Diterpenoids from the Aerial Parts of Isodon serra with Selective Cytotoxic Activity.

Four new diterpenoids, isodosins A-D (1-4), together with nine known compounds (5-13) were isolated and identified from the aerial parts of Isodon serra (Maxim.) Hara. The structures of the new diterpenoids were elucidated based on the analysis of HR-ESI-MS data, 1D/2D-NMR-spectroscopic data, and electronic circular dichroism (ECD) calculations. Cytotoxicities of compounds 2, 3, 5, 6, and 9 against the HepG2 and H1975 cell lines were evaluated with the MTT assay. As a result, compounds 2, 3, and 6 revealed higher levels of cytotoxicity against HepG2 cells than against H1975 cells. Moreover, compund 6 demonstrated the most efficacy in inhibiting the proliferation of HepG2 cells, with an IC50 value of 41.13 ± 3.49 µM. This effect was achieved by inducing apoptosis in a dose-dependent manner. Furthermore, the relationships between the structures and activities of these compounds are briefly discussed.

Spectral Assignment in the [3 + 2] Cycloadditions of Methyl (2E)-3-(Acridin-4-yl)-prop-2-enoate and 4-[(E)-2-Phenylethenyl]acridin with Unstable Nitrile N-Oxides.

The investigation of cycloaddition reactions involving acridine-based dipolarophiles revealed distinct regioselectivity patterns influenced mainly by the electronic factor. Specifically, the reactions of methyl-(2E)-3-(acridin-4-yl)-prop-2-enoate and 4-[(1E)-2-phenylethenyl]acridine with unstable benzonitrile N-oxides were studied. For methyl-(2E)-3-(acridin-4-yl)-prop-2-enoate, the formation of two regioisomers favoured the 5-(acridin-4-yl)-4,5-dihydro-1,2-oxazole-4-carboxylates, with remarkable exclusivity in the case of 4-methoxybenzonitrile oxide. Conversely, 4-[(1E)-2-phenylethenyl]acridine displayed reversed regioselectivity, favouring products 4-[3-(substituted phenyl)-5-phenyl-4,5-dihydro-1,2-oxazol-4-yl]acridine. Subsequent hydrolysis of isolated methyl 5-(acridin-4-yl)-3-phenyl-4,5-dihydro-1,2-oxazole-4-carboxylates resulted in the production of carboxylic acids, with nearly complete conversion. During NMR measurements of carboxylic acids in CDCl3, decarboxylation was observed, indicating the formation of a new prochiral carbon centre C-4, further confirmed by a noticeable colour change. Overall, this investigation provides valuable insights into regioselectivity in cycloaddition reactions and subsequent transformations, suggesting potential applications across diverse scientific domains.

Amazon Rainforest Hidden Volatiles-Part I: Unveiling New Compounds from Acmella oleracea (L.) R.K. Jansen Essential Oil.

Motivated by the culinary and ethnopharmacological use of Acmella oleracea (L.) R.K. Jansen, this study aimed to unveil new chemical compounds from its essential oil (EO). Acmella oleracea, known for its anesthetic and spicy properties, has been used in traditional medicine and cuisine, particularly in Northern Brazil. Through a detailed GC-MS analysis, 180 constituents were identified, including 12 tentatively identified long-chain α-keto esters of various acids. Additionally, 18 new esters were synthesized for structural verification. This research expands the known chemical diversity of A. oleracea EO, providing a basis for potential pharmacological applications. The identification of new natural products, including homologs and analogs of acmellonate, underscores the EO's rich chemical profile and its potential for novel bioproduct development.

Ionones from cigar tobacco leaves.

Phytochemical studies on cigar tobacco leaves led to the isolation of 18 ionone-type compounds, including previously undescribed cigatobanes E (1) and F (2). Additionally, compounds vomifoliol acetate (3), dehydrovomifoliol (4), 8,9-dihydromegastigmane-4,6-diene-3-one (5), 7α,8α-epoxyblumenol B (6), 3-oxoactinidol (12), and loliolide acetate (15), 4ß-hydroxy-dihydroactinidiolide (17), were found in tobacco leaves for the first time. The structural elucidation of all compounds was accomplished through rigorous spectral analysis.

The Chemistry of the Defensive Secretions of Three Species of Millipedes in the Genus Brachycybe.

