Pyrrolizidine, Quinolizine, and Indolizidine Alkaloids
Pyrrolizidine alkaloids
Pyrrolizidine alkaloids are derived from ornithine or arginine. There are at least 560 of this structural type known. They often occur as N-oxides. Pyrrolizidine alkaloids are synthesized in the roots and transported to other plant parts.
Arginine or ornithine is converted to putrescine. Putrescine is then converted to homospermidine, through an asymmetrical putrescine intermediate. Homospermidine is then incorporated as a symmetrical intermediate into a necine base.
Pyrrolizidine alkaloids usually occur as complex esters of unique monobasic or dibasic acids called necic acids. The ester portion is usually derived from leucine, although acids from isoleucine and other compounds are known.
Distribution
Pyrrolizidine alkaloids are found in the Asteraceae (esp. Senecio) and Eupatorium, Boraginaceae, and Fabaceae Crotalaria. They have been reported from other plants as well.
Toxicity
Most of the toxic effects of pyrrolizidine alkaloids are produced by alkylation of DNA and proteins.
Monocrotaline inhibits Na-K ATPase pumps.
Because the alkaloids are cumulative hepatotoxins and carcinogens, they are often involved in cases of livestock poisoning.
Interactions of pyrrolizidine alkaloids and insects
Pyrrolizidine alkaloids are feeding deterrents and insecticidal for many species of insects. Other insects that feed on the plants, excrete the alkaloids and don't sequester them.
Yet other insects sequester the alkaloids. Two main orders of insects are involved: the Danainae of North America and the Ithomiinae of South America. Both larvae and adults of the Danainae may consume food plants with pyrrolizidine alkaloids, but only adult Ithomiinae are able to obtain the alkaloids. based on metabolized products
Some moths store pyrrolizidine alkaloids without change. Larvae of the cinnabar moth, Tyria jacobea, accumulate these alkaloids and become distasteful to predators. All stages of the moths have warning coloration. Many other insects consume plants with these alkaloids and a number are involved in biological interactions that include the alkaloids.
In addition to the use of pyrrolizidine alkaloids as protective chemicals, species of three groups
of Lepidoptera (Danainae, Ithomiinae, and Arctiidae) biosynthise pheromones from the alkaloids that they
acquire from plants, often during larval feedling. Monarch butterflies, Danaus plexippus, contain
pyrrolizidine alkaloids from larval feeding, but don't appear to use these compounds as pheromones.
Other Danaus species convert ingested pyrrolizidine alkaloids into compounds such as danaidone,
danaidal, and hydroxydanaidal that are released as a component of hairpencil secretions. These compounds
serve as aphrodisiacs and are important in reproduction.
Parasitic plants
The alkaloids of certain Castilleja and Penstemon species contain pyrrolizidine alkaloids derived from host plants that contain the alkaloids. They are transerred from host to parasite. A number of alkaloids that feed on these plants accumulate pyrrolizidine alkaloids.
Medicinal use of pyrrolozidine alkaloids
Many people have been poisoned by using herbal medicines containing pyrrolizidine alkaloids. Some
of these involve Senecio species. Others involve Symphytum spp., comfrey, Boraginaceae.
Although most of these alkaloids are carcinogenic, senecionine and senecionine N-oxide have
antitumor activity.
Quinolizidine alkaloids
Quinolizidine alkaloids are derived from lysine and have two fused 6-membered rings that share a nitrogen. At least 570 are known.
They occur mostly in the subfamily Papilionoideae of the Fabaceae, but have been reported from a number of other families as well. Quinolizidine alkaloids with relatively simple structures are encountered in Lupinus species, whereas complex ones occur in Ormosia (Fabaceae).
Quinolizidine alkaloids occur in the 10 most primitive tribes of the Fabaceae.
