Pyrrolidine, Tropane, Piperidine and Polyketide Alkaloids
Pyrrolidine alkaloids
About 80 pyrrolidine alkaloids are known. They have 5-membered N-containing rings.
Pyrrolidine alkaloids are derived from ornithine (or arginine in some cases) and lysine with addition of acetate/malonate units. The first steps in the biosynthesis usually are decarboxylation, then oxidation of the resulting amines with diamine oxidases to produce amine-aldehydes that cyclize to form pyrrolidine rings.
Simple pyrrolidine or pyrrolideine units often condense with other compounds to yield additional series of alkaloids. For example, N-pyrrolidine reacts with a derivative of nicotinic acid to form nicotine.
Malonyl-CoA units condense with N-pyrrolideine units to form alkaloids such as hygrine and cuscohygrine.
Putrescine usually from arginine or from ornithine in plants.
The biosynthesis of pyrrolidine alkaloids may involve symmetrical or asymmetrical incorporation of putrescine derived from ornithine or arginine. This usually involves methylation of one of the nitrogens of the putrescine. Incorporation is via a symmetrical intermediate in Nicotiana but via an unsymetrical intermediate in Erythroxylum coca.
Pyrrolidine alkaloids are found in a number of families, but are best known from the Solanaceae,
Convolvulaceae, and Erythroxylaceae.
Tropane alkaloids
In some families, the malonyl-CoA units that form compounds such as hygrine, condense internally to form a bridged structure. These alkaloids, called tropane alkaloids, are best known from the Solanaceae, Convolvulaceae, and Erythroxylaceae, but have been reported from other families. They are known from the Rhizophoraceae.
Differences in labelling patterns have been observed and the stereochemical fate of the original putrescine precursor differs in different plants.
An unsymmetrical putrescine intermediate is incorporated into cocaine in Erythroxylum coca.
Tropinone is a key intermediate in the biosynthesis of many tropane alkaloids in the Solanaceae. Many tropane alkaloids in the Solanaceae occur as esters, especially as tropic acid esters. This somewhat unusual acid is derived from phenylalanine.
Atropine is a mixture of (R and S-hyoscyamine.
Cocaine binds and inhibits the dopamine uptake carrier. This alkaloid currently is a drug of abuse in many countries. It also has been used medicinally as a local anesthetic.
Tropane alkaloid-containing plants have been used medicinally and have folkloric uses in many parts
of the world. Among these are Atropa belladonna, Atropa belladonna, Mandragora
officinalis, Hyoscyamus spp., Duboisia spp., Brugmansia spp. and
Brunfelsia spp. Several tropane alkaloids are hallucinogenic and some are powerful
anticholinergic drugs.
Piperidine alkaloids
At least 700 alkaloids of this structural type are known. They arise from lysine in much the same
manner as pyrrolidine alkaloids are derived from ornithine and arginine. Cadaverine, the diamine
derived from decarboxylation of lysine is usually incorporated as a non-symmetrical intermediate.
Anatabine and anabasine in tobacco are derived in a manner that parallels the origin of nicotine.
On the other hand, ammodendrine in members of the Fabaceae is derived wholly from lysine.
Piperine from Piper nigrum
The pungent compounds in black pepper are piperidine units that have interacted with phenylpropanoid
compounds. The best known of these is piperine.
Piperidine alkaloids with portions derived from malonyl-CoA and phenylalanine
A series of alkaloids similar to pyrrolidine alkaloids arise from combination of malonyl-CoA units with piperideine moieties, to form alkaloids similar to hygrine and cuscohygrine. Best known of these is pseudopelletierine (similar to hygrine, but with a piperidine unit in the molecule). In Lycopodium species, these units are dimerized and converted into a complex series of alkaloids.
Alkaloids in Sedum (Crassulaceae) and Lobelia (Campanulaceae) involve addition of units
from phenylalanine. Lobeline, from Lobelia inflata, Indian tobacco, has been used as a component
of antismoking preparations. Cattle are sometimes poisoned by eating other species of this genus.
Pipecolic acid
Pipecolic acid and a series of alkaloid derivatives appear to be derived from L-lysine, via the
intermediacy of D-lysine.
Coniine and related alkaloids
Alkaloids in the family Apiaceae are uncommon. Coniine, from Conium maculatum, is one of the few encountered. This alkaloid is similar in structure to piperidine alkaloids, but is derived from polyketide pathways. Coniine does, however, occur in several other plants. This alkaloid is highly toxic. Some of these alkaloids also occur in members of the Fabaceae, notably Cassia and Prosopis, and in conifers.
N-Methylpyrrolidine and Related Compounds
Cusocohygrine and Hygrine Formation
Piperine and related alkaloids
Pseudopelletierine Biosynthesis
Polyketide-Derived Piperidine Alkaloids
Lecture Slides
Plants with Pyrrolidine, Tropane,
and Polyketide 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.
