ECD Spectra Research Articles

Four new diastereoisomeric neolignan glycosides from the root bark of Lycium chinense Miller. and their α-glucosidase inhibitory activity

Four new diastereoisomeric neolignan glycosides (1–4) along with nine known lignan glycosides (5–13) were isolated from the root bark of Lycium chinense Mill. Their structures with absolute configurations were elucidated on the basis of NMR spectroscopy, ECD, Mo2(OAc)4-induced ECD spectra, enzymatic hydrolysis and acid hydrolysis. The isolated compounds were evaluated for their α-glucosidase inhibitory activity. Compounds 8 and 13 exhibited moderate inhibitory activities against α-glucosidase with IC50 values of 26.82 ± 2.71 and 43.14 ± 2.81 μg/mL.

Three new α-pyrone derivatives from the soil-derived fungus Penicillium herquei MA-370

Three new α-pyrone derivatives, annularins L–N (1–3), were isolated from the EtOAc extract of Penicillium herquei MA-370, a fungus obtained from the rhizospheric soil of the mangrove plant Rhizophora mucronata. The planar structures of compounds 1–3 were determined based on comprehensive spectral interpretation of the NMR and MS data. The absolute configuration of 1 was determined by X-ray crystallographic data and that of 2 was assigned by TDDFT calculations of its ECD spectrum and cotton effects comparison with those of 1. The antimicrobial activity of compounds 1–3 was evaluated.

Inhibition of Aβ aggregation by naphtho-γ-pyrone derivatives from a marine-derived fungus, Aspergillus sp. MPUC239.

Alzheimer's disease (AD) is an important human disease that mainly causes cognitive impairments. Growing evidence has shown that amyloid-β (Aβ) peptide plays a key role in AD pathogenesis in what is known as the Aβ cascade hypothesis. This hypothesis suggests the importance of suppressing Aβ aggregation and Aβ production. The latter process is governed by β-site APP Cleaving Enzyme1 (BACE1) and γ-secretase. We, therefore, focused on Aβ aggregation inhibitory activity, initially assessing numerous extracts derived from our marine-derived fungus collections. One EtOAc extract derived from an Aspergillus sp. exhibited Aβ aggregation inhibitory activity. Eleven known compounds (1-11) were isolated from CHCl3 and EtOAc extracts derived from the fungus, and the structures were identified based on MS, NMR, and ECD spectra. Compounds 2, 6, and 10 inhibited Aβ aggregation with IC50 values of 2.8, 3.9, and 8.1μM, respectively. The protective effect on SH-SY5Y cells against Aβ toxicity was also evaluated, and compounds 6 and 10 significantly alleviated Aβ toxicity. BACE1 inhibitory activity was also examined, and compounds 4, 5, 7, 10, and 11 inhibited BACE1 activity with IC50 values of 14.9, 70.0, 36.5, 28.0, and 72.8μM, respectively. These data suggest that compound 10 could be useful in AD treatment.

Ferroptosis Inhibitory Compounds from the Deep-Sea-Derived Fungus Penicillium sp. MCCC 3A00126

Two new xanthones (1 and 2) were isolated from the deep-sea-derived fungus Penicillium sp. MCCC 3A00126 along with 34 known compounds (3-36). The structures of the new compounds were established by spectroscopic data. The absolute configuration of 1 was validated by comparison of experimental and calculated ECD spectra. All isolated compounds were evaluated for cytotoxicity and ferroptosis inhibitory activities. Compounds 14 and 15 exerted potent cytotoxicity against CCRF-CEM cells, with IC50 values of 5.5 and 3.5 μM, respectively, whereas 26, 28, 33, and 34 significantly inhibited RSL3-induced ferroptosis, with EC50 values of 11.6, 7.2, 11.8, and 2.2 μM, respectively.

Alkaloids and Polyacetylenes from Hippobroma longiflora with Antiangiogenesis Properties.