Millipedes have long been known to produce a diverse array of chemical defense agents that deter predation. These compounds, or their precursors, are stored in high concentration within glands (ozadenes) and are released upon disturbance. The subterclass Colobognatha contains four orders of millipedes, all of which are known to produce terpenoid alkaloids-spare the Siphonophorida that produce terpenes. Although these compounds represent some of the most structurally-intriguing millipede-derived natural products, they are the least studied class of millipede defensive secretions. Here, we describe the chemistry of millipede defensive secretions from three species of Brachycybe: Brachycybe producta, Brachycybe petasata, and Brachycybe rosea. Chemical investigations using mass spectrometry-based metabolomics, chemical synthesis, and 2D NMR led to the identification of five alkaloids, three of which are new to the literature. All identified compounds are monoterpene alkaloids with the new compounds representing indolizidine (i.e. hydrogosodesmine) and quinolizidine alkaloids (i.e. homogosodesmine and homo-hydrogosodesmine). The chemical diversity of these compounds tracks the known species phylogeny of this genus, rather than the geographical proximity of the species. The indolizidines and quinolizidines are produced by non-sympatric sister species, B. producta and B. petasata, while deoxybuzonamine is produced by another set of non-sympatric sister species, B. rosea and Brachycybe lecontii. The fidelity between the chemical diversity and phylogeny strongly suggests that millipedes generate these complex defensive agents de novo and begins to provide insights into the evolution of their biochemical pathways.

Carbon-Based Weakly Coordinating Anions: Molecular Design, Synthesis and Applications.

Although carbanions, which are usually regarded as reactive species and powerful metalation reagents, can be stabilized through choice of the substitution pattern, they have rarely been considered for the design of weakly coordinating anions (WCA).  Here, we report on an evaluation of the potential of a series of differently substituted carbanions to serve as WCA by computational methods. This led us to the synthesize the water- and air-stable allyl anion 1 with triflyl and 3,5-bis(trifluoromethyl)phenyl (ArF) moieties, which can be isolated in high yields even on a gram-scale. Single crystal X-ray crystallography and NMR studies confirmed the weak coordination ability of the anion by showing negligible or only weak interactions with different cations. This property enabled the application of 1 in the stabilization of reactive group 14 and 15 cations. In addition to the crystallization of a phosphenium cation, the first all-carbon salt with a non-aromatic carbanion is reported, which revealed to be a convenient reagent for hydride abstraction such as from silanes. Overall, this work demonstrates the so far untapped potential of carbanions as WCA, that are accessible with a variety of different cations for various applications.

Unsaturated fatty acid, Nonacosenoic acid isolated from an endophyte Chaetomium nigricolor inhabiting the stem of Catharanthus roseus and its bioactivity.

The endophytic fungus Chaetomium nigricolor culture filtrate's hexane extract was used to identify a cytotoxic very long-chain fatty acid. Based on multiple spectroscopic investigations, the structure of the compound was predicted to be an unsaturated fatty acid, Nonacosenoic acid (NA). Using the MTT assay, the compound's cytotoxic potential was evaluated against MCF-7, A-431, U-251, and HEK-293 T cells. The compound was moderately cytotoxic to breast carcinoma cell line, MCF-7 cells and negligibly cytotoxic to non-cancerous cell line HEK-293 T cells. The compound exhibited mild cytotoxic activity against A-431 and U-251 cells. The compound also induced ROS generation and mitochondrial depolarization in MCF-7 cells when assessed via the NBT and JC-1 assays, respectively. This is the first report on the production of nonacosenoic acid from the endophytic fungus Chaetomium nigricolor and the assessment of its bioactivity.

Abietane-Type Diterpenoids from the Arils of Torreya grandis.

A chemical investigation of the arils of Torreya grandis led to the isolation of seven abietane-type diterpenoids (compounds 1-7) including three previously undescribed compounds, one unreported natural product, and three known analogs. The structures of these compounds were determined by means of spectroscopy, single-crystal X-ray diffraction, and ECD spectra. An antibacterial activity assay showed that compounds 5 and 6 had significant inhibitory effects on methicillin-resistant Staphylococcus aureus, with MIC values of 100 µM. Moreover, compounds 1, 3, 4, and 7 exhibited anti-neuroinflammatory activity in LPS-stimulated BV-2 microglia cells, with the IC50 values ranging from 38.4 to 67.9 µM.

A Fluorinated Chaperone Gives X-ray Crystal Structures of Acyclic Natural Product Derivatives up to 338 Molecular Weight.

