New allo-cedrane type sesquiterpene hemiketals and further sesquiterpene lactones from fruits of Illicium floridanum

Three new tetracyclic sesquiterpene hemiketals possessing the very rare allo-cedrane carbon skeleton, debenzoyl-7-deoxo-1 alpha,7 alpha-dihydroxytashironin, debenzoyl-7-deoxo-7 alpha-hydroxytashironin, and debenzoyl-7-deoxo-7 alpha-hydroxy-3-oxotashironin (1--3), were isolated from the fruits of Illicium floridanum ELLIS (American Star Anise, Star bush). Their structures were elucidated by mass and NMR spectroscopic analyses. The molecular structure of 1, including absolute stereochemistry, was determined by single-crystal X-ray diffraction of its monohydrate. Only one compound of this type, tashironin, has previously been isolated from Illicium tashiroi. Furthermore, a new sesquiterpene lactone of the seco-prezizaane type, 3,4-anhydro-13,14-dihydroxyfloridanolide (4), and the known anislactone B (5) were isolated. The occurrence of further allo-cedrane sesquiterpenes in another Illicium species confirms the hypothesis of previous authors that this type of compound is a biogenetic precursor of the typical seco-prezizaane sesquiterpene lactones found in this genus. Moreover, regarding their co-occurrence with anislactone B as reported here, they may also be considered precursors for the anislactone skeletal type.     

Sesquiterpene lactones from the roots of Ferula varia and their cytotoxic activity

The ethyl acetate-soluble fraction from a MeOH extract of the roots of Ferula varia gave six new sesquiterpene lactones (1-6) and five known sesquiterpenes (7-11). Their structures were established on the basis of spectroscopic evidence. The cytotoxic activities of 1-11 were evaluated against selected human cancer cell lines. Compound 4 showed significant selective cytotoxicity against multidrug-resistant cancer cells (KB-C2). The cytotoxicities of compounds 1, 3, 5, 8, and 11 against KB-C2 cells were enhanced in the presence of nontoxic concentrations of colchicine.     

Terpenoids from Chloranthus serratus and their anti-inflammatory activities

Seven new terpenoids, including two sesquiterpene dimers (1, 2), two norditerpenoids (3, 4), and three sesquiterpenes (5-7), along with six known sesquiterpene dimers and four known sesquiterpenes were isolated from the whole plant of Chloranthus serratus. Their structures and relative configurations were elucidated on the basis of spectroscopic data analysis. The absolute configuration of 1 was determined by the CD exciton chirality method. These isolates were evaluated for their inhibitory effects on lipopolysaccharide-induced nitric oxide production in RAW264.7 cells. Compound 2 and two known compounds, shizukaols B and D, showed significant anti-inflammatory activities, with IC(50) values of 0.22, 0.15, and 7.22 μM, respectively.     

Mitchellenes A-E, cyclic sesquiterpenes from the Australian plant Eremophila mitchellii

Chemical investigations of the Australian plant Eremophila mitchellii resulted in the isolation of the novel tetracyclic sesquiterpene lactones mitchellenes A-C (1-3), the new sesquiterpene acids mitchellenes D and E (4 and 5), and the previously reported natural products 14-hydroxy-6,12-muuroloadien-15-oic acid (6), casticin, and centaureidin. The chemical structures of all compounds were determined by extensive 1D/2D NMR and MS data analysis. Mitchellenes A-C are the first tetracyclic sesquiterpene lactones to be reported; a biosynthetic pathway is proposed for these unique secondary metabolites.     

Decipinin A and decipienolides A and B: new bioactive metabolites from the coprophilous fungus Podospora decipiens

Decipinin A (1), a new compound with antifungal and antibacterial activity, has been isolated from liquid cultures of the coprophilous fungus Podospora decipiens (JS 270). Two new tetracyclic sesquiterpene lactones, decipienolides A (2) and B (3), were also obtained from this isolate as an inseparable mixture of epimers that showed antibacterial activity. The structures of 1-3 were elucidated by analysis of 1D and 2D NMR data, aided by chemical shift comparisons to related compounds.     

New 9-thiocyanatopupukeanane sesquiterpenes from the nudibranch Phyllidia varicosa and its sponge-prey Axinyssa aculeata

Two new 9-thiocyanatopupukeanane sesquiterpene isomers were isolated as major metabolites from the MeOH extract of the sponge Axinyssa aculeata and from its nudibranch predator Phyllidia varicosa. The presence of the sesquiterpenes was monitored by GC-MS, and the structures were confirmed by both 1D and 2D NMR spectroscopy. The isolated sesquiterpenes were found to be toxic toward brine shrimp at LC(50) of 5 ppm. At a dose level of 20 microg, they were found to be weakly and moderately active against B. subtilis and C. albicans, respectively.     