Four new alkaloids, hippobrines A-D (1-4), along with three new polyacetylenes, hippobrenes A-C (5-7), were isolated from Hippobroma longiflora. Compounds 1-3 possess an unprecedented carbon skeleton. All of the new structures were determined by analyzing their mass and NMR spectroscopic data. The absolute configurations of 1 and 2 were confirmed by single-crystal X-ray analyses, and the absolute configurations of 3 and 7 were deduced using their ECD spectra. Plausible biogenetic pathways of 1 and 4 were proposed. In regard to bioactivities, all compounds (1-7) exhibited weak antiangiogenic activity against human endothelial progenitor cells, with IC50 values ranging from 21.1 ± 1.1 to 44.0 ± 2.3 μg/mL.

Secondary metabolites from the Cordyceps-colonizing fungus Aspergillus versicolor ZJUTE2

Two new polyketides versicolorones A-B (1–2), one new diketopiperazine derivative aspergiamide B methyl ester (3), along with twenty known compounds 4–23, were obtained from the EtOAc extract of the Cordyceps-colonizing fungus Aspergillus versicolor ZJUTE2. The structures of 1–3 were established by detailed interpretation of the spectroscopic data and their absolute configurations were established by comparative analyses of the calculated and experimental ECD spectra. In the in-vitro bioassay, compounds 8 and 21 exhibited significant inhibitory activity against the Escherichia coli β-glucuronidase (EcGUS) with IC50 values of 54.73 ± 2.69 and 56.59 ± 1.77 μM, respectively.

Wakodecaline C, new tetrahydrofuran-fused decalin metabolite isolated from fungus Pyrenochaetopsis sp. RK10-F058.

A new decalin-containing secondary metabolite, wakodecaline C, was isolated from a fungus Pyrenochaetopsis sp. RK10-F058 by screening structurally interesting metabolites based on LC/MS profiling. The structure including the absolute configuration was determined by a combination of spectroscopic methods including NMR and mass spectrometry, chemical reaction, and calculation of ECD spectra. Wakodecaline C has unique structural features containing a tetrahydrofuran-fused decalin skeleton and tetramic acid moiety, which are connected through a double bond. The compound showed moderate cytotoxicity against HL-60 cells and antimalarial activity against the Plasmodium falciparum 3D7 strain.

Cytotoxic steroids from the stems of Strophanthus divaricatus

Phytochemical investigation on the stems of Strophanthus divaricatus led to the isolation of four undescribed cardiac glycosides and one undescribed C21 pregnane, together with eleven known steroids. Their structures were elucidated by a comprehensive analysis of HRESIMS, 1D and 2D NMR spectra. The absolute configuration of 16 was determined by comparison of the experimental and computed ECD spectra. Compounds 1–13 and 15 displayed potent to significant cytotoxicity against human cancer cell lines K562, SGC-7901, A549 and HeLa with IC50 values of 0.02–16.08, 0.04–23.13, 0.06–22.31 and 0.06–15.13 μM, respectively.

Clavukoelloids A—M, Thirteen Rare N‐Containing Nardosinane Type Sesquiterpenoids from the Soft Coral Clavularia koellikeri

Comprehensive SummaryThirteen new nitrogen‐containing nardosinane‐type sesquiterpenoids, clavukoelloids A—M (1—13) with unique acrylamide fragments vs. the reported general nardosinane‐type sesquiterpenoids containing lactone, were isolated from the soft coral Clavularia koellikeri collected from the South China Sea. The structures and absolute configurations of new compounds were unambiguously determined by analysis of spectroscopic data, CP3, DP4+, ECD spectra, and X‐ray diffraction. Compound 6 showed anti‐inflammatory activities and hepatoprotective activities in transgenic fluorescent zebrafish.

Withanolides from Physalin angulata and their inhibitory effects on nitric oxide production.

Six new withanolides, angulasteroidins A-F (1-6), along with twelve known analogues (7-18) were isolated from the whole plants ofPhysalisangulata. Their structures were elucidated by analysis of 1D and 2D NMR, ECD spectra and HRESIMS data.Compounds 2-4, 7-9, and 15 exhibited significantly inhibitory activity on the production of nitric oxide in the LPS-activated RAW 264.7 mouse macrophage cell line with IC50values ranging from 0.23 to 9.06 μM.Six new withanolides, angulasteroidins A-F (1-6), along with twelve known analogues (7-18) were isolated from the whole plants of Physalis angulata . Their structures were elucidated by analysis of 1D and 2D NMR, ECD and IR spectra, HRESIMS data, and ECD calculation.Compounds 1 and 6 were rare 1-10 seco withanolides. Compounds 2-4, 7-9, and 15 exhibited significant inhibitory activity on the production of nitric oxide in the LPS-activated RAW 264.7 mouse macrophage cell line with IC50values ranging from 0.23 to 9.06 μM.

