Comparative Phytochemistry of Polyacetylenes of the Genus <em>Artemisia</em> (Asteraceae): Compounds with High Biological Activities and Chemotaxonomic Significance

As products of the fatty acid biosynthesis polyacetylenes of the genus Artemisia are derived from C18-crepenynic acid as first monoacetylenic precursor. Further desaturation steps, perfomed by desaturase and acetylenase activities, lead to compounds with up to three conjugated triple bonds. Diversification is created by oxidative chain-shortening to C14- or C13-intermediates which are modified to three structural types, representing spiroketal enol ethers, aromatic capillens and isocoumarins, and linear triynes. A fourth group diverges at the diyne-level leading to the dehydrofalcarinol-type. The co-occurrence of dehydrofalcarinols with aromatic acetylenes represents a characteristic biogenetic trend, clearly segregating species of the subgenus Dracunculus. Various aromatic acetylenes characterize samples of A. dracunculus (“tarragon“), showing different trends in accumulating either C12-phenyl-diynes (capillens) or structurally related C13-isocoumarins. The formation of bicyclic spiroketal enol ethers constitutes a prominent chemical character of the subgenera Artemisia and Absinthium, mostly occurring as C14-six-membered ringenol ethers. With the co-existence of C13-five-membered ringenols species of “Absinthia s.l.“ deviate from “Absinthia s.str.“ which are additionally distinguished by an accumulation of sesamin-type lignans. Within the subgenus Artemisia species of the “Abrotana“ differ from the “Vulgares“ group by a preponderance of linear triynes linked with a lack of spiroketals. Their relationship is also underlined by the formation of characteristic sesquiterpene-coumarin ethers. Only a few results are available from the subgenera Seriphidium and Tridentatae, suggesting a general reduction of acetylene accumulation. Biological activities were reported for all four structural types, ranging from antifungal, insecticidal, nematicidal, and cytotoxic properties to allelopathic effects. Of particular interest were their remarkable cytotoxic potencies, under which the very high activity of dehydrofalcarin-3,8-diol may be associated with the high affinity of this type to form extremly stable bonds to proteins acting in signaling pathways. The aromatic acetylene capillin inhibited the viability of various tumor cells in a dose- and time-dependent manner. Its potent apoptosis-inducing activity was induced via the mitochondrial pathway. A group of spiroketal enol ethers was identified as inhibitors of PMA-induced superoxide generation. Among them the epoxide of the isovalerate ester exhibited the highest potency. The ecological impact of acetylene formation became apparent by the allelopathic effects of DME of the linear triyne-type, and the aromatic capillen by inhibiting seed germination and growth of widespread weeds. Based on the present overview most activities can be attributed to derivatives of the dehydrofalcarinol- and aromatic capillen-isocoumarin-type. With respect to the taxonomic problems in classifying the complex genus Artemisia the clear-cut differences in the distribution of four structural types of polyacetylenes significantly contribute to a more natural subgeneric grouping.