Quantum Chemical CD Calculations Research Articles

Sulfur-containing spiroketals from Breynia disticha and evaluations of their anti-inflammatory effect.

Breynia spp. are a key source of sulfur-containing spiroketal glycosides with potential anti-inflammatory activity. In this study, three new sulfur-containing spiroketals - breynin J (1), epibreynin J (2), and probreynogenin (3) - along with four known compounds - probreynin I (4), phyllaemblic acid (5), breynin B (6), and epibreynin B (7) - were isolated from the roots of Breynia disticha. The structures of compounds 1-7 were elucidated by extensive 1D and 2D NMR spectroscopic analyses, including 1D total correlation spectroscopy (TOCSY), HSQC, HMBC, double quantum-filtered (DQF)-COSY, heteronuclear two-bond correlation (H2BC), and HSQC-TOCSY experiments, as well as high-resolution electrospray ionization HRESIMS analysis, and quantum chemical electronic CD calculations. Furthermore, the absolute configurations of sugar residues were determined by derivatization of the hydrolysates with ʟ-cysteine methyl ester and o-tolyl isothiocyanate followed by HPLC analysis. The anti-inflammatory effects of the isolated compounds were evaluated based on the mRNA levels of proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophage cells. Compounds 1, 2, 6, and 7 inhibited the increase in interleukin (IL)-1β and IL-6 mRNA levels stimulated by LPS. Moreover, the most potent compound 7 was found to significantly inhibit the production of IL-1β and IL-6 proteins, as revealed by the analysis of culture supernatants.

Two new neolignans and an indole alkaloid from the stems of Nauclea officinalis and their biological activities

A pair of new diastereoisomers neolignans (1–2) and a new alkaloid (7) were isolated from the stems of Nauclea officinalis: naucleaoxyneolignoside A (1), naucleaoxyneolignoside B (2), (2S,3S)-javaniside (7), together with nine known compounds, 2S-3,3-di-(4-hydroxy-3-methoxyphenyl)-propane-1,2-diol (3), threo-1,2-bis-(4-hydroxy-3-methoxyphenyl)-propane-1,3-diol (4), nauclefine (5), angustidine (6), naucleoxoside A (8), naucleoxoside B (9), angustoline (10), (3S,19S)-3,14-dihydroangustoline (11), and (3S,19R)-3,14-dihydroangustoline (12).The structures of 1, 2 and 7 were elucidated by extensive spectroscopic methods and the known compounds were identified by comparison of their data with those reported in the literature. The absolution configurations of 1, 2, 7,11 and 12 were confirmed by the quantum chemical CD calculation method. Compounds 1–9 showed weak to moderate inhibitory activity on nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro with IC50 values comparable to that of dexamethasone. In addition, compounds 1–9 were evaluated for the antibacterial and cytotoxic effects, and the results revealed that these compounds showed no anti-bacterial activity, and compounds 3–6 showed modest cytotoxic activity.

Nor-guanacastepene pigments from the Chilean mushroom Cortinarius pyromyxa

For the first time, the pigment composition of basidiocarps from the Chilean mushroom Cortinarius pyromyxa was studied under various aspects like phylogeny, chemistry and antibiotic activity. A molecular biological study supports the monotypic position of C. pyromyxa in subgenus Myxacium, genus Cortinarius. Four undescribed diterpenoids, named pyromyxones A-D, were isolated from fruiting bodies of C. pyromyxa. Their chemical structures were elucidated based on comprehensive one- and two-dimensional NMR spectroscopic analysis, ESI-HRMS measurements, as well as X-ray crystallography. In addition, the absolute configurations of pyromyxones A-D were established with the aid of JH,H, NOESY spectra and quantum chemical CD calculation. The pyromyxones A-D possess the undescribed nor-guanacastane skeleton. Tested pyromyxones A, B, and D exhibit only weak activity against gram-positive Bacillus subtilis and gram-negative Aliivibrio fischeri as well as the phytopathogenic fungi Botrytis cinerea, Septoria tritici and Phytophthora infestans.

Cablinosides A and B, Two Glycosidic Phenylacetic Acid Derivatives from the Leaves of Pogostemon cablin.

