Six new melampolides from Tetragonotheca helianthoides

Chemical analysis of Tetragonotheca helianthoides L. yielded six new melampolide-type sesquiterpene lactones, tetrahelins A–F. All new compounds have the same medium ring skeleton and differ by the ester moieties at C-8 and C-9. Tetrahelin A and B contain the side chain 2-methyl-2,3-diacetoxybutanoate and tetrahelin E 3-hydroxy-3-methylbutanoate. Both ester side chains have previously not been found in sesquiterpene lactones.     

Sesquiterpenoids as chemosystematic markers in the subtribe Hypochaeridinae (Lactuceae,Asteraceae)

Sesquiterpene lactones are well established as chemosystematic markers in the Asteraceae family. From the Lactuceae tribe of the Asteraceae family a large number of sesquiterpene lactones – mainly of the guaiane type – have been isolated. One of the 11 subtribes of the Lactuceae recognized by Bremer is the subtribe Hypochaeridinae, which encompasses 10 genera with approximately 170 species. The present communication summarizes the sesquiterpene derivatives reported from these 10 genera, points out, which constituents are characteristic for particular groups, and discusses the occurrence of these secondary metabolites in a chemosystematic context. To this end, each of the reported sesquiterpenoids reported for the Hypochaeridinae is classified into one of three main compound classes (MCCs; eudesmane-, germacrane-, guaiane-derivatives) and into one of a number of compound classes (CCs) within these principal groups. The distribution of sesquiterpenoids belonging to these particular classes of sesquiterpenoids generally follows the currently accepted generic limits. However, the genus Helminthoteca, which is included into Picris by many authors, possesses an array of compounds implying a closer relationship to the genus Hypochaeris than to the remainder of the genus Picris. Furthermore, Leontodon subgenus Oporinia shows closer similarity in secondary metabolite patterns to the genus Picris than to Leontodon subgenus Leontodon. On the other hand Leontodon subgenus Leontodon has more chemical characters in common with the genus Hedypnois than with Leontodon subgenus Oporinia. These findings are in-line with recent results of molecular analyses, which imply that current generic limits within the Hypochaeridinae might not reflect the phylogeny of the subtribe.     

Weitere isocedren-derivate aus Trixis paradoxa

The investigation of two further species from the tribe Mutisieae afforded in addition to known compounds three new sesquiterpene lactones and two further sesquiterpene esters, all closely related to compounds isolated before from other Trixis species. The isolation of these new substances from Trixis further establishes the chemotaxonomic situation in the subtribe Nassauviinae. From the Dinoseris species, among others, 1β-hydroxyalantolactone was isolated, indicating a relationship to the subtribe Gochnatiinae.     

A revision of Moonia (Compositae,Heliantheae, Coreopsidinae)

The genusMoonia of India and Ceylon, traditionally placed in the subtribe Melampodiinae, is shown to have closer affinities withDahlia andHidalgoa of the subtribe Coreopsidinae. Several morphologically heterogeneous taxa are excluded fromMoonia, and the remaining species,M. heterophylla, is described and illustrated.     

Tetraludin A,B and C,three new melampolides from Tetragonotheca ludoviciana

The investigation of the roots of the four Tetragonotheca species, T. ludoviciana, T. repanda, T. texana and T. helianthoides, resulted in the isolation of the known heptadeca-2-(Z)-8,10-(E)-16-tetraene-4,6-diin-1-ol and its aldehyde derivative from all four species. Aerial parts of T. ludoviciana also contained the acetate of the latter compound as a minor constituent and provided three new melampolide-type sesquiterpene lactones, tetraludin A, B and C.     

Three new melampolide sesquiterpenes,polymatin A,B and C,from Polymnia maculata Cav. var. maculata

Three new melampolide type sesquiterpene lactones were isolated from Polymnia maculata Cav. var. maculata. Their structures were determined by spectroscopic and chemical means. Based on the presently available chemical data, the chemotaxonomic position of Polymnia within the subtribe is discussed.     

Germacranolides from Proteopsis Argentea

Proteopsis argentea (tribe Vernonieae) afforded in addition to known compounds three new sesquiterpene lactones, closely related to those isolated from Eremanthus species, indicating a close relationship between these genera.     

Purification and identification of antimicrobial sesquiterpene lactones from yacon (Smallanthus sonchifolius) leaves

The extraction of yacon [Smallanthus sonchifolius (Poepp. and Endl.) H. Robinson; Asteraceae] leaves and chromatographic separation yielded two new antibacterial melampolide-type sesquiterpene lactones, 8beta-tigloyloxymelampolid-14-oic acid methyl ester and 8beta-methacryloyloxymelampolid-14-oic acid methyl ester, as well as the four known melampolides, sonchifolin, uvedalin, enhydrin and fluctuanin. The newly identified compound, 8beta-methacryloyloxymelampolid-14-oic acid methyl ester, exhibited potent antimicrobial activity against Bacillus subtilis and Pyricularia oryzae, while 8beta-tigloyloxymelampolid-14-oic acid methyl ester showed lower activity. Fluctuanin exhibited the strongest antibacterial activity against B. subtilis among these six sesquiterpene lactones.     

