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.     

Sesquiterpene lactone stereochemistry influences herbivore resistance and plant fitness in the field

Background and Aims

Stereochemical variation is widely known to influence the bioactivity of compounds in the context of pharmacology and pesticide science, but our understanding of its importance in mediating plant–herbivore interactions is limited, particularly in field settings. Similarly, sesquiterpene lactones are a broadly distributed class of putative defensive compounds, but little is known about their activities in the field.

Methods

Natural variation in sesquiterpene lactones of the common cocklebur, Xanthium strumarium (Asteraceae), was used in conjunction with a series of common garden experiments to examine relationships between stereochemical variation, herbivore damage and plant fitness.

Key Results

The stereochemistry of sesquiterpene lactone ring junctions helped to explain variation in plant herbivore resistance. Plants producing cis-fused sesquiterpene lactones experienced significantly higher damage than plants producing trans-fused sesquiterpene lactones. Experiments manipulating herbivore damage above and below ambient levels found that herbivore damage was negatively correlated with plant fitness. This pattern translated into significant fitness differences between chemotypes under ambient levels of herbivore attack, but not when attack was experimentally reduced via pesticide.

Conclusions

To our knowledge, this work represents only the second study to examine sesquiterpene lactones as defensive compounds in the field, the first to document herbivore-mediated natural selection on sesquiterpene lactone variation and the first to investigate the ecological significance of the stereochemistry of the lactone ring junction. The results indicate that subtle differences in stereochemistry may be a major determinant of the protective role of secondary metabolites and thus of plant fitness. As stereochemical variation is widespread in many groups of secondary metabolites, these findings suggest the possibility of dynamic evolutionary histories within the Asteraceae and other plant families showing extensive stereochemical variation.     

Distribution of chromenes and benzofurans in Encelia californica

Two populations of Encelia californica (Asteraceae) were analysed for chromenes and benzofurans on an organ specific basis using HPLC. Both classes of compounds were present in all parts of the plant studied including roots, stems, leaves, capitula and achenes. The distribution patterns were less complex in roots and achenes when compared to stems, leaves and capitula which yielded three chromenes and two benzofurans. In addition to the chromenes and benzofurans the capitula afforded a sesquiterpene lactone of the eudesmanolide type which was absent in the other parts of the plant.     

Variation of sesquiterpene lactones in Lactuca aculeata natural populations from Israel,Jordan and Turkey

A comparative phytochemical study of seven sesquiterpene lactones in natural populations of the wild lettuce Lactuca aculeata Boiss. (Asteraceae) was performed, based on 23 accessions derived from eight, two, and single localities from Israel, Jordan, and Turkey, respectively. The compounds were profiled and quantified in leaves and roots of the plants, grown from achenes (cypselas) in a greenhouse under controlled conditions, using reverse phase HPLC with on-line photodiode array detector. In the present study, L. aculeata was confirmed as a taxon strongly characterized by four dominant sesquiterpene lactones: 8-deoxylactucin, jacquinelin, crepidiaside B and lactuside A. An analysis of quantitative results of these four constituents led to the following conclusions: (i) the sesquiterpene lactone contents varied significantly, mainly within the populations; however, for two variables (crepidiaside B and lactuside A in root samples) the contents varied mostly between populations, (ii) these differences are likely to be genetically controlled since all accessions were grown under standardized glasshouse conditions. Accessions containing high levels of some sesquiterpene lactones were found in several populations. These traits should be conserved in situ and ex situ and utilized in further research and lettuce improvement.     

New germacrolide- and heliangolide-type sesquiterpene lactones from Melampodium linearilobum

Chemical analysis of Melampodium linearilobum yielded, besides coumarin, seven germacrolide-type sesquiterpene lactones, linearilobin A to G and two heliangolides, linearilobin H and I. All new sesquiterpene lactones are oxygenated at C-14 and C-15 and differ by the number and types of ester moieties at C-8, C-14 and C-15. M. linearilobum represents the first species within the genus known to produce germacrolides and heliangolides instead of the more common melampolides.     

Antifungal activity of sesquiterpene lactones

Forty-five sesquiterpene lactones were screened for their antifungal activities against Microsporum cookei, Trichophyton mentagrophytes and Fusarium sp. The screening tests showed that a majority of sesquiterpene examined possess at least weak antifungal activity, the eudesmanolides being the most active. The antifungal activity of sesquiterpene lactones cannot be explained by the presence or absence of two potential active sites (the exocyclic methylene and, in pseudoguaianolides, a β-unsubstituted cyclopentenonel) but other functions must play a role in enhancing or reducing this activity.     