A pair of new glycosidic epimers, cablinosides A (1a) and B (1b) were isolated from the leaves of Pogostemon cablin. The structures with absolute configurations of 1a and 1b were elucidated by extensive NMR investigation, and quantum chemical CD calculations. The epimer mixture 1 showed moderate α-glucosidase inhibitory activity and no significant cytotoxic activity against HepG2 cells.

Brachyanins A-C, pinene-derived meroterpenoids and phloroglucinol derivative from Leptospermum brachyandrum

A pair of epimer brachyanins A (1) and B (2), along with a new phloroglucinol brachyanin C (3), were isolated from the leaves of Leptospermum brachyandrum. Brachyanins A (1) and B (2) were the first example of novel meroterpenoid with a unique skeleton that combined a synacrpic acid and a pinene units via a benzyl moiety. Their structures were elucidated through the application of extensive spectroscopic measurements and single-crystal X-ray diffraction analysis and with the absolute configurations of 1 and 2 were confirmed by the quantum chemical CD calculation. The hetero Diels-Alder as the key biotransformation was proposed to account for the biosynthesis of brachyanins A and B sheding light by the potential procursor brachyanin C.

Four new norlignan glycoside isomers from the twigs of Cephalotaxus oliveri Mast.

Four novel isomers of norlignan glycoside were isolated from Cephalotaxus oliveri Mast.. Their structures were elucidated as 3S-4″-O-β-d-glucopyranosylnyasol 1, 3S-4′-O-β-d-glucopyranosylnyasol 2, 3S-4″-O-β-d-glucopyranosylhinokiresinol 3, 3S-4′-O-β-d-glucopyranosylhinokiresinol 4 by extensive spectroscopic methods including 1D and 2D NMR experiments (1H, 13C, DEPT, 1H–1H COSY, HSQC, HMBC, ROESY) along with HR-ESIMS and comparison to literature data. Their absolute configurations were elucidated through CD spectra coupled with the quantum chemical CD calculations.

Lanostane triterpenoids from fruiting bodies of basidiomycete Stereum sp., structures and biological activities.

Twelve new lanostane triterpenoids, sterenoids A-L (1-12) have been isolated from fruiting bodies of the basidiomycete Stereum sp. Compounds 1-12 are rare 14(13→︀12)abeo-lanostane triterpenoids featuring remarkable 13R configurations that discriminate from the previously covered counterparts. Their structures and absolute configurations are assigned on the basis of in-depth one- and two-dimensional NMR spectroscopic analysis, as well as unbiased quantum chemical NMR and electronic CD calculations. All isolates are evaluated for their in vitro cytotoxicity against five human tumor cell lines. Compound 5 exhibits potent cytotoxic activities against tumor cell lines HL-60 and SMMC-7721 with IC50 values of 4.7 and 7.6 μM, respectively.

Structural and stereochemical elucidation of new hygrophorones from Hygrophorus abieticola (Basidiomycetes)

Four new hygrophorones (1–4) together with the known hygrophorone B12 (5) have been isolated from fruiting bodies of the basidiomycete Hygrophorus abieticola Krieglst. ex Gröger & Bresinsky. Their structures were assigned on the basis of extensive one and two dimensional NMR spectroscopic analyses as well as ESI-HRMS measurements. Among these compounds, two previously undescribed hygrophorone types, named hygrophorone H12 (3) and 2,3-dihydrohygrophorone H12 (4), were identified. The absolute configuration of hygrophorone E12 (2) is suggested based on quantum chemical CD calculations, while a semisynthetic approach in conjunction with computational studies and analysis of NOE interactions allowed the stereochemical assignment of compounds 3 and 4. Additionally, semisynthetic derivatives of hygrophorone B12 (5) were generated by acetylation of the hydroxyl groups. The biological activity of the natural and semisynthetic hygrophorones was evaluated against phytopathogenic organisms, revealing that the α,β-unsaturated carbonyl functionality is likely to be an essential structural feature. Hygrophorone B12 (5) was identified as the most active compound, acting against both ascomycetous fungi and oomycetes.

Structure and Absolute Configuration of Pseudohygrophorones A(12) and B(12), Alkyl Cyclohexenone Derivatives from Hygrophorus abieticola (Basidiomycetes).

