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The aerial parts of Stevia vaga afforded four new guaianolides, four new germacranolides, one new melampolide and three new heliangolides as well as two known flavones. The structures were established mainly by NMR spectroscopy.

Aerial parts of Stevia maimarensis afforded two known and six new germacradienolides as well as one known and two new eudesmanolides. Aerial parts of Synedrellopsis grisebachii furnished only previously known compounds and no sesquiterpene lactones.

An extract of the aerial parts of Inula salsoloides afforded in addition to known compounds an eudesmanolide, two melampolides and two linear sesquiterpenes. The structures and spectroscopic data of two germacranolides are revised

Investigation of the aerial parts of Mikania mendocina yielded, in addition to known quadrangolide, two new 15-norguaianolides, a new guaianolide and three new germacranolides. The structure of a germacranolide isolated from M. dusenii has been revised.

The spatial structure of 1(10)Z, 4Z-hanphyllin has been established by the x-ray method. A new conformation of the ten-membered ring in Z, Z-germacranolides has been found - the15 D 5,1 D 14 boat-boat type. The probabilities of the realization of the conformers of this compound and of its C3-epimer have been calculated by the method of molecular mechanics.

Acid-catalyzed cyclization of the natural germacranolide gallicin (8) yielded, among other products, the 1,4-epoxyeudes-manolide 9, which has a trans-fused decaline system. Under the same conditions the closely related germacranolide shonachalin A (8α-hydroxygallicin) (3) cyclized to the eudesmanolide 4 with a cis fused decaline system. The structures of these cyclization products were secured by means of chemical correlations and X-ray diffraction analyses.

A new germacranolide [1] was isolated from the aerial parts of Tanacetum densum ssp. sivasicum (Compositae), a species endemic to Turkey.

Aerial parts of Mikania ypacarayensis afforded, in addition to mikanolide and related known sesquiterpene dilactones, three new dilactones, a derived lactone hydroxy ester and a known germacranolide.

Leaves of Montanoa karwinskii afforded in addition to known sterols, triterpenes and kaurane derivatives, four germacra-12,6β-olides. Three were new compounds, karwinsinolides A, B and C. Their structures were established by spectral methods, mainly NMR. A new seco-caryophyllene derivative was also isolated.

International audience; Fractionation of the dichloromethane extract of Centaurea tougourensis (Boiss. and Reut.) led to the isolation of four sesquiterpene lactones: an elemanolide (1), a germacranolide (2) and two heliangolides (3, 4), the latter being identified for the first time from natural source

In a two-microelectrode voltage clamp assay using Xenopus laevis oocytes, a petroleum ether extract prepared from a commercial sample of the traditional Chinese herbal drug labelled as " Chaihu" (Bupleurum chinense DC. roots) enhanced the I(GABA) by 156 % ± 22 % when tested at 100 µg/mL. By means of HPLC-based activity profiling combined with high-resolution LC-MS and microprobe NMR, the germacranolide aristolactone was identified as one of the main active compounds (EC₅₀ 56.02 µM ± 5.09 µM). However, aristolactone has been previously reported only from the genus Aristolochia (Aristolochiaceae), suggesting a possible adulteration. With the aid of a validated HPTLC protocol for detection of aristolochic acids and with reference samples, the commercial sample was confirmed to be a mixture of Aristolochia manshuriensis root and Bupleurum chinense root. This finding was corroborated by macroscopic inspection of the drug. This case of adulteration with a highly nephrotoxic drug raises concerns about adequate quality control of TCM drugs commercialized in Europe.

The aerial parts of two Andryala species yielded several guaianolides and guaianolide glycosides, three of them being new. The aerial parts of Urospermum dalechampii yielded several known germacranolides and the new dihydroflavonol 3- O -methyltaxifolin.

The flowers of Tanacetum argenteum subsp. argenteum yielded two new germacranolides, in addition to some known sesquiterpene lactones. The structures were elucidated by spectral methods and chemical transformations. 8α-Angeloyloxycostunolide showed cytotoxic activity and antifeedant activity against neonate larvae of Spodoptera littoralis .

The authors describe in full the elucidation of complete structures of guaianolide and germacranolide lactones, isolated from some species of genera Centaurea L., Chartolepis CASS. and others belonging to subtribe Centaureinae DUMORT. The structures were determined mainly on the basis of detailed analysis of 1H NMR and CD spectra. The structure of linichlorin B (XV) was determined by X-ray diffraction analysis.