Sesquiterpene lactones from the aerial parts of Anthemis arvensis L.

Two known sesquiterpene lactones, antheindurolides A and B, together with five new related lactones with the same unusual skeleton were isolated from the aerial parts of Anthemis arvensis growing in Serbia. The originally proposed structure of antheindurolide B was revised. This (antheindurolide) type of lactones, detected so far only in the genus Anthemis (Anthemis indurata, Anthemis pseudocotula and Anthemis cotula) could be of chemotaxonomic significance.     

Germacranolides from Lychnophora species

The investigation of three further Lychnophora species and the re-investigation of one species afforded, in addition to known compounds, seven new sesquiterpene lactones all being closely related to those isolated before from the subtribe Lychnophorinae. Furthermore, a new bisabolene diketone was present in one species. The structures were elucidated by spectroscopic methods. The chemotaxonomic situation of the genus is briefly discussed.     

Germacranolides from Eupatoriastrum nelsonii

The aerial parts of Eupatoriastrum nelsonii afforded, in addition to known sesquiterpene lactones, four new lactones all closely related to the germacranolides isolated previously from other genera of the tribe Eupatorieae. The structures were elucidated by spectroscopic methods. Chemotaxonomic aspects are discussed briefly.     

Picridin and dihydropicridin: Revised structures

The structures of dihydropicridin and picridin, two sesquiterpene lactones isolated from Picridiumcristallinum Sch. Bip., are revised. Desacetylmatricarin and ψ-taraxasterol were also obtained from the same plant.     

Sesquiterpene alcohols from Artemisia pygmaea

Artemisia pygmaea Gray contains two sesquiterpene alcohols: the known cryptomeridiol (I) and pygmol (II), a new compound. No sesquiterpene lactones were found in the plant although other species of the section Tridentatae Rydb., with which A. pygmaea has been classified, are usually rich in lactones.     

Sesquiterpene lactones as taxonomic characters in the asteraceae

The Asteraceae is characterized by structurally diverse sesquiterpene lactones and furanosesquiterpenes. In this review the tribal, subtribal and generic distribution of sesquiterpene lactones is examined and the compounds’ utility as taxonomic characters discussed. Sesquiterpene lactones fulfill the major requirements for good analytic and synthetic characters. Studies of infraspecific sesquiterpene lactone variation indicate that different elements within complex taxa are often defined by distinct chemistries, termed chemotypes. Chemotypes have been identified within many of the thoroughly investigated taxa:Ambrosia camphorata, A. chamissonis, A. confertiflora, theA. cumanensis-A. psilostachya-A. artemisiifolia complex,A. dumosa, Artemisia tridentata, Gaillardia pulchella andMelampodium leucanthum. Such an analytic usage is mostly restricted to the infraspecific level. Synthetic usage at the interspecific level and above profits from the application of a biogenetically based methodology for sorting out the complex molecules’ carbon-skeletal and substitutional features into unit characters. Cladistics or Hennigian phylogenetic systematics provides a useful framework for such an analysis. Preliminary surveys indicate that sesquiterpene lactones are especially good characters for differentiating subtribes within several major tribes: the Vernonieae, Heliantheae and Mutisieae. As yet, too few data are available for other tribes to discern such patterns. Species surveys inVernonia, Ambrosia, Iva, Parthenium,Tetragonotheca andArtemisia demonstrate that sesquiterpene lactones are useful in discerning infrageneric groups. The biogenetic cladistic analysis of the interspecific sesquiterpene lactone variation inIva shows the efficacy of this analytical methodology. At present, such biogenetically based approaches are impeded by limited biosynthetic evidence and the erratic distribution of sesquiterpene lactones within the family. Instances of apparent displacement of sesquiterpene lactones by other terpenoids (i.e. sesquiterpene furans, alcohols and acids, diterpenes, diterpene acids, etc.) at various taxonomic levels suggest that ultimately sesquiterpene lactones must be interpreted as taxonomic characters in the context of the family’s total terpene chemistry. All taxa from which sesquiterpene lactones have been reported are listed together with the compound names, major structural features and the literature cited. A less-complete listing is provided for taxa producing furanosesquiterpenes. Structures for all reported compounds are included. Two appendices listing alphabetically taxa and compounds and relevant text page numbers permit cross-indexing of plants and compounds.     