Crystallizing molecules with long flexible chains is a challenge, making it difficult to perform X-ray crystallography. Chaperones can assist in the crystallization of compounds that do not crystallize by themselves by producing solvate crystals that contain the analyte in their three-dimensional lattices. Among the most versatile chaperones for liquid analytes are tetraaryladamantanes (TAAs), but the size of the compounds that can be encapsulated is limited, and attempts to surpass this limit with known TAAs were unsuccessful. Here we report that 1,3,5,7-tetrakis(2-fluoro-4-methoxyphenyl)adamantane (TFM) is a crystallization chaperone for acyclic molecules up to the molecular weight of phytyl acetate (338 g/mol). Encapsulation of such a large acyclic compound was achieved when the analyte was esterified and when a two-step temperature protocol was used for crystallization. Exploratory work indicates that a drop to -20 °C allows for encapsulation of squalene (Mr 411 g/mol), albeit with positional disorder of the analyte. Our X-ray crystal structures of solvates with flexible analytes shed light on how crystalline order can be imposed on large acyclic analytes. The new, fluorinated TAA gives access to crystal structures that were inaccessible thus far.

Strong antagonism of an endophyte of Fraxinus excelsior towards the ash dieback pathogen, Hymenoscyphus fraxineus, is mediated by the antifungal secondary metabolite PF1140.

Ash dieback, caused by the fungal pathogen Hymenoscyphus fraxineus (Helotiales, Ascomycota), is threatening the existence of the European ash, Fraxineus excelsior. During our search for biological control agents for this devastating disease, endophytic fungi were isolated from healthy plant tissues and co-cultivated with H. fraxineus to assess their antagonistic potential. Among the strains screened, Penicillium cf. manginii DSM 104493 most strongly inhibited the pathogen. Initially, DSM 104493 showed promise in planta as a biocontrol agent. Inoculation of DSM 104493 into axenically cultured ash seedlings greatly decreased the development of disease symptoms in seedlings infected with H. fraxineus. The fungus was thus cultivated on a larger scale in order to obtain sufficient material to identify active metabolites that accounted for the antibiosis observed in dual culture. We isolated PF1140 (1) and identified it as the main active compound in the course of a bioassay-guided isolation strategy. Furthermore, its derivative 2, the mycotoxin citreoviridin (3), three tetramic acids of the vancouverone type (4-6), and penidiamide (7) were isolated by preparative chromatography. The structures were elucidated mainly by NMR spectroscopy and high-resolution mass spectrometry (HRMS), of which compounds 2 and 6 represent novel natural products. Of the compounds tested, not only PF1140 (1) strongly inhibited H. fraxineus in an agar diffusion assay but also showed phytotoxic effects in a leaf puncture assay. Unfortunately, both the latent virulent attributes of DSM 104493 observed subsequent to these experiments in planta and the production of mycotoxins exclude strain Penicillium cf. manginii DSM 104493 from further development as a safe biocontrol agent.IMPORTANCEEnvironmentally friendly measures are urgently needed to control the causative agent of ash dieback, Hymenoscyphus fraxineus. Herein, we show that the endophyte DSM 104493 exhibits protective effects in vitro and in planta. We traced the activity of DSM 104493 to the antifungal natural product PF1140, which unfortunately also showed phytotoxic effects. Our results have important implications for understanding plant-fungal interactions mediated by secondary metabolites, not only in the context of ash dieback but also generally in plant-microbial interactions.

Neutron Instruments for Research in Coordination Chemistry.

Neutron diffraction and spectroscopy offer unique insight into structures and properties of solids and molecular materials. All neutron instruments located at the various neutron sources are distinct, even if their designs are based on similar principles, and thus, they are usually less familiar to the community than commercial X-ray diffractometers and optical spectrometers. Major neutron instruments in the USA, which are open to scientists around the world, and examples of their use in coordination chemistry research are presented here, along with a list of similar instruments at main neutron facilities in other countries. The reader may easily and quickly find from this minireview an appropriate neutron instrument for research. The instruments include single-crystal and powder diffractometers to determine structures, inelastic neutron scattering (INS) spectrometers to probe magnetic and vibrational excitations, and quasielastic neutron scattering (QENS) spectrometers to study molecular dynamics such as methyl rotation on ligands. Key and unique features of the diffraction and neutron spectroscopy that are relevant to inorganic chemistry are reviewed.

Antiviral C-geranylated flavonoids from Artocarpus communis.

Ten C-geranylated flavonoids, along with three known analogues, were isolated from the leaves of Artocarpus communis. The chemical structures of these compounds were unambiguously determined via comprehensive spectroscopic analysis, single-crystal X-ray diffraction experiments, and quantum chemical electronic circular dichroism calculations. Structurally, artocarones A-I (1-9) represent a group of unusual, highly modified C-geranylated flavonoids, in which the geranyl chain is cyclised with the ortho-hydroxy group of flavonoids to form various heterocyclic scaffolds. Notably, artocarones E and G-I (5 and 7-9) feature a 6H-benzo[c]chromene core that is hitherto undescribed in C-geranylated flavonoids. Artocarone J (10) is the first example of C-9-C-16 connected C-geranylated aurone. Meanwhile, the plausible biosynthetic pathways for these rare C-geranylated flavonoids were also proposed. Notably, compounds 1, 2, 4, 8, 11, and 12 exhibited promising in vitro inhibitory activities against respiratory syncytial virus and herpes simplex virus type 1.

