Isolation of four new monoterpenes from Ailanthus altissima (mill.) Swingle and their enzyme inhibitory effects.

A phytochemical study of the ethanol extract from Ailanthus altissima (Mill.) Swingle leaves resulted in the isolation of four new monoterpenoids (1-3, 5). The structures were elucidated using HRESIMS data, NMR spectroscopic data, quantum chemical calculations for NMR and ECD, and custom DP4+ probability analysis. Additionally, the absolute configuration of sugar was determined by acid hydrolysis. Compounds 1-4 are cyclogeraniane monocyclic monoterpenes, while compound 5 contains an acyclic mycrane monoterpenes skeleton. Anti-tyrosinase, anti-acetylcholinesterase, and anti-butyrylcholinesterase activities were tested. Compound 1 showed notable anti-acetylcholinesterase activity, and compound 3 exhibited significant inhibitory effects on anti-tyrosinase activity. Furthermore, the potential binding sites of compounds 1 and 3 were predicted by molecular docking.

Bioassay-Guided and DeepSAT-Driven Precise Mining of Monoterpenoid Coumarin Derivatives with Antifeedant Effects from the Leaves of Ailanthus altissima.

Demand for the exploration of botanical pesticides continues to increase due to the detrimental effects of synthetic chemicals on human health and the environment and the development of resistance by pests. Under the guidance of a bioactivity-guided approach and HSQC-based DeepSAT, 16 coumarin derivatives were discovered from the leaves of Ailanthus altissima (Mill.) Swingle, including seven undescribed monoterpenoid coumarins, three undescribed monoterpenoid phenylpropanoids, and two new coumarin derivatives. The structure and configurations of these compounds were established and validated via extensive spectroscopic analysis, acetonide analysis, and quantum chemical calculations. Biologically, 5 exhibited significant antifeedant activity toward the Plutella xylostella. Moreover, tyrosinase being closely related to the growth and development of larva, the inhibitory potentials of 5 against tyrosinase was evaluated in vitro and in silico. The bioactivity evaluation results highlight the prospect of 5 as a novel category of botanical insecticide.

Two pairs of bioactive cyclohexene alkaloid enantiomers from the roots of Piper nigrum.

Two pairs of cyclohexene amide alkaloid enantiomers were obtained from the root of Piper nigrum. Their plane structures were established by NMR and HRESIMS spectra. The absolute configurations of 1a/1b and 2a/2b were determined by the comparison between the experimental and calculated electronic circular dichroism (ECD) spectra. All identified compounds were tested for inhibitory effects on acetylcholinesterase (AChE) in vitro. Notably, compounds 1b and 2b showed strong inhibitory effects on AChE and the interaction between proteins and compounds was discussed by molecular docking studies.

Structurally diverse 1,2-diarylpropanes from the fruit of Crataegus pinnatifida and the investigation on their mirror-image ECD spectra with the same absolute configurations.

1,2-diarylpropanes are a kind of abundant natural products formed by radical coupling. On account of molecular flexibility, it was challenged in the identifications of relative and absolute configurations of the 1,2-diarylpropanes. In this research, fourteen pairs of enantiomeric 1,2-diarylpropanes (1a/1b-14a/14b), comprising twelve previously undescribed pairs (1a/1b-4a/4b, 6a/6b-10a/10b, and 12a/12b-14a/14b), were isolated from the fruit of Crataegus pinnatifida. Their structures were determined through multiple NMR spectral analyses, empirical NMR rules, X-ray crystallography, and the comparison of experimental ECD spectra with calculated data. In addition, the analysis of ECD spectra revealed that substituent effects could generate an inverted chiroptical response, exhibiting in mirror-image ECD signals. This phenomenon was investigated by conformational analysis, molecular orbital analysis, the transition density matrix and hole/electron distributions. Moreover, a potential experimental rule was proposed for the rapid determination of the absolute configurations of the 1,2-diarylpropanes.

Target isolation of diverse sesquiterpenoid from the stems of Daphne genkwa based on molecular networking.

Guiding by LC-MS/MS analysis and the Global Natural Products Social (GNPS) Molecular Networking, three undescribed sesquiterpenoids, stedapgens A-C, and two known analogues were discovered in the barks of Daphne genkwa Sieb. et Zucc. The structures were determined by analysis of their spectroscopic data and quantum-chemical calculations. All the isolated novel compounds were tested for their acetylcholinesterase inhibitory activities with IC50 = 0.754 ± 0.059, 0.696 ± 0.026, and 0.337 ± 0.023 µg/ml. Among them, stedapgen A displayed promising inhibitory activities against AChE, and the binding sites were predicted by molecular docking.