Diterpenoid quinones from the Salvia miltiorrhiza and their lung protective activity

Seven new diterpenoids quinones (1–6), together with five known ones (7–11), were isolated from the roots of Salvia miltiorrhiza Bunge. Their structures were elucidated by using 1D and 2D NMR data, while the relative and absolute configurations were confirmed by interpretations of the NOESY correlations and comparison of the experimental and calculated ECD spectra. In the evaluation of bioactivities, salviamilthiza C (3), significantly increased cell viability and decreased the expression of IL-1β in LPS-induced BEAS-2B cells.

Characterization of Serrulatane Diterpenoids in Eremophila phyllopoda subsp. phyllopoda by Triple High-Resolution α-Glucosidase/PTP1B/Radical Scavenging Profiling, NMR Spectroscopy, DFT-GIAO NMR, and Electronic Circular Dichroism Calculations.

Extracts of Eremophila phyllopoda subsp. phyllopoda showed α-glucosidase and PTP1B inhibitory activity with IC50 values of 19.6 and 13.6 μg/mL, respectively. High-resolution α-glucosidase/PTP1B/radical scavenging profiling was performed to establish a triple high-resolution inhibition profile that allowed direct pinpointing of the constituents responsible for one or more of the observed bioactivities. Subsequent targeted isolation and purification by analytical-scale HPLC led to the identification of 21 previously undescribed serrulatane diterpenoids, eremophyllanes A-U, as well as two known serrulatane diterpenoids, 1β-trihydroxyserrulatane (8) and 1α-trihydroxyserrulatane (10d), and five known furofuran lignans, (+)-piperitol (6), horsfieldin (7e), (-)-sesamin (9), (+)-sesamin (10h), and asarinin (10i). Their structures were elucidated by extensive analysis of HRMS and 1D and 2D NMR spectroscopic data. The relative configurations of the previously undescribed compounds were established by analysis of ROESY spectra as well as by DFT-GIAO NMR calculations followed by DP4+ probability analysis. The absolute configurations were determined by comparison of experimental and calculated ECD spectra. Serrulatane diterpenoids 7b and 14 exhibited α-glucosidase inhibitory activity with IC50 values of 28.4 and 64.2 μM, respectively, while 11, 12, 14, and 15 exhibited PTP1B inhibitory activity with IC50 values ranging from 16.6 to 104.6 μM. Hypothetical routes for formation of all identified serrulatane diterpenoids are proposed.

Stictamycin, an Aromatic Polyketide Antibiotic Isolated from a New Zealand Lichen-Sourced Streptomyces Species.

Here we describe the isolation and characterization of stictamycin, a new aromatic polyketide with activity against Staphylococcus aureus. Stictamycin was identified following metabolic profiling and bioactivity guided fractionation of organic extracts from Streptomyces sp. 438-3, an isolate from the New Zealand lichen Sticta felix. Comprehensive 1D and 2D NMR analyses were performed to determine the planar structure of stictamycin and relative configurations of stereo centers, with subsequent comparison of experimental and theoretical ECD spectra allowing elucidation of the absolute configuration. Whole-genome sequencing and biosynthetic gene cluster (BGC) analysis revealed that the Streptomyces sp. 438-3 strain contains an atypical type II polyketide (T2PKS) BGC capable of assembling polycyclic-aromatic ring skeletons. Cloning and knockout studies of this T2PKS BGC were used to confirm that it is responsible for the biosynthesis of stictamycin and elucidate a plausible biosynthetic scheme.