Two new sesterterpenoids from Atractylodes japonica Koidz. ex Kitam.

Two new sesterterpenoids, atractylodes japonica terpenoid acid I (1) and atractylodes japonica terpenoid aldehyde I (2), were isolated from the rhizomes of Atractylodes japonica Koidz. ex Kitam together with ten known compounds (3-12). Their structures were elucidated on the basis of comprehensive spectroscopic analysis (1D/2D NMR, HRESIMS and IR). In addition, all of these isolated compounds were evaluated for their cytotoxic activities against human gastric cancer cell MGC-803 and human hepatocellular cancer cell HepG-2. Most of them exhibited moderate to weak inhibitory effects with IC50 values in the range of 25.15-88.85 µM except for 9-12.

Domain Swapping in Abiotic Foldamers.

Foldamer sequences that adopt tertiary helix-turn-helix folds mediated by helix-helix hydrogen bonding in organic solvents have been previously reported. In an attempt to create genuine abiotic quaternary structures, i.e. assemblies of tertiary structures, new sequences were prepared that possess additional hydrogen bond donors at positions that may promote an association between the tertiary folds. However, a solid state structure and extensive solution state investigations by Nuclear Magnetic Resonance (NMR) and Circular Dichroism (CD) show that, instead of forming a quaternary structure, the tertiary folds assemble into stable domain-swapped dimer motifs. Domain swapping entails a complete reorganization of the arrays of hydrogen bonds and changes in relative helix orientation and handedness that can all be rationalized.

[Two new benzoyl-sesquiterpenes from Mesona chinensis].

Mesona chinensis is a common medicinal and edible plant in the Lingnan region of China, which has extensive pharmacological activity. However, the study of its chemical constituents is not sufficient. In this study, a variety of modern chromatographic separation techniques were used to isolate two compounds from 95% ethanol extract of the grass parts of M. chinensis. Their absolute configurations were determined by ultraviolet spectroscopy(UV), infrared spectroscopy(IR), high resolution mass spectrometry(HR-ESI-MS), 1D and 2D nuclear magnetic resonance(1D NMR and 2D NMR), and single-crystal X-ray diffraction(SC-XRD). Specifically, they were two new benzoyl-sesquiterpenes and named mesonanol A and mesonanol B, respectively. The results of the pharmacological activity evaluation showed that neither of the two new compounds showed obvious antiviral and anti-inflammatory activities.

Novel Types of Phyllobilins in a Fern - Molecular Reporters of the Evolution of Chlorophyll Breakdown in the Paleozoic Era.

Breakdown of chlorophyll (Chl), as studied in angiosperms, follows the pheophorbide a oxygenase/phyllobilin (PaO/PB) pathway, furnishing linear tetrapyrroles, named phyllobilins (PBs). In an investigation with fern leaves we have discovered iso-phyllobilanones (iPBs) with an intriguingly rearranged and oxidized carbon skeleton. We report here a key second group of iPBs from the fern and on their structure analysis. Previously, these additional Chl-catabolites escaped their characterization, since they exist in aqueous media as mixtures of equilibrating isomers. However, their chemical dehydration furnished stable iPB-derivatives that allowed the delineation of the enigmatic structures and chemistry of the original natural catabolites. The structures of all fern-iPBs reflect the early core steps of a PaO/PB-type pathway and the PB-to-iPB carbon skeleton rearrangement. A striking further degradative chemical ring-cleavage was observed, proposed to consume singlet molecular oxygen (1O2). Hence, Chl-catabolites may play a novel active role in detoxifying cellular 1O2. The critical deviations from the PaO/PB pathway, found in the fern, reflect evolutionary developments of Chl-breakdown in the green plants in the Paleozoic era.

Formation, Selective Encapsulation, and Tautomerization Control of Isoindolone Utilizing Guanidinium Sulfonate Frameworks.

Herein we report the use of tetrakis (guanidinium) pyrenetetrasulfonate (G4PYR) and bis (guanidinium) 1,5-napthalene disulfonate (G2NDS) to catalyze the cyclization of 2-cyanobenzamide (1) to isoindolone (2). Moreover, we demonstrate the remarkable selectivity of these guanidinium organosulfonate hosts in encapsulating 2 over 1. By thoroughly investigating the intramolecular cyclization reaction, we determined that guanidinium and the organosulfonate moiety acts as the catalyst in this process. Additionally, 2 is selectively encapsulated, even in mixtures of other structurally similar heterocycles like indole. Furthermore, the tautomeric state of 2 (amino isoindolone (2-A) and imino isoindolinone forms (2-I)) can be controlled by utilizing different guanidinium organosulfonate frameworks.