Diffusion-induced lithium isotopic heterogeneity in olivines from peridotites of an oceanized mantle lithosphere at the Yunzhug ophiolite (central Tibet).

This paper reports lithium concentrations and isotopic compositions of olivines in the oceanized subcontinental lithospheric mantle (SCLM) peridotites of the Tibetan Yunzhug ophiolite. The results show systematic Li isotope changes with distance from the rim of olivine grains. δ7Li values of olivine in dunites decrease from + 10.46 to + 1.33‰ with increasing distance to olivine rim from 26.15 to 124.71 µm. A negative correlation of δ7Li and Li content in olivine from dunite and harzburgite indicates recent diffusive ingress of Li into the peridotites. The extremely heavy Li isotopic composition requires the seawater or seawater alteration endmember in the mixing model, and reveals Li diffusion from seawater into olivine. As in dunites, olivines in a harzburgite sample show similar variations in δ7Li as a function of distance from the grain rim (e.g., 6.01 to 1.73 in sample 14YZ13). We suggest that the behavior of Li in the oceanized SCLM peridotites may be controlled by Li diffusion from seawater, as Li activity in the liquid state is higher than the solid state in transporting Li through the olivines in the peridotites. This study supports that seawater Li diffusion is one of the important factors for the heterogeneity of mantle Li isotopes in ophiolites.

Eight structurally diverse components with anti-acetylcholinesterase activity from Daphne bholua.

Eight structurally diverse components, including six undescribed ones, (±)-daphuarin A (1a/1b), daphuarin B (2), daphuarin D-E (4-6), together with a pair of new natural products (±)-daphuarin C (3a/3b) were isolated from the herb of Daphne bholua Buch.-Ham. ex D. Don. Their planar structures were elucidated by extensive spectroscopic analyses. The configurations were established with the assistance of quantum chemical calculations, together with the Custom DP4+ method. The inhibitory potentials of all isolates against acetylcholinesterase were evaluated.

Isolation and characterization of seven neovibsane-type diterpenoids from Viburnum odoratissimum and their neuroblastoma cell protective effects.

Seven undescribed neovibsane-type diterpenoids (1-7) were isolated from the leaves of Viburnum odoratissimum. Their planar structures and relative configurations were elucidated based on a combination of 1D and 2D NMR analysis. The absolute configurations were confirmed by Rh2(OCOCF3)4-induced ECD analysis and comparison of experimental and TDDFT-calculated ECD spectrum. Based on the empirical results of the ECD of in situ formed Rh-complexes, rapid determination of the absolute configuration of C-14 within vibsane-type diterpenoids was proposed. In addition, 3 exhibited a high neuroblastoma cell protective effect of 81.8 % at 50 µM (the control group showed a neuroblastoma cell protective effect of 56.2 % at 50 µM).

Molecular properties, structure and chiral resolution of secondary metabolites from the leaves of Viburnum chingii.

A chemical investigation of leaves of Viburnum chingii afforded eleven compounds, including one undescribed lignan (1), a pair of known phenylpropanoid enantiomers (2a/2b), and eight known lignans (3-10). Their structures were elucidated by detailed spectroscopic and comparative literature data analysis. The absolute configurations of compounds 1 was determined by comparing the experimental ECD data with the calculated values. The compounds 2a/2b were separated successfully by a chiral chromatographic column. In addition, the acetylcholinesterase (AChE) inhibitory activities of described compounds were evaluated.

Expanded Application of Piper nigrum: Guided Isolation of Alkaloids with Inhibitory Activities of AChE/BuChE and Aß Aggregation.

Piper nigrum is a popular crop that can be used as seasoning or as an additive but its active ingredients also have an effect on the nervous system. Nineteen new amide alkaloids (1a/1b, 2-5, 6a/6b, 7, 8a/8b, 9, 10a/10b, 11a-11b, 12-14) were isolated from P. nigrum, guided by inhibitory activity of AChE and LC-MS/MS based on GNPS. The configurations were determined by extensive spectral analysis, Bulkiness rule, and NMR calculations. The inhibitory activities of AChE/BuChE and Aß aggregation were tested, and the results showed compounds 2, 7, and 12 had significant inhibitory activities. These components were identified in the crude fraction and their relative quantities were tested, which suggested that compound 2 was the index component in the active site from P. nigrum.