中成药保济丸挥发性化学成分的研究

目的：为了改变中成药羊城“保济丸”的剂型,我们对羊城“保济丸”和香港“保济丸”的挥发性化学成分进行比较研究。方法：应用超声波提取技术分别提取中成药羊城“保济丸”和香港“保济丸”的化学组分,采用气相色谱－质谱联用法鉴定化学成分。通过标准图谱对照确定化合物。峰面积归一化法计算相对百分含量。结果：鉴定出羊城“保济丸”24种化合物,香港“保济丸”20种化合物。结论：羊城“保济丸”倍半萜内酯相对百分含量多于香港“保济丸”,而倍半萜醇类,倍半萜类相对百分含量少于香港“保济丸”。     

Guaiane sesquiterpene lactones and amino acid-sesquiterpene lactone conjugates from the aerial parts of Saussurea pulchella

Two new guaiane sesquiterpene lactones ( 1 and 2) and seven new amino acid-sesquiterpene lactone conjugates ( 3- 9), together with six known sesquiterpene lactones ( 10- 15), were isolated from the methanol extract of the aerial parts of Saussurea pulchella. Their structures were determined on the basis of spectroscopic and chemical methods to be 8alpha- O-(3'-hydroxy-3'-methylbutyryl)desacylcynaropicrin ( 1), 8alpha- O-(2', 3'-dihydroxyisobutyryl)11beta,13-dihydrodesacylcynaropicrin ( 2), and pulchellamines A, B, C, D, E, F, and G ( 3- 9). The structures of the new amino acid-sesquiterpene lactone conjugates, pulchellamines A, B, C, D, E, F, and G ( 3- 9), were confirmed by synthesis. The isolated compounds were evaluated for cytotoxic activity against four human tumor cell lines. Compounds 11 and 12 exhibited cytotoxicity against skin melanoma (SK-MEL-2) and ovary malignant ascites (SK-OV-3) human tumor cell lines with ED 50 values of 1.53 and 4.07 microM, and 2.49 and 7.42 microM, respectively.     

cis,cis-Germacranolides and melampolides from Mikania thapsoides

The aerial parts of Mikania thapsoides afforded six new cis,cis-germacranolide-type sesquiterpene lactones (1-6), of which three (1-3) have an unusual 3,4-epoxy function, and also afforded two new melampolides (7 and 8). All compounds have a trans C-8 lactone ring closure. Their structures were elucidated using 1D and 2D NMR measurements, and the absolute configuration of 1 was determined using the Mosher ester method.     

Cytotoxic sesquiterpene lactones from Vernonia pachyclada from the Madagascar rainforest

Bioassay-guided fractionation of the cytotoxic leaf extract of Vernonia pachyclada Baker led to the isolation of three new sesquiterpene lactones, designated glaucolides K-M (1-3). The structures of the new compounds were determined using 1D and 2D NMR spectroscopy, and the structure and stereochemistry of 1 were confirmed by single-crystal X-ray diffraction. Compound 3 showed moderate activity in the A2780 human ovarian cancer cell line, with an IC50 of 3.3 microM.     

Cytotoxic action of alpha-methylene lactones towards HeLa cells in culture

Possible targets to account for the qtotoxic activity of the a-methylene containing sesquiterpenes elephantopin and vernoleph, and an a-methylene-lactone steroidal derivative, 3-methoxy-16-methylene-17-oxo-17a-D homoestra-1,3,5,(10)-triene, have been studied. The compounds reduced surface and intracellular thiol levels in HeLa S3 ceb, caused an inhibition of Na+/K+-ATPase and an inhibition of the incorporation of [³H]thymidine into macromolecules. In addition, the steroidal compound, but not the sesquiterpene elephantopin, released lysosomal enzymes and caused marked changes in the structural integrity of the cells. Observed effects of α-methylene lactones on cellular respiration and [³H]thymidine uptake were not a consequence of alkylation. The results support the concept of the cell membrane and in particular Na⁺/K⁺-ATPase as a target for sesquiterpene lactone alkylation.     

Sesquiterpenes from the Formosan stolonifer Tubipora musica.

Eight new sesquiterpenes, tubipolides A-G (1-7) and tubiporone (8) (novel carbon skeleton), and a known sesquiterpene, spirotubipolide, have been isolated from the Formosan stolonifer Tubipora musica. The structures of compounds 1-8 were determined by 1D and 2D NMR spectral analysis.     

Phytochemistry and antifungal properties of the newly discovered tree Pleodendron costaricense

Gas chromatography analysis of the essential oils of leaves and bark collected from the newly discovered tree Pleodendron costaricense identified alpha-pinene, beta-pinene, beta-myrcene, beta-thujene, and beta-caryophyllene as their major constituents. Phytochemical analysis of P. costaricense parts led to the isolation and identification of delta-tocotrienol, beta-sitosterol, four known drimane-type sesquiterpenes, cinnamodial (1), cinnamosmolide (2), polygodial (3), and mukaadial (4), and two new compounds, a drimane-type sesquiterpene, parritadial (5), and an eremophilane-type sesquiterpene, pleodendione (6). Antifungal assays with the two major compounds, 1 and 2, were carried out, and results showed a high activity of 1 against Alternaria alternata (MIC = 3.9 microg/mL), Candida albicans azole-resistant strain D10, and Wangiella dermatitides (MICs = 15.6 microg/mL). Compound 2 showed less potent antifungal activities than 1 but was more effective against Candida albicans azole-resistant strain CN1A (MIC = 23.4 microg/mL) and Pseudallescheria boydii (MIC = 78.1 microg/mL). A combination of the dialdehyde sesquiterpenes with dillapiol showed a synergistic antifungal effect with 1 and an additive effect with 4 and 5.     