Biosynthesis of quinolizidine alkaloids
Quinolizidine alkaloids are derived from lysine via a symmetrical cadaverine intermediate. Despite
some similarities in overall structure to pyrrolizidine alkaloids, quinolizidine alkaloids are derived
by a quite distinctive pathway. Lupanine is not a direct precursor of sparteine. Cytisine and sparteine
are the two most widely distributed quinolizidine alkaloids. These alkaloids are synthesized in
the chloroplasts of mesophyll cells.
Biological activity of quinolizidine alkaloids
Several quinolizidine alkaloids inhibit phenylalanine tRNA binding to ribosomes and interfere with aspects of translation. Anagyrine and cytisine are teratogenic. These alkaloids are often toxic to insects and other animals. However, some insects accumulate them.
Quinolizidine alkaloids are often involved in livestock poisoning.
Alkaloids of this group seldom have bonafide medicinal activity.
Quinolizidine alkaloids and parasitic plants
Quinolizidine alkaloids are often taken up by plant parasites in the genera Castilleja and Penstemon, Scrophulariaceae, much in the same manner that these plants take up pyrrolizidine alkaloids from their hosts.
Species of Cuscuta take up quinolizidine alkaloids from Spartium junceum, Fabaceae.
Hallucinogenic quinolizidine alkaloids
The alkaloids of the mescal bean, Sophora secundiflora, Fabaceae, were used as hallucinogens by American Indians of the Southwest. The main alkaloid in these seeds is cytisine.
Indolizidine alkaloids
This group of alkaloids has a fused 5- and 6-membered ring and is intermediate in that regard to the pyrrolizidine and quinolizidine alkaloids. At least 170 indolizidine alkaloids are known. These alkaloids usually do not react with Dragendorff reagent or with ninhydrin and are usually missed in screening programs.
These alkaloids are found in many different groups of organisms including frogs of the genus Dendrobates and toads of the genus Melanophryniscus. They also are known to occur in Dendrobium, Orchidaceae, species. The two most intensively studied alkaloids of this series are swainsonine and castanospermine. Swainsonine occurs in Swainsona canescens (Australia) and Astragalus and Oxytropus (western U.S.). Castanospermine is best known from the seeds of Castanospermine, Fabaceae, of Australia.
Compounds of this type are largely responsible for the poisoning syndrome known as "locoism" in horses
in the Western U.S.
Biosynthesis of indolizidine alkaloids
Although the overall structures of these alkaloids resemble those of pyrrolizidine and quinolizidine alkaloids, they are very different in biosynthesis.
The biosynthesis of slaframine in Rhizoctonia leguminicola begins with lysine and involves
pipecolic acid as an intermediate. Acetate, via malonate, is responsible for part of the other ring
structure.
Biological activity of indolizidine alkaloids
Castanospermine is a potent inhibitor of almond b-glucosidase, but doesn't inhibit many other glucosidases. This alkaloid also inhibited glycoprotein processing. It also is a potent phytotoxin for plants. Swainsone inhibits one type of a-mannosidases, but was not inhibitory toward others. These compounds promise to be of value for study of the immune response, cancer metastasis, intracellular transport, and viral infectivity. Both castanospermine and swainsonine have been of interest for study of HIV-1.
Other miscellaneous types of indolizidine alkaloids
Several alkaloid types of the family Elaeocarpaceae and of the genus Tylophora, Asclepiadaceae, possess structures with fused 5- and 6-membered rings. They are not closely related to the other indolizidine alkaloids described above, however.
Pyrrolizidine Alkaloid Biosynthesis
Pyrrolizidine Alkaloid Metabolites
Quinolizidine Alkaloid Biosynthesis
Assorted Quinolizidine Alkaloids
Indolizidine Alkaloid Biosynthesis
Lecture Slides
Plants with Pyrrolizidine,
Quinolizidine, and Indolizidine Alkaloids
© David S. Seigler, Plant Biology 363, Plant Secondary Metabolism, Department of Plant Biology,
265 Morrill Hall, 505 S. Goodwin Ave., University of Illinois, Urbana, Illinois 61801, USA.
217-333-7577. seigler@life.uiuc.edu.