Based on a survey of remedies used in Renaissance Europe to treat malaria, we prepared and screened a library of 254 extracts from 61 plants for antiplasmodial activity in vitro. HPLC-based activity profiling was performed for targeted identification of active constituents in extracts. One of the most remarkable results was the identification of onopordopicrin, a germacranolide sesquiterpene lactone isolated from Arctium nemorosum as a potent inhibitor of P. falciparum with an IC(50) of 6.9 μM. It was tested similarly against Trypanosoma brucei rhodesiense, the parasite which causes African sleeping sickness. With an IC(50) of 0.37 μM, onopordopicrin was one of the most potent natural products reported so far. Cytotoxicity was determined against rat myoblast L6 cells (IC(50): 3.06).

Enantiomerically pure (+)-vemolepin was semi-synthesized for the first time using the synthon (6S,7R,8S)-8,14-diacetoxy-15-hydroxygermacra-1(10),4,11(13)-trien-6, 12-olide [(+)-minimolide], the major sesquiterpene lactone of the Argentinean vine Mikania minima. After performing four consecutive reactions (Cope rearrangement, two oxidations, and selective hydrolysis of the acetate groups) on the synthon (+)-minimolide, a (+)-vernolepin yield of ca. 40% was achieved, proving to be a suitable semi-synthetic strategy for the production of quantities between 0.5-1.0 g of (+)-vernolepin. The transformations described here mimetize the biogenetic pathway for the production of (+)-vernolepin in the genus Vernonia. The synthesized (+)-vernolepin, but not its precursors, shows antifungal activity similar to amphotericin B. The semi-synthesis reported here combines affordable and easily available chemical reagents with classical organic methodologies. Fil: Bach, Sandra M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; Argentina Fil: Díaz, Fernando R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; Argentina Fil: Bach, Horacio. University of British Columbia; Canadá Fil: Catalan, Cesar Atilio Nazareno. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto de Química del Noroeste. Universidad Nacional de Tucumán. Facultad de Bioquímica, Química y Farmacia. Instituto de Química del Noroeste; Argentina

A germacranolide sesquiterpene lactone, 2α,5-epoxy-5,10-dihydroxy-6α-angeloyloxy-9β-(3-methylbutyloxy)-germacran-8α,12-olide (EDAG), isolated from Carpesium triste var. manshuricum , showed inhibitory activity in the production of nitric oxide (NO) and the expression of inducible nitric oxide synthase (iNOS) mRNA and protein in LPS-activated macrophage cells. Molecular analysis reveals that these suppressive effects are correlated with the inhibition of NF-κB activation by EDAG. Immunoblotting showed that EDAG suppressed the LPS-induced degradation of I-κBα and decreased nuclear translocation of p65. Futhermore, EDAG showed reduced phosphorylation of ERK1/2 and p38 MAPK, whereas activation of JNK was not changed. These data suggest, at least in part, that EDAG utilizes the signal cascades of ERK1/2, p38 MAPK, and NF-κB for the suppression of iNOS gene expression.

The aerial parts of Artemisia turcomanica and A. deserti yielded two new germacranolides, a new guaianolide, and several known mono- and sesquiterpenes.

In addition to neoliacine and neoliacinic acid previously reported, three new germacranolides, named neoliacinolide A, B, and C, were isolated from the leaves of Neolitsea aciculata Koidz., and their structures were elucidated by spectroscopic analysis.

Arucanolide is a germacranolide, isolated from the dichloromethane leaves' crude extract. Germacranolides are frequently described as responsible for antiproliferative activities with apoptosis induction. Therefore, study of anticancer activity of C. pinnatifida extracts and substances became important. This compound was identified as involved with the antiproliferative activity by bio-guided assays evaluated in nine different tumor and one normal cell lines. Samples were tested in a concentration range from 0.25 to 250μg/ml and activity was measured by sulforrodamine B method and total growth inhibition was calculated by non linear regression. The most potent fraction showed high selectivity for melanoma (TGI5: 1,04μg/mL; TGI6: 1,07μg/mL) and kidney (TGI5: 1,45μg/mL; TGI6: 1,32μg/mL) cancer cell lines. The dichloromethane leaves' crude extract demonstrated In vivo activity when evaluated in solid and ascitic Erhlich tumor assay. Purification of this fraction by column chromatography afforded Arucanolide that was identified by comparison of the spectral data with literature [1].