Six undescribed guaianolide-type sesquiterpenes from the aerial parts of Daphne penicillata.

Six undescribed guaianolide sesquiterpenes (1-6) were obtained from the aerial parts of Daphne penicillata. Their structures and absolute configuration were elucidated by HRESIMS, NMR analyses, ECD calculations and single-crystal X-ray diffraction analysis. Structurally, all compounds possess the typical 5,7-fused system of 8,12-guaianolides and this guaianolide-type was first reported to be isolated from Daphne penicillata. All compounds (1-6) were evaluated for anti-inflammatory and cytotoxic activity. Among them, compounds 1 and 5 showed moderate inhibitory effects on LPS-induced NO production in BV2 cells and 4 displayed potential inhibition against Hep3B cells with an IC50 value of 7.33 µM.

Aromatic glycosides and lignans glycosides with their acetylcholinesterase inhibitory activities from the leaves of Picrasma quassioides.

In this study, eight new natural products were isolated from the leaves of Picrasma quassioides. Spectroscopic techniques were used for the elucidation of their planar structures. Their absolute configurations were elucidated on the basis of electron circular dichroism (ECD) techniques combined with the P/M helicity rule for the 2,3-dihydrobenzofuran chromophore, and saccharide hydrolysis. Cholinesterase inhibitors are often used as Alzheimer's disease inhibitors.Thus, acetylcholinesterase and butyrylcholinesterase inhibitory activity of these eight compounds were tested, and results showed that only compound 6 showed weakly acetylcholinesterase inhibitory activity. In particular, molecular docking was used to illustrate the bindings between compound 6 and the active sites of AChE.

Four pairs of neolignan enantiomers with distinctive isochroman moiety from the fruits of Crataegus pinnatifida and their protective activities against H2O2-induced SH-SY5Y cells.

Four pairs of neolignan enantiomers (±)-1- (±)-4 with a distinctive isochroman moiety, including seven undescribed compounds, were isolated and identified from the fruits of Crataegus pinnatifida. Structural characterization of these compounds was established through comprehensive spectroscopic analyses, as well as quantum chemical calculations of ECD and NMR data. The preliminary bioassay displayed that compounds (+)-2 and (±)-3 exerted protective activities against H2O2-induced human neuroblastoma SH-SY5Y cells compared with the positive control. These bioactive compounds could be potential candidates for further pharmaceutical applications.

Structurally diverse rearranged sesquiterpenoids, including a pair of rare tautomers, from the aerial parts of Daphne penicillata.

Eight structurally diverse rearranged sesquiterpenoids, including seven undescribed sesquiterpenoids (1a/1b and 3-8) were obtained from the aerial parts of Daphne penicillata. 1a/1b, 3, 5 and 6 possess rare rearranged guaiane skeletons and 4 represents the first example of rearranged carotene sesquiterpenoids. Their structures and absolute configurations were determined by extensive spectroscopic analyses, NMR and ECD calculations. Interestingly, 1a and 1b were a pair of magical interconverting epimers that may interconvert by retro-aldol condensation. The mechanism of interconversion has been demonstrated indirectly by 9-OH derivatization of 1a/1b and a hypothetical biogenetic pathway was proposed. All compounds were evaluated for anti-inflammatory and cytotoxic activities. Among them, 1a/1b and 2 exhibited potential inhibitory activities on the production of NO against LPS-induced BV2 microglial cells.

Structurally diverse terpenoids from Elephantopus scaber L. and their acetylcholinesterase inhibitory activities.

Three undescribed compounds elephantopuscabers A-C, along with one previously reported compound spirowallichiione, were isolated from Elephantopus scaber L. Their structures were determined via extensive NMR spectroscopic analysis, quantum chemical calculations, and single-crystal X-ray diffraction crystallography. A plausible biosynthetic pathway for spirowallichiione was proposed. All the isolated compounds were tested for their acetylcholinesterase inhibitory activities. Among them, elephantopuscaber B and C displayed promising inhibitory activities against AChE, and the binding sites were predicted by molecular docking.

Discovery of Michael reaction acceptors from the leaves of Ailanthus altissima by a modified tactic.