Enantioselective Nickel‐Catalyzed Hydrocyanation of Homostilbenes

AbstractWe investigated the previously unknown enantioselective Ni‐catalyzed hydrocyanation of 1,3‐diarylpropenes (homostilbenes). For this purpose, a series of (E)‐homostilbenes were prepared by (microwave‐assisted) Pd‐catalyzed coupling of allylic alcohols with aryl‐boronic acids. Employing our established catalyst system formed from Ni(cod)2 and a TADDOL‐derived chiral phosphine‐phosphite ligand and using TMSCN as an in situ source of HCN, the hydrocyanation of various homostilbenes was studied. The synthetic usefulness of the methodology was demonstrated in a short synthesis of the new (allo‐) colchicine analogue 7‐cyano‐11‐methoxy‐colchinol involving an PIDA‐mediated oxidative cyclization of the corresponding hydrocyanation product to set up the 7‐membered ring. The absolute configuration of 2,4‐diphenylbutyronitrile was assigned by comparison of experimental and calculated ECD spectra.

Tanzawaic Acid Derivatives from the Marine-Derived Penicillium steckii as Inhibitors of RANKL-Induced Osteoclastogenesis.

Seven new tanzawaic acid derivatives, steckwaic acids E-K (1-7), and one new benzene derivate (8), together with seven known tanzawaic acid analogues (9-16) were isolated from the marine algicolous fungus Penicillium steckii SCSIO 41040. The structures and absolute configurations of these new compounds (1-8) were determined by spectroscopic analyses, X-ray diffraction, and comparison of ECD spectra to calculations. Compounds 2, 10, and 15 inhibited lipopolysaccharide (LPS)-induced nuclear factor kappa-B (NF-κB) with IC50 values of 10.4, 18.6, and 15.2 μM, respectively. Compound 2 could suppress the receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation in bone marrow macrophage cells (BMMCs). To the best of our knowledge, this is the first report of osteoclastogenesis inhibitory activity for tanzawaic acid derivatives.

Alkaloids and Iridoids From the Aerial Parts of Rauvolfia cambodiana Pierre ex Pit. and Their Acetylcholinesterase Inhibitory Activity

Objective: Rauvolfia cambodiana has been used as a Vietnamese folk medicine to treat high blood pressure and for sedation and memory loss diseases. However, to date, there have been few studies on the chemical constituents and biological activity of this medicinal plant. This study aimed to find the chemical constituents of R cambodiana and evaluate their enhancement memory properties. Methods: The aerial parts of R cambodiana were powdered and ultrasonically extracted with methanol. The methanol extract was suspended in water and successively partitioned with dichloromethane and ethyl acetate to give dichloromethane, ethyl acetate, and water-soluble extracts. Each extract was fractionated and purified by column and HPLC chromatographic methods. The chemical structures of the isolated compounds were elucidated by analysis of HRESIMS, 1D and 2D NMR spectra, and experimental and TD-DFT calculated ECD spectra. The enhancement memory property of the compounds was evaluated by their in vitro acetylcholinesterase inhibitory activity. Results: Five alkaloids (1-5) and 2 iridoids (6 and 7), including one new one named rauvolcambonine (1), and 6 known compounds, perakine (2), ajmaline (3), 10-hydroxy-16- epi-affinine (4), sitsirikine (5), loganic acid (6), and secoxyloganin (7) were isolated and identified from the aerial parts of R cambodiana. Compounds 4 and 5 significantly showed acetylcholinesterase inhibitory effects in vitro with IC50 values of 30.1 ± 1.4 µM and 65.5 ± 3.3 µM, respectively. The other compounds inhibited acetylcholinesterase with IC50 values ranging from 111.0 ± 6.0 µM to 197.6 ± 19.8 µM. Conclusion: One new (1) and 3 other compounds (2, 4-7) were recorded from R cambodiana for the first time. The NMR spectroscopic data of compound 4 are reported herein for the first time. Our study preliminarily revealed that the vobasenal framework type alkaloids could be active ingredients of Rauvolfia species and responsibility for the enhancement memory property of these plants.

