Chemical constituents of Ligularia virgaurea and its diversity in southwestern Sichuan of China

Chemical constituents of root extract and the nucleotide sequences of the atpB-rbcL intergenic region and the internal transcribed spacers (ITSs) of the ribosomal RNA gene were studied for Ligularia virgaurea var. virgaurea collected in southwestern Sichuan Province of China. Eleven samples were collected. Four of them were found to contain four new furanoeremophilanes, virgaurenones A-D, as well as a new eremophilanolide, virgaurenolide A. The other samples contained different furanoeremophilanes and their derivatives including nor-type of compounds, two of which were new. Diversity was found to be present in the nucleotide sequences as well. The chemical composition was found to be correlated with the ITS variation but not with the geographic distribution of the samples.     

Sesquiterpenoids and Lignans from Ligularia virgaurea spp. oligocephala

From the BuOH extract of the whole plant of Ligularia virgaurea spp. oligocephala, a series of sesquiterpenes, sesquiterpene glycosides, and lignan glycosides were isolated, including the three new compounds (1α)‐1‐hydroxy‐8‐oxo‐eremophila‐6,9‐dien‐12‐oic acid ( 1 ), 8‐[(β‐D ‐glucopyranosyl)oxy]eremophila‐1(10),8,11‐trien‐2‐one ( 2 ), and 4‐[(β‐D ‐glucopyranosyl)oxy]pinoresinol ( 4 ). Their structures were elucidated by 1D‐ and 2D‐NMR as well as HR‐ESI‐MS analyses, and by comparison of the spectroscopic data with those reported for structurally related compounds.     

Chemical and genetic diversity of Ligularia virgaurea collected in northern Sichuan and adjacent areas of China. Isolation of 13 new compounds

Root chemicals and DNA sequences were analyzed for Ligularia virgaurea collected in the northern Sichuan Province and adjacent areas of China. Thirty-eight samples were found to contain five chemotypes, two known and three new ones. From samples of the new chemotypes, 13 new compounds were isolated, including 3 sesquiterpene dimers and some rearranged eremophilanes. The DNA sequences suggested that the chemotype differentiation had a genetic origin.     

Structure and cytotoxic evaluation of five 12-oxygenated eremophilanes from Ligularia lingiana

Five new 12-oxygenated eremophilane sesquiterpenoids bearing a B-ring enone system were isolated from Ligularia lingiana S.W. Liu (Asteraceae) collected in China. Compound 5 was a Diels–Alder adduct of 3α-angeloyloxy-7βH-8-oxoeremophila-9,11(13)-dien-12-al and the monoterpene, ocimene. Compound 1 showed cytotoxic activities against HeLa, HL60, Jurkat, and NIH-3T3 cells at IC₅₀ 0.0407, 0.440, 0.313, and 3.48 μM, respectively.     

Overlapping chemical and genetic diversity in Ligularia lamarum and Ligularia subspicata. Isolation of ten new eremophilanes and a new seco-bakkane compound

Root chemicals and DNA sequences were analyzed for Ligularialamarum samples collected in Yunnan and Sichuan Provinces of China and the relationship between the plant and Ligulariasubspicata, its taxonomically closest species, was examined. Both species produce furanoeremophilanes and eremophilan-8-one derivatives as the major components. Eleven new compounds, including a new seco-bakkane compound, were isolated. The two species were found to harbor overlapping intra-specific diversities with respect to the chemicals and the DNA sequences.     

Five new eremophilane derivatives from Ligularia sagitta

Ligulasagitins A-E (1-5), five new eremophilane-derived metabolites possibly formed via a Diels-Alder reaction in the biosynthetic process, were isolated from Ligularia sagitta Maxim. Among them 1 and 2 possess a novel C19 skeleton, 4 and 5 are two novel dimeric eremophilane type derivatives. Their structures were determined by extensive spectroscopic analysis and the structure of 2 was also confirmed by a single-crystal X-ray diffraction analysis. Furthermore, 4 and 5 showed weak cytotoxic activity against HL-60 (human promyelocytic leukemia) cells.     

Bieremoligularolide and eremoligularin, two novel sesquiterpenoids from Ligularia muliensis

From the roots of Ligularia muliensis, a novel bieremophilanolide and a new eremophilanolide have been isolated and their structures were elucidated by spectroscopic techniques, including HRMS, IR, UV, 1D-NMR, 2D-NMR, and CD spectra.     

Diversity of Ligularia kanaitzensis in sesquiterpenoid composition and neutral DNA sequences

Twenty-six eremophilane-type sesquiterpenoids, including six new compounds, were isolated from the title species. One of the new compounds, kanaitzensol, suggested the presence of an enzyme for the conversion of eremophil-7(11)-en-8-one derivative to furanoeremophilanes. The plant was collected at 15 locations in Yunnan Province of China and found to be diverse with respect to its sesquiterpenoid composition. DNA sequencing also revealed a large intraspecific diversity of the plant.     

