Electronic Circular Dichroism Research Articles

Four New Polyprenylated Acylphloroglucinols from Hypericum perforatum L.

Hyperforatums A-D (1-4), four new polyprenylated acylphloroglucinols, together with 13 known compounds were isolated and identified from the aerial parts of Hypericum perforatum L. (St. John's wort). Their structures were confirmed with a comprehensive analysis comprising spectroscopic methods, including 1D and 2D NMR, HRESIMS, and electronic circular dichroism (ECD) calculations. Hyperforatum A featured an unusual chromene-1,4-dione bicyclic system, and hyperforatums B and C were two rare monocyclic PPAPs with five-membered furanone cores. Compound 1 exhibited a moderate inhibition effect on NO production in BV-2 microglial cells stimulated by LPS.

Induced Chirality in Canthaxanthin Aggregates Reveals Multiple Levels of Supramolecular Organization

AbstractCarotenoids tend to form supramolecular aggregates via non‐covalent interactions where the chirality of individual molecules is amplified to the macroscopic level. We show that this can also be achieved for non‐chiral carotenoid monomers interacting with polysaccharides. The chirality induction in canthaxanthin (CAX), caused by heparin (HP) and hyaluronic acid (HA), was monitored by chiroptical spectroscopy. Electronic circular dichroism (ECD) and Raman optical activity (ROA) spectra indicated the presence of multiple carotenoid formations, such as H‐ and J‐type aggregates. This is consistent with molecular dynamics (MD) and density functional theory (DFT) simulations of the supramolecular structures and their spectroscopic response.

Induced Chirality in Canthaxanthin Aggregates Reveals Multiple Levels of Supramolecular Organization.

Carotenoids tend to form supramolecular aggregates via non-covalent interactions where the chirality of individual molecules is amplified to the macroscopic level. We show that this can also be achieved for non-chiral carotenoid monomers interacting with polysaccharides. The chirality induction in canthaxanthin (CAX), caused by heparin (HP) and hyaluronic acid (HA), was monitored by chiroptical spectroscopy. Electronic circular dichroism (ECD) and Raman optical activity (ROA) spectra indicated the presence of multiple carotenoid formations, such as H- and J-type aggregates. This is consistent with molecular dynamics (MD) and density functional theory (DFT) simulations of the supramolecular structures and their spectroscopic response.

Ganonorsterone A, a norsteroid from the medicinal fungus Ganoderma lingzhi

Phytochemical investigation on the fruiting bodies of the medicinal fungus Ganoderma lingzhi led to the isolation of a new norsteroid, namely ganonorsterone A (1), together with one known steroid, cyathisterol (2). The structure and absolute configuration of compound 1 were assigned by extensive analysis of MS, NMR data, and quantum-chemical calculations including electronic circular dichroism (ECD) and calculated 13C NMR-DP4+ analysis. Bioassay results showed that compound 1 displayed moderate inhibition on NO production in RAW 264.7 macrophages.

Anti-Inflammatory Salicin Derivatives from the Barks of Salix tetrasperma.

The genus Salix L. is traditionally used in folk medicine to alleviate pain caused by various kinds of inflammation. In the present study, 10 undescribed salicin derivatives along with 5 known congeners were isolated from the barks of Salix tetrasperma, and their structures were elucidated by spectroscopic analyses, single-crystal X-ray diffraction, electronic circular dichroism (ECD) calculations, and chemical conversions. Compounds 4-6 significantly inhibited NO production in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages, and the most active 4 obviously suppressed the production of IL-1β and IL-6 and decreased iNOS and COX-2 expression in a dose-dependent manner. Further Western blotting analysis revealed that the anti-inflammatory mechanism of 4 is possibly mediated through the MAPK and NF-κB signaling pathways.

Boswellianols A-I, Structurally Diverse Diterpenoids from the Oleo-Gum Resin of Boswellia carterii and Their TGF-β Inhibition Activity.

Olibanum, a golden oleo-gum resin from species in the Boswellia genus (Burseraceae family), is a famous traditional herbal medicine widely used around the world. Previous phytochemical studies mainly focused on the non-polar fractions of olibanum. In this study, nine novel diterpenoids, boswellianols A-I (1-9), and three known compounds were isolated from the polar methanolic fraction of the oleo-gum resin of Boswellia carterii. Their structures were determined through comprehensive spectroscopic analysis as well as experimental and calculated electronic circular dichroism (ECD) data comparison. Compound 1 is a novel diterpenoid possessing an undescribed prenylmaaliane-type skeleton with a 6/6/3 tricyclic system. Compounds 2-4 were unusual prenylaromadendrane-type diterpenoids, and compounds 5-9 were new highly oxidized cembrane-type diterpenoids. Compounds 1 and 5 showed significant transforming growth factor β (TGF-β) inhibitory activity via inhibiting the TGF-β-induced phosphorylation of Smad3 and the expression of fibronectin and N-cadherin (the biomarker of the epithelial-mesenchymal transition) in a dose-dependent manner in LX-2 human hepatic stellate cells, indicating that compounds 1 and 5 should be potential anti-fibrosis agents. These findings give a new insight into the chemical constituents of the polar fraction of olibanum and their inhibitory activities on the TGF-β/Smad signaling pathway.

