and 2 new propynyl thiophenes were isolated from the roots of Eupatorium heterophyllum together with 13 known compounds. The compounds were characterized using spectroscopic methods including 2D NMR, infrared, and mass spectrometric techniques. Aerial parts of this plant have been known to contain various sesquiterpenoids and displayed high chemical diversity (several compounds isolated and/or identified) among their chemical constituents depending on the collection site. Nevertheless, we found that the chemical diversity in the roots was lower than in the aerial parts.

Bacillimidazoles A−F, Imidazolium-Containing Compounds Isolated from a Marine Bacillus

Chemical investigations of a marine sponge-associated Bacillus revealed six new imidazolium-containing compounds, bacillimidazoles A–F (1–6). Previous reports of related imidazolium-containing natural products are rare. Initially unveiled by timsTOF (trapped ion mobility spectrometry) MS data, extensive HRMS and 1D and 2D NMR analyses enabled the structural elucidation of 1–6. In addition, a plausible biosynthetic pathway to bacillimidazoles is proposed based on isotopic labeling experiments and invokes the highly reactive glycolytic adduct 2,3-butanedione. Combined, the results of structure elucidation efforts, isotopic labeling studies and bioinformatics suggest that 1–6 result from a fascinating intersection of primary and secondary metabolic pathways in Bacillus sp. WMMC1349. Antimicrobial assays revealed that, of 1–6, only compound six displayed discernible antibacterial activity, despite the close structural similarities shared by all six natural products.