Structural characteristics-guided investigation of Ailanthus altissima (Mill.) Swingle resulted in the isolation and identification of seven undescribed potential Michael reaction acceptors (1-7). Ailanlactone A (1) possesses an unusual 1,7-epoxy-11,12-seco quassinoid core. Ailanterpene B (6) was a rare guaianolide-type sesquiterpene with a 5/6/6/6-fused skeleton. Their structures were determined through extensive analysis of physiochemical and spectroscopic data, quantum chemical calculations, and single crystal X-ray crystallographic technology using Cu Kα radiation. The cytotoxic activities of isolates on HepG2 and Hep3B cells were evaluated in vitro. Encouragingly, ailanaltiolide K (4) showed significant cytotoxicity against Hep3B cells with IC50 values of 1.41 ± 0.21 µM, whose covalent binding mode was uncovered in silico.

Stereochemical insights into structurally diverse lignanamides from the herbs of Solanum lyratum Thunb.

A chemical investigation of Solanum lyratum Thunb. (Solanaceae) afforded six pairs of enantiomeric lignanamides consisting of twelve undescribed compounds, along with two undescribed racemic mixtures, and the separations of the enantiomers were accomplished by chiral-phase HPLC. The structures of these undescribed compounds were elucidated by the analysis of spectroscopic data, NMR and electronic circular dichroism calculations. All isolated compounds were assessed for neuroprotective activities in H2O2-induced human neuroblastoma SH-SY5Y cells, and acetylcholinesterase (AChE) inhibitory activities. Among tested isolates, some enantiomeric lignanamides exhibited conspicuous neuroprotective effects and AChE inhibitory effect.

Four Pairs of Neuroprotective Aryldihydronaphthalene-Type Lignanamide Enantiomers from the Herbs of Solanum lyratum.

Four pairs of aryldihydronaphthalene-type lignanamide enantiomers were isolated from Solanum lyratum (Solanaceae). The enantiomeric separation was accomplished by chiral-phase HPLC, and five undescribed compounds were elucidated. Analysis by various spectroscopy and ECD calculations, the structures of undescribed compounds were illuminated. The neuroprotective effects of all compounds were evaluated using H2 O2 -induced human neuroblastoma SH-SY5Y cells and AchE inhibition activity. Among them, compound 4 a exhibited remarkable neuroprotective effects at high concentrations of 25 and 50 µmol/L comparable to Trolox. Compound 1 a showed the highest AchE inhibition with the IC50 value of 3.06±2.40 µmol/L. Molecular docking of the three active compounds was performed and the linkage between the compounds and the active site of AchE was elucidated.

Discovery of the Caged-Vibsane Norditerpenoids with Unprecedented Chemical Architectures and Exploration of Their Various Acid Tolerances.

Cyclovibsanones A-D (1-4, respectively), featuring unprecedented caged tricyclo[5.4.1.05,9]dodecane and bicyclo[4.2.1]hexane cores, were isolated from the leaves of Viburnum odoratissimum. Their structures as well as that of one chemical derivative (5), which was transformed from 2, were determined by spectroscopic data, theoretical calculations, and the ML-JDP4/MAEΔΔδ methods. In addition, compounds 1 and 2 were found to possess dissimilarities in acid tolerance during nuclear magnetic resonance (NMR) experiments. The potential mechanism was consequently postulated and further supported through NMR analysis and mechanistic calculations. Biologically, chemical derivative 5 exerted antiproliferative activity against HepG2 cells.

Rapid determination of the relative configuration of diverse 8,4'-oxyneolignans by NMR analysis: Retrospective studies, improvement and structural revision.

The characteristic 1H NMR signals (H-7 and H2-9) are significant parameters that have been widely used to assess the relative configuration of H-7 and H-8 of 8,4'-oxyneolignans. However, many usual 8,4'-oxyneolignans cannot be accurately determined by existing NMR methods and no research considering their limitations was performed until now. In this study, the application scope of NMR methods was comprehensively studied and the ΔδH9a-H9b methods have been extended to solve the majority of configuration determination difficulties. The accuracy of extended NMR methods was verified by anisotropic NMR (RCSA measurements), NMR calculation and diverse statistical analysis (MAEΔΔδ, CP3 and DP4+). Furthermore, the theoretical conformational analysis was performed to investigate the inherent limitations of existing NMR methods. This study could provide a valuable reference for determining the relative configuration of H-7 and H-8 in 8,4'-oxyneolignans and the relative configuration of 23 recently reported 8,4'-oxyneolignan derivatives should be reassigned as well.