Bioassay-Guided Isolation and Identification of Cytotoxic Compounds from Melaleuca quinquenervia Fruits.

The fruit extract of Melaleuca quinquenervia yielded a total of 19 compounds, including two novel spiro-biflavonoid enantiomers (1a and 1b) and a chalcone derivative (3). Their structures were determined through spectroscopic analysis. The enantiomers of the racemic mixture of compound 1 were successfully resolved into (+)-1 and (-)-1 using chiral-phase HPLC. Single-crystal X-ray diffraction analysis was also used to confirm the structure of 1. The enantiomeric configurations of 1 and 2 were determined through a comparison of the calculated and experimental electronic circular dichroism spectra. Compounds 2 (melanervin), 14 (methyl betulinate), 15 (3-O-acetylbetulinic acid), and 16 (pyracrenic acid) were found to be highly cytotoxic, with compound 16 showing superior growth inhibition of nonsmall cell lung cancer cells (A549 cells) (IC50 2.8 ± 0.1 μM) compared to cisplatin (IC50 3.3 ± 0.0 μM), a positive control chemotherapeutic drug. Both compound 16 and cisplatin were significantly more cytotoxic toward A549 lung cancer cells compared to nontumorigenic Vero E6 cells.

Sesquiterpenoids from the roots of Lindera glauca and their cytotoxicity activities.

The chemical investigation of the roots of Lindera glauca guided the isolation and identification of 3 new sesquiterpenoids, namely glaucatotones J-L (1-3), and one known congener, (1β,5β)-1-hydroxyguaia-4(15),11(13)-dieno-12,5-lactone (4). The structures of new compounds were established based on comprehensive spectrographic methods, mainly including 1D & 2D NMR and HRESIMS analyses, and the absolute configurations were further confirmed by the comparison of experimental and calculated electronic circular dichroism. The cytotoxicity activities of isolates were evaluated, and the results showed that they have moderate cytotoxic activities.

Three new constituents from the stems of Knema globularia and their α-glucosidase inhibitory activity

Three new metabolites (1−3) were isolated from the stems of Knema globularia, along with five known compounds, including kaempferol (4), quercetin (5), isovanillic acid (6), protocatechuic acid (7), and gallic acid (8). Their structures were deduced using NMR spectroscopic, mass spectrometric analyses, and literature data. The absolute configurations of 1−3 were established by electronic circular dichroism (ECD) spectroscopy. α-Glucosidase inhibitory activities of those compounds were evaluated using a spectrophotometric method, compounds 1−3 showed very strong effects towards α-glucosidase with IC50 values 1.59, 0.58 and 1.37 µM, respectively (the positive control, acarbose, IC50 93.63 µM). Simultaneously, enzyme kinetics study indicated that 2 was a mix-type inhibitor. 2 interacted well in the active site of α-glucosidase enzyme, primarily through hydrogen bonds and hydrophobic interactions.

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.

Isolation and biomimetic synthesis of phenylpropionyl phenylethylamines from Chloranthus henryi

In this study, ten phenylpropionyl phenylethylamines, including five previously undescribed ones (1a/b, 2a/b, and 3), five known analogues (4–8), and two established phenylpropanoids precursors (9, 10) were isolated from the aerial parts of Chloranthus henryi Hemsl. Their structures, including absolute configurations, were determined by high-resolution mass spectrometry, enantio-separation, electronic circular dichroism calculation, and single crystal diffraction. Compounds 1a and 1b were the first examples of natural hetero-[2 + 2] cycloaddition products between phenylpropionyl phenylethylamine and phenylpropene. The plausible hetero-[2 + 2] biosynthesis pathway was confirmed by a photocatalytic biomimetic synthesis in eight steps, which also led to the production of three other potential natural homo-[2 + 2] adducts (1′a/b, 2′, and 3′). Bioactivity screening indicated that these adducts bear medium inhibitory activity on nitric oxide generation, with IC50 values of 6–35 μM in RAW 264.7 macrophages.

