Pyrrolizidine alkaloids (PAs) are heterocyclic secondary metabolites with a typical pyrrolizidine motif predominantly produced by plants as defense chemicals against herbivores. They display a wide structural diversity and occur in a vast number of species with novel structures and occurrences continuously being discovered. These alkaloids exhibit strong hepatotoxic, genotoxic, cytotoxic, tumorigenic, and neurotoxic activities, and thereby pose a serious threat to the health of humans since they are known contaminants of foods including grain, milk, honey, and eggs, as well as plant derived pharmaceuticals and food supplements. Livestock and fodder can be affected due to PA-containing plants on pastures and fields. Despite their importance as toxic contaminants of agricultural products, there is limited knowledge about their biosynthesis. While the intermediates were well defined by feeding experiments, only one enzyme involved in PA biosynthesis has been characterized so far, the homospermidine synthase catalyzing the first committed step in PA biosynthesis. This review gives an overview about structural diversity of PAs, biosynthetic pathways of necine base, and necic acid formation and how PA accumulation is regulated. Furthermore, we discuss their role in plant ecology and their modes of toxicity towards humans and animals. Finally, several examples of PA-producing crop plants are discussed.

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Female gametes of marine brown algae release and/or attract their conspecific males by chemical signals. The majority of these compounds are unsaturated, nonfunctionalized acyclic, and/or alicyclic C11 hydrocarbons. Threshold concentrations for release and attraction are generally observed in the range of 1-1000 pmol. The blends may contain various configurational isomers of the genuine pheromones as well as mixtures of enantiomers. Higher plants produce the C11 hydrocarbons from dodeca-3,6,9-trienoic acid; brown algae exploit the family of icosanoids for biosynthesis of the same compounds. The biosynthetic routes comprise several spontaneously occurring pericyclic reactions such as [3.3]-sigmatropic rearrangements, [1.7]-hydrogen shifts, and electrocyclic ring closures. All pheromones are (a)biotically degraded by ubiquitous oxidative pathways involving singlet oxygen or hydroxyl radicals, which may be produced through the agency of heavy metals, huminic acids, or light.

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Unsaturated C8 and C11 hydrocarbons act as chemical signals (chemotaxis) during sexual reproduction of many marine brown algae. One of these compounds, namely (+)-(6S)-6-(1Z-butenyl)cyclohepta-1,4-diene (= ectocarpene) is also formed as a major hydrocarbon by the flowering plant Senecio isatideus (Asteraceae). On administration of enantiospecifically labelled (8R)- or (8S)-[7,8-2H2]trideca-3,6,9-trienoic acid instead of the natural precursor dodeca-3,6,9-trienoic acid to this plant, the artificial C12 analogue of ectocarpene is formed. Mass spectroscopic analysis of the metabolites revealed this process to be enantiospecific for the C(8)-HRe atom of the precursor acid. The stereochemical course of the overall reaction is in agreement with a precise, U-shaped embedding of the trienoic acid into the active center of the enzyme(s) and Re-attack onto a hydrogen at the C(8) methylene group of this precursor. The reactive intermediate cyclizes by pi-orbital interaction between C(4) and C(6) of the acid and is accompanied by decarboxylation. The first product is a thermally unstable (1S,2R)-cis-1-(1E,3Z-hexadienyl)-2-vinylcyclopropane, which immediately rearranges to (+)-(6S)-ectocarpene (homo-Cope rearrangement). The present work provides first experimental evidence for a homo-Cope rearrangement as a naturally occurring electrocyclic reaction.

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Several cyclic and alicyclic C11 hydrocarbons have been shown to act as gamete releasing and/or attracting pheromones during sexual reproduction of brown algae (Phaeophyceae). The same compounds are also found in the essential oils of various plants, of which the occurrence of the cycloheptadiene-pheromone ectocarpene in Senecio isatideus (Compositae) is noteworthy. Administration of [3H]dodeca-3,6,9-trienoic acid to cuttings of this plant leads to incorporation of radioactivity into ectocarpene. Double-bond-deuterated nona-3,6-dienoic acid is converted to fucoserratene, the pheromone of several Fucales, which is certainly not present among the hydrocarbons of Senecio. This proves that the pool of medium-chain, multiply unsaturated fatty acids includes precursors of all types of highly unsaturated hydrocarbons. Appropriately labelled (deuterium markers) fatty acid homologues were synthesized and applied to Senecio plantlets to unravel the mechanistic aspects. The results strongly suggest radical initiation of the pheromone biosynthesis by abstraction of a single hydrogen from a 1,4-pentadienyl segment of the fatty acid followed by oxidation to the corresponding cation. This causes fragmentation of the reactive intermediate into an olefine and carbon dioxide by neighbouring-group participation of the flanking double bonds. A tentative biosynthetic scheme is deduced from the experimental results which also sets the stereochemistry of the algal pheromones into a uniform mechanistic concept.

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An enzyme catalysing the synthesis of sym-homospermidine from putrescine and NAD+ with concomitant liberation of NH3 was purified 100-fold from Lathyrus sativus (grass pea) seedlings by affinity chromatography on Blue Sepharose. This thiol enzyme had an apparent mol.wt. of 75000 and exhibited Michelis-Menten kinetics with Km 3.0mM for putrescine. The same enzyme activity could also be demonstrated in the crude extracts of sandal (Santalum album) leaves, but with a specific activity 15-fold greater than that in L. sativus seedlings.

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