Allenic germacranolides,bourbonene derived lactones and other constituents from Vernonia species

An investigation of seven Vernonia species, mainly from northern Brazil, afforded in addition to known compounds three new unusual sesquiterpene lactones with an allenic group. Intensive NMR studies fully established the structures. Furthermore, two lactones derived from bourbonene, two new glaucolides, a new furansesquiterpene, a nerolidol derivative and two other sesquiterpenes derived from eudesmane were isolated. The biogenetic relationships of the sesquiterpene lactones present in Veronia species as well as the chemotaxonomic aspects are discussed.     

The chemical composition of the litter and soil in a community of Artemisia tridentata ssp. vaseyana

The leaves, litter, and soil from within a community of Artemisia tridentata ssp. vaseyana were analyzed for secondary metabolic products. Methacrolein, five monterpenes, three sesquiterpene lactones, six coumarins, and one flavonoid were identified in the leaves; the contents of the litter were nearly identical. Soils collected directly beneath the shrubs contained the three sesquiterpene lactones, two coumarins and an unknown flavonoid. The litter and water extracts of the litter inhibited the germination of sagebrush seeds. Soils charged with monoterpenes from sagebrush leaves also inhibited seed germination. In addition, the monoterpene contents from eight sagebrush taxa collected from Western Montana are reported.     

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.     

Anticancer sesquiterpene lactones of Michelia compressa (magnoliaceae)

Investigation of the cytotoxic active components of Michelia compressa afforded two new cytotoxic sesquiterpene lactones, michelenolide and micheliolide. Parthenolide, costunolide, santamarine, reynosin and liriodenine were also isolated and exhibited cytotoxic activity. The known sesquiterpene lactones, lanuginolide and dihydroparthenolide, were isolated but were not active. Two other new inactive sesquiterpene lactones, compressanolide and dihydroreynosin, were also obtained. The structures of michelenolide and micheliolide were confirmed by partial synthesis from parthenolide and the structure of compressanolide by partial synthesis from dihydroparthenolide.     

Chemical variation and defense of Encelia farinosa

Chemical analysis of leaves from 12 different localities of Encelia farinosa (including var. phenicodonta and var. radians) collected on the peninsula of Baja California (Mexico) revealed the presence of various chemotypes that differed with regard to the concentrations of chromenes and sesquiterpene lactones. Localities of E. farinosa collected in the northern part of Baja California were characterized by high concentrations of the chromene encecalin (up to 252 μmol g⁻¹ dry wt.), whereas the sesquiterpene lactone farinosin was not detected. Localities of E. farinosa collected at the southern tip of the peninsula lacked encecalin, but were shown to accumulate farinosin (up to 85 μmol g⁻¹ dry wt.) instead. On the mainland of Mexico, as well as in Arizona (U.S.A.), farinosin concentrations varied from 18 to 44 μmol g⁻¹ dry wt. for 10 different localities analyzed. Chromenes were not detected or present only in minor amounts (up to 13 μmol g⁻¹ dry wt.), when compared to the samples from northern Baja California. Chemical variation within localities was small when compared to variation between different localities. Accumulation of encecalin and aridity seem to coincide at least on the peninsula of Baja California, as localities of E. farinosa that receive the least amount of rainfall contained the largest amounts of encecalin in their leaves. Leaves of E. farinosa that contained sufficiently large amounts of either encecalin or farinosin were both detrimental to neonate larvae of the polyphagous pest insect Spodoptera littoralis as shown by addition of the respective crude leaf extracts to artificial diet. Possible advantages of the observed intraspecific chemical variability of E. farinosa with regard to adaptation by generalist insect herbivores are discussed.     

Systematic implications of sesquiterpene lactones in the subtribe melampodiinae

Within the tribe Heliantheae of the Asteraceae, the genetic boundaries of the subtribe Melampodinae have recently been drastically revised by Stuessy. The number of genera within the subtribe has been reduced and new generic groupings have been established. The present study correlates the distribution of sesquiterpene lactones found in these genera with the newly revised subtribal boundaries. The genera Acanthospermum, Melampodium, Polymnia and Sigesbeckia produce predominantly melampolide-type sequiterpene lactones. Limited chemical data support Stuessy's removal of the genera Desmanthodium, Clibadium and Ichthyothere from the subtribe Melampodiinae. The occurrence of melampolide-type sesquiterpene lactones in members of the genera Tetragonotheca (Helianthinae) and Enhydra (Ecliptinae) indicate a possible position of these genera in the Melampodiinae.     