Limonoids from the fruits of Chisocheton erythrocarpus and their mosquito larvicidal activities

Phytochemical study of the fruits of Chisocheton erythrocarpus (Hiern) allowed the identification of eight undescribed limonoids, namely erythrocarpines O – V (1–6, 7a and 7b), along with seven known compounds. The structures of these compounds were elucidated based on spectroscopic and HRMS data, along with electronic circular dichroism to configure the absolute configuration. Erythrocarpines O and P are γ-hydroxybutenolide analogs of mexicanolide-type limonoids while erythrocarpine Q – V are phragmalin-type limonoids possessing a 1,29-oxymethylene bridge with either benzoyl or cinnamoyl moiety in their structures. Mosquito larvicidal activity revealed that crude DCM extract of C. erythrocarpus possessed a good larvicidal effect against Aedes aegypti larvae in 48 h (LC50 = 153.0 ppm). Subsequent larvicidal activity of isolated compounds indicated that erythrocarpine G (10) and 14-deoxyxyloccensin K (11) were responsible for the enhanced larvicidal effect of the extract, reporting LC50 values of 18.55 ppm and 41.16 ppm, respectively. Moreover, residual activity testing of the crude DCM extract revealed that the duration of its larvicidal effects is up to 14 days, where it maintained a 98 % larval mortality throughout the test period, under laboratory conditions.

Unrevealing the Nitrogen Elusive Chirality of 3-Sulfanyl and 3-Sulfinyl N-Tosyl Isoindolinones by ECD Spectra: An Experimental and Theoretical Investigation.

The nitrogen-hybridization/pyramidalization of two solvated N-tosylisoindolinone derivatives having chiral residues in adjacent (I) or adjacent and distal (II) position has been investigated by a theoretical-computational procedure based on Molecular Dynamics simulations and Quantum-Chemical calculations. After validation of our methodology in providing a reliable repertory of conformations by modeling the electronic circular dichroism (EDC) spectra, the electronic features associated with N-pyramidalization were further characterized through Natural Bond Order (NBO) analysis. Comparing against the N-geometry observed in crystal structures as a reference, our findings reveal that the presence of neighbouring chiral centers induces a more pronounced N-pyramidalization in solution than in the solid state, both in I and II. Furthermore, NBO analysis confirms that the N-lactam mostly retains the sp2 character but exhibits slight configurational distortion (ξI=13°; ξII=21°), which significantly influences the chiroptical activities observed in ECD spectra of I and II. This substantiates the N-lactams as configurationally stable chiral centers.

Chaetoxylariones A–G: undescribed chromone-derived polyketides from co-culture of Chaetomium virescens and Xylaria grammica enabled via the molecular networking strategy

By co-culturing two endophytic fungi (Chaetomium virescens and Xylaria grammica) collected from the medicinal and edible plant Smilax glabra Roxb. and analyzing them with MolNetEnhancer module on GNPS platform, seven undescribed chromone-derived polyketides (chaetoxylariones A–G), including three pairs of enantiomer ones (2a/2b, 4a/4b and 6a/6b) and four optical pure ones (1, 3, 5 and 7), as well as five known structural analogues (8–12), were obtained. The structures of these new compounds were characterized by NMR spectroscopy, single-crystal X-ray diffraction, 13C NMR calculation and DP4+ probability analyses, as well as the comparison of the experimental electronic circular dichroism (ECD) data. Structurally, compound 1 featured an unprecedented chromone-derived sulfonamide tailored by two isoleucine-derived δ-hydroxy-3-methylpentenoic acids via the acylamide and NO bonds, respectively; compound 2 represented the first example of enantiomeric chromone derivative bearing a unique spiro-[3.3]alkane ring system; compound 3 featured a decane alkyl side chain that formed an undescribed five-membered lactone ring between C-7′ and C-10′; compound 4 contained an unexpected highly oxidized five-membered carbocyclic system featuring rare adjacent keto groups; compound 7 featured a rare methylsulfonyl moiety. In addition, compound 10 showed a significant inhibition towards SW620/AD300 cells with an IC50 value of PTX significantly decreased from 4.09 μM to 120 nM, and a further study uncovered that compound 10 could obviously reverse the MDR of SW620/AD300 cells.

A derivative of trihydroxynaphthalenone and a pyrone metabolite from the endophytic fungus Talaromyces purpurpgenus

A newly discovered trihydroxynaphthalenone derivative, epoxynaphthalenone (1) involving the condensation of ortho-hydroxyl groups into an epoxy structure, and a novel pyrone metabolite characterized as pyroneaceacid (2), were extracted from Talaromyces purpurpgenus, an endophytic fungus residing in Rhododendron molle. The structures of these compounds were elucidated through a comprehensive analysis of their NMR and HRESIMS data. The determination of absolute configurations was accomplished using electronic circular dichroism (ECD) calculations and CD spectra. Notably, these recently identified metabolites exhibited a moderate inhibitory activity against xanthine oxidase (XOD).