Hirsutinolides,glaucolides and sesquiterpene lactone from Vernonia species

The investigation of nine Vernonia species afforded in addition to known sesquiterpenes 28 new ones. The structures were elucidated by high field ¹H NMR spectroscopy and the configurations were determined by NOE difference spectroscopy and, in one case, by X-ray analysis. The results indicated that configurations of several previously reported sesquiterpene lactones have had to be revised. In addition to known types two new ones, the jalcaguaianolides and the vernojalcanolides, are described. Furthermore some unusual reaction products are presented which, in part, led to some natural occurring lactones.     

Characterization and evolution of secondary metabolites in Brazilian Vernonieae (Asteraceae) assessed by LC‐MS fingerprinting

Tribe Vernonieae are well represented in Brazil, mainly by subtribe Lychnophorinae comprising mostly perennial plants that inhabit arid lands, where species have developed a number of adaptations with recognized ecological protective functions, including secondary metabolite diversification. Recent phylogenetic studies indicate that the subtribe is monophyletic, but questions regarding lineage relationships have yet to be resolved. Phytochemical investigations have also been conducted recently and provide information on the secondary metabolite chemistry of Lychnophorinae. Chemotaxonomic studies have also been carried out. However, these phytochemical investigations are fragmentary and non‐standardized. Therefore, in this study, 15 species representing the major lineages of the subtribe were selected for phytochemical investigation and reconstruction of the ancestral states of their secondary metabolites. The main secondary metabolites of these species were detected by UHPLC‐UV‐MS in different types of extract, showing the presence of trans‐cinnamic acid derivatives, flavonoids, polyacetylenes and sesquiterpene lactones. The ancestral states of these secondary metabolites were reconstructed by parsimony and indicate the occurrence of 12 putative chemical synapomorphies. In this study, we present for the first time phytochemical and evolutionary studies based on the reconstruction of the ancestral chemical character states on a phylogenetic tree of Lychnophorinae.     

Sesquiterpenes from Lactarius blennius

Six sesquiterpene lactones were isolated from Lactarius blennius. The structures of two new sesquiterpenes, blennin A and blennin B were determinated by spectroscopic methods and the structure of the seco-compound, blennin C, is revised. The two known furan sesquiterpenes and lactarorufin A were also identified.     

Sesquiterpene lactones of Podanthus mitiqui

Ovatifolin and two new sesquiterpene lactones, deacetylovatifolin and arturin (1β-hydroxy-8β-angeloyloxy-eudesmane-4(15),11(13)-diene-6α,12-olide, have been isolated from stems and leaves of Podanthus mitiqui. Two of these compounds showed cytotoxic activity.     

Mode of Action of the Sesquiterpene Lactones Psilostachyin and Psilostachyin C on Trypanosoma cruzi

Trypanosoma cruzi is the causative agent of Chagas’ disease, which is a major endemic disease in Latin America and is recognized by the WHO as one of the 17 neglected tropical diseases in the world. Psilostachyin and psilostachyin C, two sesquiterpene lactones isolated from Ambrosia spp., have been demonstrated to have trypanocidal activity. Considering both the potential therapeutic targets present in the parasite, and the several mechanisms of action proposed for sesquiterpene lactones, the aim of this work was to characterize the mode of action of psilostachyin and psilostachyin C on Trypanosoma cruzi and to identify the possible targets for these molecules. Psilostachyin and psilostachyin C were isolated from Ambrosia tenuifolia and Ambrosia scabra, respectively. Interaction of sesquiterpene lactones with hemin, the induction of oxidative stress, the inhibition of cruzipain and trypanothione reductase and their ability to inhibit sterol biosynthesis were evaluated. The induction of cell death by apoptosis was also evaluated by analyzing phosphatidylserine exposure detected using annexin-V/propidium iodide, decreased mitochondrial membrane potential, assessed with Rhodamine 123 and nuclear DNA fragmentation evaluated by the TUNEL assay. Both STLs were capable of interacting with hemin. Psilostachyin increased about 5 times the generation of reactive oxygen species in Trypanosoma cruzi after a 4h treatment, unlike psilostachyin C which induced an increase in reactive oxygen species levels of only 1.5 times. Only psilostachyin C was able to inhibit the biosynthesis of ergosterol, causing an accumulation of squalene. Both sesquiterpene lactones induced parasite death by apoptosis. Upon evaluating the combination of both compounds, and additive trypanocidal effect was observed. Despite their structural similarity, both sesquiterpene lactones exerted their anti-T. cruzi activity through interaction with different targets. Psilostachyin accomplished its antiparasitic effect by interacting with hemin, while psilostachyin C interfered with sterol synthesis.     

Further eudesmanolides and xanthanolides from Telekia speciosa

The re-investigation of the aerial parts of Telekia speciosa afforded five new sesquiterpene lactones, two eudesmanolides and three xanthanolides, all closely related to those isolated before from this species or from related genera. The structures were elucidated by ¹H NMR spectroscopy.