A new germacranolide has been isolated from the aerial parts of Artemisia pallens and the structure was established as 4,5β-epoxy-10α-hydroxy-1-en-3-one-trans-germacran-6α,12-olide by critical comparison with tagitinin C and spectral analysis.

An extract of whole plants of Achillea santolina afforded a new guaianolide and a new germacranolide in addition to two known guaianolides and three flavonoids. Structures were elucidated by spectroscopic methods, and the structure of the germacranolide was confirmed by a single crystal X-ray analysis.

The aerial parts of Vicoa indica afforded a new sesquiterpene lactone as its acetate (1) the structure and relative stereochemistry of which was established by spectral data including X-ray crystallographic analysis.

Six new sesquiterpene lactones, scorzoaustriacoside (1), scorzoaustriacin (2), scorzoaustriacin 3-O-beta-d-glucoside (3), 4-epi-dihydroestafiatol (4), 14-isovaleroxyscorzoaustricin (5), and 14-isovaleroxyscorzoaustricin sulfate (6), along with five known guaianolides, were isolated from an acetone extract of the roots of Scorzonera austriaca. The structures of the new compounds were elucidated mainly by interpretation of their 1D and 2D NMR and HRMS data. Several isolates obtained in this investigation were evaluated against a small panel of cancer cell lines.

Nine sesquiterpene lactones, anthemin A (1), 1 alpha-hydroxydeacetylirinol-4 alpha,5 beta-epoxide (2), anthemin C (3), tatridin A (4), 1-epi-tatridin B (5), anthemin B (6), 6-deacetyl-beta-cyclopyrethrosin (7), elegalactone A (8), and 1 beta,4 alpha,6 alpha-trihydroxyeudesm-11-en-8 alpha-12-olide (9), were isolated front the aerial parts of A. melanolepis in addition to eight known flavonoids and three phenolic acids. Compounds 1, 3, and 6 are new natural products. The structures of the compounds were deduced by spectroscopic methods. The in vitro antimicrobial potential of the isolated sesquiterpene lactones four Gram-positive and five Gram-negative bacteria and One fungus was evaluated using the against microdilution method, and their in vitro cytotoxic activity was determined against a panel of human tumor cell lines. Furthermore. The pharmacokinetic profile Of the sesquiterpene lactones was investigated using computational methods. ESF (European Social Fund); National Resources [70/3/7171]

The aerial parts of Lecocarpus lecocarpoides afforded in addition to the known lecocarpinolide A, 15-hydroxy-8β-2′-methylbutyryloxy-14-oxo-4,5- cis -acanthospermolide and 3′,4′-di- O -methyleupalitin, four new melampolides, the lecocarpinolides I–K, and M and the new cis , cis -germacranolide lecocarpinolide L. Structures and their stereochemistry were elucidated by spectral methods and chemical transformations.

The stereochemistry as well as the conformation of two germacranolides and two 3,4-epoxyguaianolides were determined by computational methods employing LAOCOON-III and DAERM programs. The chair-chair conformation was shown to be preferred by the germacranolide macrocycle in solution, while the A-ring of 1,10-dehydro-3,4-epoxyguaianolides was shown to be approximately planar. The ten-membered ring stereochemistry of germacranolides was deduced from the calculated results.

The aerial parts of Centaurea calcitrapa yielded cnicin, cnicin 4′-acetate, melitensin, a related elemanolide, the two new germacranolides 11α,13- and 11β,13-dihydrosalonitenolide, and the lignans arctigenin, pinoresinol and 7′( S )-hydroxyarctigenin. The latter compound is described for the first time as a natural product. The aerial parts of Centaurea pabotii yielded 11,13-dihydrodeacylcynaropicrin, aguerin A and a new guaianolide related to cynaropicrin.

A collection of 12 natural and synthetic sesquiterpene lactones with eudesmanolide, melampolide, cis,cis -germacranolide, and guaianolide skeletons have been prepared and tested as allelochemicals. The effect of a series of aqueous solutions at 10 −4 -10 −9 M ofthis collection is evaluated. The specific structural requirements related to their activity is discussed. The natural sesquiterpene lactones soulangianolide A, melampomagnolide A and B, zaluzanin C and isozaluzanin C have been synthesized from costunolide, parthenolide and dehydrocostuslactone using SeO 2 and tert -butylhydroperoxide. The structures of the synthetic compounds were established by NMR spectroscopy.