Characterization of the structure, anti-inflammatory activity and molecular docking of a neutral polysaccharide separated from American ginseng berries.

AIM: American ginseng berries, grown in the aerial parts and harvested in August, are a potentially valuable material. The aim of the study was to analyze the specific polysaccharides in American ginseng berries, and to demonstrate the anti-inflammation effect through in vitro and in vivo experiments and molecular docking. METHODS: After deproteinization and dialysis, the extracted crude polysaccharide was separated and purified. The structure of the specific isolated polysaccharide was investigated by Fourier Transform infrared spectroscopy (FT-IR), GC-MS and nuclear magnetic resonance (NMR), and anti-inflammatory activity was evaluated using in vitro and in vivo models (Raw 264.7 cells and zebrafish). Molecular docking was used to analyze the binding capacity and interaction with cyclooxygenase-2 (COX-2). RESULTS: A novel neutral polysaccharide fraction (AGBP-A) was isolated from American ginseng berries. The structural analysis demonstrated that AGBP-A had a weight-average molecular weight (Mw) of 122,988 Da with a dispersity index (Mw/Mn) value of 1.59 and was composed of arabinose and galactose with a core structure containing →6)-Gal-(1→ residues as the backbone and a branching substitution at the C3 position. The side-chains comprised of α-L-Ara-(1→, α-L-Ara-(1→, →5)-α-L-Ara-(1→, ß-D-Gal-(1→. The results showed that it significantly decreased pro-inflammatory cytokines in the cell model. In a zebrafish model, AGBP-A reduced the massive recruitment of neutrophils to the caudal lateral line neuromast, suggesting the relief of inflammation. Molecular docking was used to analyze the combined capacity and interaction with COX-2. CONCLUSION: Our study indicated the potential efficacy of AGBP-A as a safe and valid natural anti-inflammatory component.

Unusual Stabilisation of Remarkably Bent Tetra-Cationic Tetra-radical Intermolecular Fe(III) µ-Oxo Tetranuclear Complexes.

A hitherto unknown series of air stable, π-conjugated, remarkably bent tetra-cation tetra-radical intermolecular Fe(III) µ-oxo tetranuclear complex, isolated from the dication diradical diiron(III) porphyrin dimers, has been synthesised and spectroscopically characterised along with single crystal X-ray structure determination of two such molecules. These species facilitate long-range charge/radical delocalisation through the bridge across the entire tetranuclear unit manifesting an unusually intense NIR band. Assorted spin states of Fe(III) centres are stabilised within these unique tetranuclear frameworks: terminal six-coordinate iron centres stabilise the admixed intermediate spin states while the central five-coordinate iron centres stabilise the high-spin states. Variable temperature magnetic susceptibility measurements indicated strong antiferromagnetic coupling for the Fe(III)-O-Fe(III) unit while the exchange interactions between the Fe centres and the porphyrin π-cation radicals are weaker as supported both by magnetic data and DFT calculations. The nature of orbital overlap between the SOMOs of Fe(III) and π* orbital of the porphyrin was found to rationalise the observed exchange coupling, establishing such a complex magnetic exchange in this tetranuclear model with a significant bioinorganic relevance.

Structurally diverse phthalides from fibrous roots of Ligusticum chuanxiong Hort. and their biological activities.

Falonolide A (1) and B (2), two novel polyyne hybrid phthalides resulting from unprecedented carbon skeleton polymerized by Z-ligustilide and falcarindiol, along with six new related phthalides (3-8), were isolated from Ligusticum chuanxiong Hort. Their structures were elucidated by spectroscopic analysis, computer-assisted structure elucidation (CASE) analysis, DP4+ probability analysis and electronic circular dichroism (ECD) calculations. A plausible biosynthetic pathway for 1-8 was proposed, and the production mechanism of 2 was revealed by density functional theory (DFT) method. Compounds 4 and 6 exhibited significant vasodilatory activity with EC50 of 8.00 ± 0.86 and 6.92 ± 1.02 µM, respectively. Compound 4 also displayed significant inhibitory effect of NO production with EC50 value of 8.82 ± 0.30 µM. Based on the established compounds library, structure-activity relationship analysis of phthalides was explored to provide insights into the drug development of vasodilators and anti-flammatory.