Pseudohygrophorones A(12) (1) and B(12) (2), the first naturally occurring alkyl cyclohexenones from a fungal source, and the recently reported hygrophorone B(12) (3) have been isolated from fruiting bodies of the basidiomycete Hygrophorus abieticola Krieglst. ex Gröger & Bresinsky. Their structures were assigned on the basis of extensive one- and two-dimensional NMR spectroscopic analysis as well as ESI-HRMS measurements. The absolute configuration of the three stereogenic centers in the diastereomeric compounds 1 and 2 was established with the aid of (3)JH,H and (4)JH,H coupling constants, NOE interactions, and conformational analysis in conjunction with quantum chemical CD calculations. It was concluded that pseudohygrophorone A(12) (1) is 4S,5S,6S configured, while pseudohygrophorone B(12) (2) was identified as the C-6 epimer of 1, corresponding to the absolute configuration 4S,5S,6R. In addition, the mass spectrometric fragmentation behavior of 1-3 obtained by the higher energy collisional dissociation method allows a clear distinction between the pseudohygrophorones (1 and 2) and hygrophorone B(12) (3). The isolated compounds 1-3 exhibited pronounced activity against phytopathogenic organisms.

Two New Oxindole Alkaloid Glycosides from the Leaves of Nauclea officinalis

Two new oxindole alkaloid glycosides, nauclealomide A and (3S,7R)-javaniside, were isolated from the leaves of Nauclea officinalis. Their structures and absolute configurations were elucidated by means of NMR, HRESIMS, X-ray diffraction, acid hydrolysis and quantum chemical CD calculation. Nauclealomide A is a novel monoterpenoid oxindole alkaloid possessing a rare tetrahydro-2H-1,3-oxazine ring.

Five New Acylphloroglucinol Glycosides from the Leaves of Eucalyptus robusta

Five new acylphloroglucinol glycosides, robustasides A-E (1-5), together with a known one (6), were isolated from the leaves of Eucalyptus robusta. The structures were elucidated on the basis of extensive spectroscopic and spectrometric analysis and chemical evidence. The absolute configuration of 1 was further determined by quantum chemical CD calculation.

New bhimamycins from Streptomyces sp. AK 671

From the wild-type strain Steptomyces sp. AK 671, three nitrogen-containing octaketides were isolated, bhimamycins F, H and I, besides the known azaanthraquinone utahmycin A and polyketide shunt products SEK 4, SEK 4b, mutactin, dehydromutactin and EM18. The structures were characterized by MS and NMR experiments. The hitherto unknown absolute configuration of the two enantiomers of EM18 was determined by online-CD spectroscopy and quantum-chemical CD calculations. Bhimamycins H and I show weak antibacterial activities, whereas the enzyme phosphodiesterase 4 is strongly inhibited by bhimamycins H and I, which has never been reported for nitrogen-containing octaketides. In addition, bhimamycin H inhibits the enzyme glycogen synthase kinase-3β.

Cis‐Clerodane Diterpenes from the Liverwort Scapania ciliata

Chemical investigation of the Chinese liverwort Scapania ciliata led to the isolation of four new cis-clerodane lactones, named ciliatolides A-D (1-4, resp.), among which compound 1 was found to be a tetranorclerodanoid. Their structures were determined by extensive analysis of spectroscopic data, and, in the case of compound 1, together with a single-crystal X-ray diffraction analysis. The absolute configurations were established by analysis of the CD spectra and by quantum-chemical CD calculations. The cytotoxicities of compounds 1-4 were preliminarily tested against the PC3 and MCF-7 cell lines.

Oleonin, the first secoiridoid with 1α-configuration from Ligustrum lucidum

The first secoiridoid with unusual 1α-configuration, oleonin (1), was isolated from the fruits of Ligustrum lucidum. The chemical structure and absolute stereochemistry were elucidated on the basis of exhaustive NMR spectral analyses, single crystal X-ray diffraction and quantum chemical CD calculation. The plausible biogenetic pathway of 1 and the evaluation of this mechanism are also described.

A new cadinane sesquiterpene from the rhizomes of Alpinia officinarum

AimTo investigate the chemical constituents of the rhizomes of Alpinia officinarum. MethodsCompounds were isolated by various column chromatographic methods, and their structures were identified based on their physicochemical properties and spectral data. ResultsA cadinane sesquiterpene, alpiniaterpene A (1), was isolated. Its structure with absolute configuration was established by means of HR-ESI, NMR, and quantum chemical CD calculation. ConclusionCompound 1 is a new compound.