An approach to the genus Tanacetum L. (Compositae): Phytochemical and pharmacological review

In view of the importance in folk medicine of some species of Tanacetum L. (Compositae), e.g. T. parthenium, this paper reviews reports of the past two decades on their phytochemistry and pharmacological actions. The facets of phytochemical composition to be reviewed concern mainly the compounds with a chemosystematic interest in the tribe: terpenoids, especially sesquiterpenes and sesquiterpene lactones and flavonoids. The pharmacological activities which make it possible to corroborate their use as a herbal remedy have also been reviewed.     

Cytotoxic sesquiterpene lactones from the root of Saussurea lappa

Bioassay-directed fractionation of Saussurea lappa led to the isolation of a novel lappadilactone (1) and seven sesquiterpene lactones (2-8) as cytotoxic principles against selected human cancer cell lines. Lappadilactone (1), dehydrocostuslactone (2), and costunolide (5) exhibited the most potent cytotoxicity with CD50 values in the range 1.6-3.5 microg/mL in dose- and time-dependent manners. The cytotoxicities were not specific and showed similar activities against HepG2, OVCAR-3 and HeLa cell lines. The structure-activity relationship showed that the alpha-methylene-gamma-lactone moiety is necessary for cytotoxicity, and activity is reduced with the presence of a hydroxyl group. In addition, seven noncytotoxic compounds (9-15) were also isolated, including two novel sesquiterpenes, a guaianolide-type with a C17 skeleton, lappalone (13), and 1beta,6alpha-dihydroxycostic acid ethyl ester (14). The structures of the new compounds were elucidated from spectroscopic and/or X-ray data interpretations. Some representative compounds were also tested for antibacterial activity; however, only marginal activities were observed. Therefore, compounds 1-8 are potential cytotoxic agents but without significant antibacterial effect.     

Sesquiterpenes from Stems of Syringa pinnatifolia var. alashanensis

Objective To study the chemical constituents of the volatile oil from the stems of Syringa pinnatifolia var.alashanensis.Methods The volatile oil from the stems of S.pinnatifolia var.alashanensis was obtained by steam distillation.They were isolated by chromatography on silica gel,Sephadex LH-20 columns and TLC,etc.The structures were elucidated by spectroscopic methods,including extensive 1D and 2D NMR techniques.Results Five sesquiterpenes were isolated from the volatile oil.Conclusion Compound 1 is a new sesquiterpene.     

Sesquiterpene lactones from Anthemis altissima and their anti-Helicobacter pylori activity

Seven sesquiterpene lactones, (-) sivasinolide (1), a new naturally occurring eudesmanolide (altissin, 2), desacetyl-beta-cyclopyrethrosin (3), tatridin-A (4), 1-epi-tatridin B (5), 1alpha,10beta-epoxy-6-hydroxy-1,10H-inunolide (6), and spiciformin (7), were isolated from Anthemis altissima. Also isolated were 10 known flavonoids, namely, apigenin (8), kaempferol 4'-methyl ether (9), quercetin (10), quercetin 3-methyl ether (11), isorhamnetin (12), rhamnetin (13), 6-hydroxyquercetin 3,6,4'-trimethyl ether (14), isoquercetrin (15), taxifolin (16), and eriodictyol (17), and one phenolic acid, chlorogenic acid (18). The structure and the stereochemistry of compound 2 were deduced by spectroscopic methods. The in vitro activity of the sesquiterpene lactones (1-5) against Helicobacter pylori, as well as against three Gram-positive and three Gram-negative bacteria growing aerobically, was tested using the microdilution method. Compounds 8-18 have also been tested against H. pylori.     

Flavones and sesquiterpene lactones from Achillea atrata subsp. multifida: antimicrobial activity.

Four flavones (1-4) and nine sesquiterpene lactones (5-13), one of them (5) a new compound, were isolated from the aerial parts of Achillea atrata L. subsp. multifida. Although the crude extract demonstrated in vitro inhibitory activity against Candida albicans and Bacillus subtilis, all isolated flavones were active against B. subtilis. Flavones 1, 2, and 3 were also active against C. albicans, while 1 and 3 exhibited activity against E. coli, as well. None of the tested lactones (7, 9, 12, and 13) showed any antimicrobial activity.     

Sesquiterpene lactones from Staehelina fruticosa

The phytochemical analysis of Staehelina fruticosa led to the isolation of four germacranolide-type sesquiterpene lactones (1- 4), including two new glycosides. The structures of these sesquiterpene lactones were elucidated using spectroscopic techniques, and enzymatic hydrolysis was carried out to confirm the nature of the two glycoside derivatives. Molecular modeling was incorporated to substantiate their relative configuration.