Extraction of the aerial parts of Stevia jujuyensis afforded a sesquiterpene lactone with a new carbon skeleton apparently formed by biological rearrangement of a 4-epitansanine derivative as well as the 4-epitansanin derivative itself, two new heliangolides, a new germacradienolide and jaceosidin.

Several acyl derivatives of cnicin were obtained through lipase-catalysed acylation and alcoholysis reactions. In most reactions lipases showed a regioselective behaviour affording only one product. Longer chain acyl derivatives were prepared at lower temperature than the used in lipase-catalysed reactions, to preclude side products formation. The enzymatic approach let to prepare a family of novel acetyl and fatty acid derivatives of cnicin which are not obtainable following traditional organic synthetic procedures. Fil: Monsalve, Leandro Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina Fil: Rosselli, Sergio. Università di Palermo; Italia Fil: Bruno, Maurizio. Università di Palermo; Italia Fil: Baldessari, Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Unidad de Microanálisis y Métodos Físicos en Química Orgánica. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Unidad de Microanálisis y Métodos Físicos en Química Orgánica; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina

From the aerial parts of Salvia castanea Diels f. tomentosa Stib., four new hemiketal germacranolide sesquiterpenoids, castanins C-F (1 -4), were obtained as two pairs of interconvertible forms along with their acetates, 5 and 6. Their structures were elucidated by spectroscopic methods and X-ray analysis of the uninterconvertible isomeric acetates, 5 and 6. The computational study explained that the ratios of 1 and 2, 3 and 4, and their acetates (5 and 6) in the mixtures were 1:1, 1:2, and 1:3, respectively. In addition, the semisynthesis of castanins C (1) and D (2) was conducted by the photooxidation of castanin B (8), the major constituent of this plant. Compounds 5, 6, and 8 were also tested for their inhibitory activity toward MCF-7, HeLa, and HepG2 cell lines. (C) 2008 Elsevier Ltd. All rights reserved.

The results of the chemical modification of stizolicin, a sesquiterpene lactone of the trans,trans-germancrane type and, in particular, the epoxidation, saponification, and acetylation of its molecule are discussed. On the basis of the results of an x-ray structural experiment, for 6-acetoxy-13-methoxy-1,10-epoxystizolicin we propose the structure of 6α-acetoxy-13-methoxy-1,10: 4,5-diepoxy-1,5,7α(H),8,11β(H)-E,E-germacr-8,12-olide.

The new germacranolide argolide has been isolated from the epigeal part ofArtemisia glabella, and its structure has been shown by its conversion into oxopelenolide B. From the results of an x-ray investigation it is suggested that argolide has the spatial structure of 3-oxo-4α,7α,6β(H)-germacra-1(10),11(13)-dien-6,12-olide.

Extraction of aerial parts of Artemisia barrelieri and chromatographic separation yielded a new germacranolide, two new monocyclic sesquiterpenes and a novel germacranolide dimer, together with several known compounds.

The aerial parts of Jurinea leptoloba afforded, in addition to the known germacranolides albicolide, salonitenolide, pectorolide, jurinelloide and its 20-hydroxy derivative, four new melampolides, two elemanolides, 1β-hydroxy-β-costol glucopyranoside and dihydrosyringenin. The structures were elucidated by high field NMR techniques.

From the aerial parts of Siegesbeckia orientalis , in addition to a known sesquiterpene lactone, nine new germacranolides, three melampolides, three geranylnerol derivatives and three ent -pimarenes were isolated. From Guizotia scabra a new eudesmanolide was obtained. The structures were elucidated by high field NMR techniques. The chemotaxonomic aspects are discussed briefly.

The aerial parts of Stevia grisebachiana afforded, in addition to estafietin, 11αH,13-dihydroestafietin, dehydroleucodin, 10- epi -8-deoxycumambrin, hanphyllin and loliolide, seven new guaianolides and one new germacranolide. The structure of the latter, 4-epitansanin, was confirmed by X-ray analysis.

The aerial parts of Artemisia ludoviciana afforded, in addition to more widespread compounds and several known sesquiterpene lactones, three new germacranolides, two guaianolides, four secoguaianolides and a monoterpene. A new rearrangement of a hydroperoxide is described. Structures were elucidated by high field NMR techniques.