Ergosterols with rare peroxide, oxetane ring moiety, and a lactone ring from Aspergillus spectabilis and their immunosuppressive activities

Ten ergostane-type steroids, including seven undescribed ones named spectasteroids A–G, were obtained from Aspergillus spectabilis. Their structures and absolute configurations were determined based on HRESIMS, NMR, ECD calculations, and single-crystal X-ray diffraction analyses. Structurally, spectasteroid A was a unique example of aromatic ergostane-type steroid that featured a rare peroxide ring moiety; spectasteroid B contained a rare oxetane ring system formed between C-9 and C-14; and spectasteroid C was an unusual 3,4-seco-ergostane steroid with an extra lactone ring between C-3 and C-9. Spectasteroids F and G specifically showed inhibitory effects against concanavalin A-induced T lymphocyte proliferation and lipopolysaccharide-induced B lymphocyte proliferation, with IC50 values ranging from 2.33 to 4.22 μM. Spectasteroid F also showed excellent antimultidrug resistance activity, which remarkable enhanced the inhibitory activity of PTX on the colony formation of SW620/Ad300 cells.

Chaeglobol A, an unusual octocyclic sterol with antifungal activity from the marine-derived fungus Chaetomium globosum HBU-45

Chemical investigation of the marine-derived fungus Chaetomium globosum HBU-45 led to the discovery of chaeglobol A (1). Its structure was determined by spectroscopic analysis, computational electronic circular dichroism (ECD)/optical rotatory dispersion (ORD) methods, and X-ray crystallography. Compound 1 represents a new skeleton with an uncommon 6/6/6/5/6/5/6/5 octacyclic system, which is presumably biosynthesized via a [4+2] cycloaddition and an enzymatic cyclization. Chaeglobol A (1) exhibited inhibitory activity against B. dothidea by destroying cell membrane integrity and causing oxidative damage within the cells.

New pimarane diterpenoids with antibacterial activity from fungus Arthrinium sp. ZS03

A comprehensive chemical study of the endophytic fungus Arthrinium sp. ZS03, associated with Acorus tatarinowii Schott, yielded eleven pimarane diterpenoids (compounds 1-11), including seven novel compounds designated arthrinoids A-G (1-7). The determination of their structures and absolute configurations was achieved through extensive spectroscopic techniques, quantum chemical calculations of electronic circular dichroism (ECD), and single-crystal X-ray diffraction analysis. Furthermore, 7 demonstrated inhibitory activity against Klebsiella pneumoniae, comparable to the reference antibiotic amikacin, with a minimum inhibitory concentration (MIC) of 8 μg·mL-1.

Synthesis, Resolution, and Absolute Configuration of a Phosphine-Based Hemicryptophane Cage with an Endo Phosphorus Lone Pair and Formation of the Corresponding Gold Complex.

The synthesis, characterization, and chiroptical properties of a new class of hemicryptophanes combining a phosphine moiety and a cyclotriveratrylene unit are reported. The synthesis was short and efficient. The racemic mixture of the cage was resolved by chiral high-performance liquid chromatography (HPLC), giving access to enantiopure molecular cages, whose absolute configurations could be assigned by electronic circular dichroism (ECD) spectroscopy. These new phosphines were then reacted with gold in order to make the corresponding enantiopure gold complexes. The X-ray structure reveals an endohedral functionalization of the cage with the gold metal entrapped in the heart of the cavity, leading to a Vbur of 58%. Moreover, the chirality of the cyclotriveratrylene unit was found to control the chiral arrangement of the aryl group linked to the phosphorus atom, located at the opposite side of the cavity.

Rakicidin J and K, two cytotoxic and antibacterial cyclic depsipeptides from the marine bacterium Micromonospora chalcea

Rakicidin J (1) and rakicidin K (2), two new cyclic depsipeptides, were isolated from culture broth of Micromonospora chalcea FIM-R150103. Their structures were elucidated by extensive analysis of NMR, HR-ESI-MS, and electronic circular dichroism (ECD) data. The two compounds showed strong cytotoxic activity against human colon carcinoma HCT-8 and human pancreatic cancer PANC-1 cells under normoxic and hypoxic conditions in the range of IC50 values from 0.024 to 0.79 μg/mL. Moreover, compounds 1 and 2 also showed moderate antibacterial activity against ten Gram-positive bacterial strains with MIC values ranging from 4 to more than 32 μg/mL. Structure–activity relationship of these two compounds with a close analogue, rakicidin B1, is also discussed.