New Sesquiterpenoids from Ligularia duciformis

From the whole plants of Ligularia duciformis, four new sesquiterpenoids, 3β‐acetoxy‐6β‐methoxyeremophila‐7(11),9(10)‐dien‐12,8β‐olide ( 1 ), 3β‐acetoxy‐8α‐hydroxy‐6β‐methoxyeremophila‐7(11),9(10)‐dien‐12,8β‐olide ( 2 ), 3β‐acetoxy‐10β‐hydroxy‐6β,8β‐dimethoxyeremophil‐7(11)‐en‐12,8α‐olide ( 3 ), and 3β‐acetoxy‐6β,8β,10β‐trihydroxyeremophil‐7(11)‐en‐12,8α‐olide ( 4 ) were isolated. Their structures were established by high‐field NMR techniques (¹H,¹H‐COSY, ¹³C‐APT, HMQC, HMBC, and NOESY) and HR‐ESI‐MS analysis, together with comparison of the spectroscopic data with those of structurally related compounds. In addition, the cytotoxicity of the new compounds against human hepatic cancer cells Bel‐7402, human pneumonic cancer cells A‐549, and human colonic cancer cells HCT‐8 were evaluated, the new compounds showed no cytotoxicity against the three tumor cells (all IC₅₀ values >200 μM ).     

Sesquiterpenoids from Ligularia dentata

Five new compounds were isolated from the roots of Ligularia dentata, including four bisabolane‐type sesquiterpenoids, 1 – 4 , as well a new eudesmane, 5 . The previously isolated 3α,6α,9‐tris(angeloyloxy)‐2α,4β‐dihydroxy‐7,11‐epoxybisabol‐10(15)‐en‐5‐one ( 6 ), when left as an oil in a refrigerator over nine months, gave rise to a mixture of two positional isomers, 7 and 8 . Their formation is rationalized by means of epoxide ring opening and shift of an angeloyl (Ang) group. The structures of compounds 1 – 5, 7 , and 8 were established by in‐depth spectroscopic (UV, CD, IR, 1D‐ and 2D‐NMR) as well as mass‐spectrometric methods.     

Isolation of new eremophilane-type sesquiterpenoids, subspicatins A-D and subspicatolide from Ligularia subspicata, and chemical and genetic diversity of the species

New C-1 oxidized eremophilane-type sesquiterpenoids, subspicatins A, B, C, and D, and subspicatolide, were isolated from the root of Ligularia subspicata and their structures were established by spectroscopic and X-ray analyses. Subspicatins A and B were the major components. The species were found to be diverse both in the composition of the root chemicals and in the nucleotide sequences of the internal transcribed spacers (ITS) of the ribosomal RNA gene and the atpB-rbcL intergenic region, but the difference among the samples was not distinct but continuous.     

Sesquiterpenoids and Lactone Derivatives from Ligularia dentata

Seven new compounds were isolated from the roots of Ligularia dentata, including five bisabolane‐type sesquiterpenoids (bisabolane=1‐(1,5‐dimethylhexyl)‐4‐methylcyclohexane), namely (8β,10α)‐8‐(angeloyloxy)‐5,10‐epoxybisabola‐1,3,5,7(14)‐tetraene‐2,4,11‐triol ( 1 ), (8β,10α)‐8‐(angeloyloxy)‐5,10‐epoxythiazolo[5,4‐a]bisabola‐1,3,5,7(14)‐tetraene‐4,11‐diol ( 2 ), (1α,2α,3β,5α,6β)‐1,5,8‐tris(angeloyloxy)‐10,11‐epoxy‐2,3‐dihydroxybisabol‐7(14)‐en‐4‐one ( 3 ), (1α,2α,3β,5α,6β)‐2,5,8‐tris(angeloyloxy)‐10,11‐epoxy‐1,3‐dihydroxybisabol‐7(14)‐en‐4‐one ( 4 ), and (1α,2β,3β,5α,6β)‐1,8‐bis(angeloyloxy)‐2,3‐epoxy‐5,10‐dihydroxy‐11‐methoxybisabol‐7(14)‐en‐4‐one ( 5 ) (angeloyloxy=[(2Z)‐2‐methyl‐1‐oxobut‐2‐enyl]oxy), and two lactone derivatives, (2α,3β,5α)‐2‐(acetyloxy)‐9‐methoxy‐5‐(methoxycarbonyl)‐2,3‐dimethylheptano‐5‐lactone ( 6 ), and (2β,4β)‐2‐ethyl‐5‐hydroxy‐5‐(methoxycarbonyl)‐4,5‐dimethylpentano‐4‐lactone ( 7 ) (α/β denote relative configurations), together with (2E,4R,5S)‐2‐ethylidene‐5‐(methoxycarbonyl)‐4‐methylhexano‐5‐lactone ( 8 ), a known synthetic compound. Compound 2 is the first sesquiterpenoid derivative containing the uncommon benzothiazole moiety. The structures of 1 – 8 were established by spectroscopic methods, especially 2D‐NMR and MS analyses.     

Eremophilane Sesquiterpenoids from Ligularia fischeri

A novel eremophilane dimer, named as fischelactone, and a new sesquiterpene lactam, eremophila‐1(10),7(11),8‐triene‐12,8‐lactam, along with ten known compounds, were isolated from the roots of Ligularia fischeri. Their structures were established by means of spectroscopic analyses (EI‐MS, HR‐ESI‐MS, IR, and 1D‐ and 2D‐NMR data) and X‐ray diffraction study.     