Four new germacranolides, two new guaianolides and a new pinguisane-type sesquiterpene alcohol have been isolated from the pungent liverwort Porella acutifolia subsp. tosana , together with the previously known sesquiterpenoids, 4α,5β-epoxy-8- epi -inunolide and porelladiolide and diterpene dialdehyde, perrottetianal. Their structures were characterized by spectral data and chemical transformation. The hot taste of the species is due to the presence of 1α- and 1β-hydroperoxy-4α,5β-epoxygermacra-10(14),11(13)-dien-12,8-olides. Porella acutifolia subsp. tosana is classified as chemotype IV (pinguisane—germacrane/guaiane—sacculatane-type) of the Porellaceae.

The aerial parts of Hymenoxys linearifolium afforded, in addition to four known pseudoguaianolides, 12 new ones: a germacranolide, a guaianolide, five esterified glucopyranosides of 9-hydroxy-γ-geraniol and two glucopyranosides esterified with 2-methylbutyric and E - and Z-p -coumaric acid, respectively. The structures were elucidated by high field NMR techniques.

The aerial parts of Brickellia californica afforded in addition to widespread compounds seven guaianolides, three of them not reported previously, and a germacranolide. From B. lemmonii 11 new ent -labdanes and three known ones were isolated. Structures were elucidated by high field NMR techniques.

The aerial parts of Cronquistia pringlei afforded, in addition to some known germacranolides and guaianolides, four new guainolides a lactone with a new carbon skeleton, i.e. a heliangolide with a cyclopropane ring. The structures were elucidated by high field NMR techniques. The chemotaxonomy is discussed briefly.

The whole plants of Carpesium triste var. manshuricum afforded two known and two new germacranolides, 2α,5-epoxy-5,10-dihydroxy-6α-angeloyloxy-9β-(2-methylbutyloxy)-germacran-8α, 12-olide and 2α,5-epoxy-5,10-dihydroxy-6α-angeloyloxy-9β-(3-methylbutyloxy)-germacran-8α, 12-olide. Their structures were established by physicochemical and spectroscopic methods.

Radix Inulae is used as a gastric and antibacterial agent in traditional Chinese and Tibetan medicines. Most of its chemical constituents have been identified and include a series of sesquiterpenes with various carbon skeletons such as: eudesmanolide, elemanolide, germacranolide, sesquicaranolide, guaianolide and humulane. Certain organic solvent fractions and sesquiterpenes from Radix Inulae have been found to significantly inhibit the growth of tumor cell strains in vitro. They also show antibacterial, cardiovascular and hypoglycaemic as well as insulin-sensitization activities. The present review summarizes research on the chemistry and biological activity of Radix Inulae.

The fundamental study of the biogenetic origin of natural products has always been limited from the experimental point of view because proposed reaction mechanisms have only been supported on the molecular structures of reagents and the reaction products. In a seminal contribution, Ortega and Maldonado (Ortega, A.; Maldonado, E. Heterocycles, 1989, 29, 635-638.) described an experiment relevant for the development of the biogenetic theory of sesquiterpene lactones. They were able to obtain the one-pot transformation of a pseudoguaianolide sesquiterpenic lactone from a germacranolide using bentonitic earth as the catalyst. This transformation involved two steps in the biogenesis of these compounds (germacranolide --> guaianolide --> pseudoguaianolide) and is significant because when Bronsted or Lewis acids are used, it is only possible to isolate the product of the next step of the biogenesis. The results presented here support the biogenetic theories by Hendrickson and Fischer and question the concerted nature of the Herz proposal. Some questions about the mechanisms still remain unanswered; mainly because it was only possible to isolate a few stable byproducts. Using the third generation functional mPWB95 developed by Truhlar, it was possible to study the mechanisms associated with the biogenesis of pseudoguaiananolides. Its application can explain the origin of all the byproducts obtained in the original experiment and establish the validity of the original biogenetic hypothesis. The performance of the above-mentioned functional was compared to B3LYP, B97-2, and B1B95 functionals and the MP2 method, finding that mPWB95 competes successfully with all the latter in both, the determination of the magnitude of the activation energies and the ability to map the potential energy surface. Therefore, the mPWB95 method can be considered good to deal with this type of study.