Antibacterial Spirobisnaphthalenes from the North American Cup Fungus Urnula craterium

Urnucratins A-C (1-3), which possess an unusual bisnaphthospiroether skeleton with one oxygen bridge and one C-C bridge and represent a new subclass of bisnaphthalenes, were isolated from the North American cup fungus Urnula craterium. Their structures, including absolute configurations, were determined by means of HRMS, NMR, and quantum chemical CD calculations. Urnucratin A (1) was found to be active against methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and Streptococcus pyogenes with MIC values of 2, 1, and 0.5 μg/mL, respectively.

A novel antifouling alkaloid from halotolerant fungus Penicillium sp. OUCMDZ-776

Penispirolloid A (1), a novel alkaloid possessing a unique spiro imidazolidinyl skeleton, was isolated from a halotolerant fungal strain, Penicillium sp. OUCMDZ-776. Its structure was elucidated on the basis of spectroscopic methods and quantum chemical CD calculation. Compound 1 showed significant antifouling activity toward Bugula neritina larvae with EC50 of 2.40μg/ml. Plausible biogenesis of compound 1 was also proposed.

Determination of atropisomeric configurations of macrocyclic bisbibenzyls by HPLC-CD/UV and quantum chemical calculations

Isoriccardin C (1) and riccardin D (2), isolated from the liverwort Reboulia hemisphaerica, were first characterized to be a mixture of two enantiomeric atropisomers by online chiral high-performance liquid chromatography-circular dichroism (HPLC-CD) analysis. Exemplarily for bisbibenzyls of the diarylether-biphenyl type, the absolute atropisomeric configurations of compunds 1 and 2 were determined by the analysis of their CD data coupled with quantum chemical CD calculations.

Chloropupukeanolides C–E: Cytotoxic Pupukeanane Chlorides with a Spiroketal Skeleton from Pestalotiopsis fici

Chloropupukeanolides C-E (8-10), three highly functionalized secondary metabolites featuring a novel spiroketal skeleton derived from the chlorinated tricyclo-[4.3.1.0(3, 7)]-decane (pupukeanane) and the 2,6-dihydroxy-4-methylbenzoic acid moieties, were isolated from the scale-up fermentation extract of the plant endophytic fungus Pestalotiopsis fici. The constitutions of compounds 8-10 were elucidated primarily by NMR experiments. Their relative configurations were deduced by analogy to metabolites 4-6, which were previously isolated from the same fungus. The absolute configuration of 8 was assigned by X-ray crystallography and those of 9 and 10 by quantum-chemical CD calculations. Biogenetically, chloropupukeanolides C-E (8-10) are presumably derived from the same oxidation-induced Diels-Alder reaction pathway as compounds 1 and 4-7, via the putative biosynthetic precursors 2 and 3. The opposite configurations of the complete "Southern parts" of 8 and 9 suggests that this Diels-Alder reaction is stereochemically not very selective. Compounds 8-10 showed significant cytotoxicity against a small panel of human tumor cell lines and weak activities against the pathogens of tropical diseases.

Aspergiolides C and D: Spirocyclic Aromatic Polyketides with Potent Protein Kinase c‐Met Inhibitory Effects

Variation of the cultivation conditions for Aspergillus glaucus led to the discovery of two novel spirocyclic aromatic polyketides, aspergiolides C (3) and D (4). Their constitutions were elucidated by a combination of spectroscopic methods and isotope-labeling experiments. Aspergiolides C (3) and D (4) occur as racemic mixtures, the resolution of which was succeeded by HPLC on a chiral phase. The absolute configurations of their enantiomers were assigned online, from the peaks in the chromatogram, by a combination of HPLC-CD and quantum chemical CD calculations. Both compounds were found to inhibit the kinase activities of the receptor tyrosine kinases (RTKs) c-Met, Ron, and c-Src with low-micromolar IC(50)s. The enantiomers of 3 were resolved by HPLC on a chiral phase. Both enantiomers showed a comparable inhibition of the HGF-induced autophosphorylation of c-Met and of subsequent cell migration.