Targeted isolation of prenylated indole alkaloids from the marine-derived fungus Penicillium janthinellum HK1‑6 using molecular networking

Four prenylated indole alkaloids (1−4) were targeted isolated from the mangrove rhizosphere soil-derived fungus Penicillium janthinellum HK1-6 by using molecular networking strategies. Among them, the planar structure and relative configuration of notoamide X (1) were elucidated by detailed analysis of the spectroscopic data especially the NOESY spectrum for the first time and its absolute configuration was determined by ECD spectrum. Furthermore, curated molecular networks of MS/MS data were generated with GNPS which allowed highlighting six prenylated indole alkaloids (5, 6, 8, 9, 11, 12) that had not previously been identified in this fungus and two (7, 10) that had never been observed in any fungus. The MS/MS fragmentation pathway of these prenylated indole alkaloids was summarized.

Unreported cytochalasins from an acid-mediated transformation of cytochalasin J isolated from Diaporthe cf. ueckeri

Chemical investigation of an endophytic fungus herein identified as Diaporthe cf. ueckeri yielded four known compounds, named cytochalasins H and J and dicerandrols A and B. Reports of acid sensitivity within the cytochalasan family inspired an attempt of acid-mediated conversion of cytochalasins H and J, resulting in the acquisition of five polycyclic cytochalasins featuring 5/6/5/8-fused tetracyclic and 5/6/6/7/5-fused pentacyclic skeletons. Two of the obtained polycyclic cytochalasins constituted unprecedented analogues, for which the trivial names cytochalasins J4 and J5 were proposed, whereas the others were identified as the known phomopchalasin A, phomopchalasin D and 21-acetoxycytochalasin J3. The structures of the compounds were determined by extensive spectral analysis, namely HR-ESIMS, ESIMS and 1D/2D NMR. The stereochemistry of cytochalasins J4 and J5 was proposed using their ROESY data, biosynthetic and mechanistic considerations and by comparison of their ECD spectra with those of related congeners. All compounds except for cytochalasins H and J were tested for antimicrobial and cytotoxic activity. Cytochalasins J4 and J5 showed neither antimicrobial nor cytotoxic activity in the tested concentrations, with only weak antiproliferative activity observable against KB3.1 cells. The actin disruptive properties of all cytochalasins obtained in this study and of the previously reported cytochalasins RKS-1778 and phomopchalasin N were examined, and monitored by fluorescence microscopy using human osteo-sarcoma (U2-OS) cells. Compared to their precursor molecules (cytochalasins H and J), phomopchalasins A and D, 21-acetoxycytochalasin J3, cytochalasins J4 and J5 revealed a strongly reduced activity on the F-actin network, highlighting that the macrocyclic ring is crucial for bioactivity.

Indazole-derived synthetic cannabinoids: Absolute configuration determination and structure characterization by circular dichroism and DFT calculations

An increasing number of products containing synthetic cannabinoids pose a growing crisis to public health worldwide. Recently, a rising number of cases of serious adverse health effects, intoxications, and death cases associated with synthetic cannabinoids were reported. The current study represents the comprehensive structural analysis of three new synthetic cannabinoids (AB-, ADB- and AMB-FUBINACA) in solution investigated by electronic and vibrational circular dichroism together with the conventional methods of infrared and ultraviolet absorption spectroscopy, all supported by the density functional theory (DFT) calculations. The best level of theory to reproduce the experimental wavenumbers and wavelengths was found to be the B3PW91 method with a 6-311++G(d,p) basis set including the implicit solvent effect simulation. Very good agreement between the experimental and simulated spectra allowed us to determine the absolute configuration and a detailed interpretation of the IR absorption, VCD, ECD and UV spectra of AB-, ADB- and AMB-FUBINACA. In addition, the HOMO and LUMO electronic transitions were calculated.

Macrostines A and B: Tetracyclic fisicoccane from the fungus Periconia macrospinosa WTG-10

Two previous unreported fusicoccane diterpenoids macrostines A and B, together with seven known compounds were isolated from an extract of the fungus Periconia macrospinosa WTG-10. Their structures were elucidated by detailed analysis of spectroscopic data, NMR calculations with DP4+, and their absolute configurations were further determined by quantum chemical calculations of ECD spectra or X-crystallography. Macrostines A and B showed no cytotoxicity, antimicrobial activity and inhibitory effect on nitric oxide production in LPS-activated RAW264.7 macrophages. Compound 9 showed moderate activity against Bacillus subtilis.