Britanlins A-D, four novel sesquiterpenoids from Inula britannica

A phytochemical investigation on the flowers of Inula britannica has led to the isolation of four novel sesquiterpenoids, britanlins A-D. Britanlins A-C feature the rare presilphiperfolane-type frameworks, which play an important role in biogenesis of triquinane sesquiterpenoids. Britanlin D possessed a rearranged pseudoguaiane skeleton, which was first isolated from nature. The structures of britanlins A to D were elucidated on the basis of extensive spectroscopic methods. The structures of britanlins A and D were further confirmed by single crystal X-ray diffraction.     

Hyrtimomines,indole alkaloids from Okinawan marine sponges Hyrtios spp.

Six new indole alkaloids, hyrtimomines F–K (1–6), were isolated from Okinawan marine sponges Hyrtios spp. The structures of 1–6 were elucidated on the basis of spectroscopic analysis. Hyrtimomine F (1) is a structurally unique bisindole alkaloid possessing an α-keto-?-caprolactam ring, while hyrtimomine G (2) is a symmetrical bisindole alkaloid. Hyrtimomines H–K (3–6) are indole alkaloids possessing β-carboline skeleton with an imidazolium unit. Antimicrobial activities of hyrtimomines F–K (1–6) were evaluated.     

Sesquiterpenoids, alantolactone analogues, and seco-guaiene from the roots of Inula helenium

Three new sesquiterpenoids, a new unusual dimeric eudesmanolide, bialantolactone, a new nor-eudesmanolide, trinoralantolactone, and a new seco-guaiene, 7S,1(10)Z-4,5-seco-guaia-1(10),11-diene-4,5-dioxo, together with 13 known sesquiterpenoids, were isolated from the roots of Inula helenium. Their structures were elucidated by comprehensive spectroscopic analyses. The absolute configurations of bialantolactone and 7S,1(10)Z-4,5-seco-guaia-1(10),11-diene-4,5-dioxo were defined via the experimental and computational optical rotation and CD data. The plausible biosynthetic pathways to bialantolactone and 7S,1(10)Z-4,5-seco-guaia-1(10),11-diene-4,5-dioxo are discussed. 16 compounds were evaluated for their anti-bacterial activities against six bacteria.     

Cytotoxic eremophilane sesquiterpenoids from the saprobic fungus Berkleasmium nigroapicale BCC 8220

Berkleasmins A-E, five new eremophilane sesquiterpenoids were isolated from the saprobic fungus Berkleasmium nigroapicale BCC 8220. The structures of the new compounds were elucidated by analyses of NMR spectroscopic and mass spectrometry data in combination with chemical means. Berkleasmins A and C exhibited cytotoxic activity against cancer cell-lines (NCI-H187, MCF-7, and KB) as well as nonmalignant Vero cells with IC₅₀ values of 1.1-7.5 μg/mL, and these compounds also showed antimalarial activity with respective IC₅₀ of 3.1 and 2.8 μg/mL.     

Protease inhibitors from three fishpond water blooms of Microcystis spp.

Four new natural products, micropeptin GH979 (1), microginin GH787 (2), micropeptin HM978 (3), and micropeptin HA983 (4), as well as 10 known protease inhibitors and hepatotoxins, were isolated from the hydrophilic extract of three samples of cyanobacteria (Microcystis spp.) that were collected from fishponds in Kibbutz Giva’at Haim, Kibbutz Hama’apil, and Kibbutz Gan Shmuel. The structures of the pure natural products were elucidated using spectroscopic methods, including UV, 1D and 2D NMR, and MS techniques. The absolute configuration of the chiral centers of the compounds was determined using Marfey’s method. The inhibitory activity of the compounds was determined for the serine proteases: trypsin, chymotrypsin, thrombin and elastase, and the metalloprotease, aminopeptidase N.     

Sesquiterpenoids from the Rhizome of Ligularia virgaurea

Two novel sesquiterpene dimers, compounds 1 and 2 , were isolated from the rhizome of Ligularia virgaurea, together with the six known sesquiterpenoids 3 – 8 . Their structures were established by physico‐chemical and spectroscopic methods, especially by means of 1D‐ and 2D‐NMR as well as HR‐MS analyses. A mechanism based on a classical Diels–Alder cyclization is proposed for the formation of the dimer 1 from the precursors 8 and the quinone form of 6 (Scheme).     

Two novel diterpenoids from Isodon rubescens var. lushanensis

Two novel diterpenoids, luanchunins A (1) and B (2), along with their precursor, kamebakaurin (3), had been isolated from the stems and leaves of Isodon rubescens var. lushanensis. Their structures were elucidated on the basis of extensive spectroscopic analyses. Compounds 1 and 2 showed potent cytotoxic activity against HL-60 with IC₅₀ values of 4.81 μM and 3.52 μM, respectively. Plausible pathways for the biosynthesis of 1 and 2 were also postulated.