Variation of sesquiterpene lactone contents in Lactuca altaica natural populations from Armenia

In recent years we initiated extensive studies on the characterization of the population structure of wild Lactuca relatives (WLRs) originating from their center of origin and diversity in Southwest Asia. A comparative phytochemical study of nine sesquiterpene lactones in natural populations of the wild lettuce L. altaica Fisch. & C.A. Mey. (Asteraceae) was performed, based on 22 plants, representing seven original individual seed samples derived from three localities representing three regions in Armenia. The compounds were profiled and quantified in leaves and roots of the plants, grown in a controlled glasshouse. The contents of major sesquiterpene lactones, that including the following eight guaianolides: cichorioside B, lactucin, 11β,13-dihydrolactucin, crepidiaside B, 8-deoxylactucin, jacquinelin, lactucopicrin/11β,13-dihydrolactucopicrin, as well as the germacranolide glucoside – lactuside A, were estimated by HPLC/PDA. The L. altaica plants could be characterized by the occurrence of lactuside A in their roots, and the mixture of lactucopicrin/11β,13-dihydrolactucopicrin in both their roots and leaves by relatively high amounts, similarly to results obtained for three commercial cultivars of L. sativa. The total content of sesquiterpene lactones in the roots was significantly higher than that in the leaves. This study is likely the first report of detailed screening of L. altaica natural populations and individuals, even by low sample size, for any trait. Species within the primary lettuce gene pool, should be considered as an attractive source of germplasm in further research and improvement of cultivated lettuce, Lactuca sativa L. While using interspecific hybridization in order to elevate the sesquiterpene levels in cultivated lettuces, the lactones quality (profile) and quantity, as well as the cross-ability level of the wild Lactuca spp. with the crop and fertility of the obtained offspring should be considered.     

Germacranolides,a guaianolide with a β-lactone ring and further constituents from Grazielia species

An investigation of three Grazielia species afforded, in addition to known compounds, several new sesquiterpene lactones, eight germacranolides, two melampolides and one guaianolide as well as three diterpenes, two geranylgeraniol derivatives and a labda-diene. Three of the sesquiterpene lactones had an additional β-lactone ring, one an acid function, and two others unusual ester functions. The structures were elucidated by spectroscopic methods and some chemical transformations. The chemotaxonomic situation is discussed briefly.     

Terpenoids and bibenzyls of 25 liverwort Frullania species

Twenty-five Frullania species (liverworts) were chemically investigated. Fourteen species produce allergy-inducing sesquiterpene lactones. Eighteen species contain bibenzyls. The sesquiterpene lactones and bibenzyls are obtained as the major components and they are valuable chemosystematic markers of Frullania species. On the basis of their chemical constituents, Frullania species can be divided into five chemotypes: sesquiterpene lactone-bibenzyl type; sesquiterpene lactone type; bibenzyl type; monoterpene type and cyclocolorenone type.     

Three bourbonenolides and other sesquiterpene lactones from two vernonia species

A re-investigation of V. arkansana afforded several new sesquiterpene lactones, three bourbonenolides, obviously closely related to those isolated from this plant previously, a glaucolide and a methoxy derivative most probably formed by fragmentation of the corresponding bourbonenolide. From V. profuga in addition to known lactones a new guaianolide was isolated. The biogenetic relationships of the Vernonia sesquiterpene lactones are discussed briefly.     

Sesquiterpene lactones from Michelia fuscata

Two new sesquiterpene lactones, desacetyllanuginolide and michefuscalide were isolated from Michelia fuscata along with two known lactones, dehydrolanuginolide, lipiferolide and a lignan, syringaresinol. The structures of desacetyllanuginolide and michefuscalide were determined by spectral and chemical methods.     

Sesquiterpene lactones from Brachylaena species

The investigation of two Brachylaena species afforded in addition to known sesquiterpene lactones and other constituents five new lactones, a germacranolide, a guaianolide and three eudesmanolides. The structures were elucidated by spectroscopic methods. The chemotaxonomy of this complex genus is discussed.     

Pungent sesquiterpene lactones of the european liverworts Chiloscyphus polyanthus and Diplophyllum albicans

The characteristic pungency of the European liverwort, Chiloscyphus polyanthus, is due to a mixture of four sesquiterpene lactones, two new structures ent-5β-hydroxydiplophyllin and ent-3-oxodiplophyllin, and the previously known diplophyllin and diplophyllolide. A new dihydrodiplophyllin, together with the pungent diplophyllolide and diplophyllin, has been isolated from Diplophyllum albicans. Ent-dihydrodiplophyllolides derived from the above pungent diplophyllolides produce intense numbness of the tongue. All pungent sesquiterpene lactones showed inhibitory activity towards the germination and root elongation of rice husks.     

Zwei neue sesquiterpenlactone und eine neue sesquiterpensäure aus Helenium puberulum

The reinvestigation of Helenium puberulum afforded in addition to known compounds two new sesquiterpene lactones, desacetyl-isobigelovin and a guaianolide, and an anomalic sesquiterpene hydroxy acid. The structures are elucidated by spectroscopic methods. Chemotaxonomic aspects are discussed briefly.