194
12
N-Methyl-Δ 1 -pyrrolium is also the precursor for the biosynthesis of cocaine
(. Fig. 12.5). The additional carbon atoms required for the synthesis of cocaine are derived
from acetyl-CoA, by addition of two acetyl-CoA units to the N-methyl-Δ 1 -pyrrolinium
cation (Drager 2006). The (S)-enantiomer can cyclize to form the tropane ring system
of cocaine. The tropane ring system undergoes hydrolysis and SAM-dependent methylation. Methylecgonone is reduced via NADPH for the formation of methylecgonine with
the help of the methylecgonone reductase. The benzoyl-CoA required for esterification
of methylecgonine to form the cocaine diester is synthesized from phenylalanine via cinnamic acid, and the enzyme needed is an acyltransferase (Schmidt et al. 2015). Cocaine
is a rare alkaloid restricted to some species of Erythroxylum (Erythroxylaceae). The South
American Erythroxylum coca shrub can have up to 1% dry weight of cocaine in its leaves
and has been cultivated for religious and medicinal purposes for more than 8000 years
(Bieri et al. 2006).
Tropane alkaloid biosynthesis is distributed among different families of the angiosperms, but it seems that it has evolved independently in different lineages. In species of
the Solanaceae, which produce compounds such as hyoscyamine, atropine and scopolamine, the enzyme that is important for the reduction of the keto group in the tropane
ring, the tropitone reductase I, belongs to the short-chain dehydrogenase/reductase family. In Erythroxylum coca, which accumulates mainly cocaine, a protein of the aldo-keto
reductase family carries out this reaction (methylecgonone reductase), which has higher
homologies to the chalcone reductase, an enzyme of flavonoid biosynthesis (Jirschitzka
et al. 2012). Cocaine is also mainly accumulating in young developing leaves and, in contrast to Solanaceae, is not found in roots.
12.8 Pyrrolizidine Alkaloids (Derived from Spermidine
and Putrescine)
Pyrrolizidine alkaloids are formed by the condensation of spermidine and putrescine
(both derived from ornithine) or two putrescines to form homospermidine, leading
to necine (Ober and Kaltenegger 2009). Pyrrolizidine alkaloids are composed of a
necine base present as esters with one or more necic acids. They are produced especially in the families Asteraceae, Boraginaceae, Heliotropiaceae, Apocynaceae and the
Orchidaceae.
Senecionine is produced from retronecine by the addition of two molecules of L-Ile.
Pyrrolizidine alkaloids are found in many species, as a defence mechanism against herbivores, but have been studied mostly in Fabaceae (e.g. Crotalaria), Asteraceae (e.g.
Senecio) and Boraginaceae (e.g. Heliotropium, Symphytum and Cynoglossum). Examples
are the hepatotoxic compounds seneciphylline (from Senecio) and echimidine (from
Echium).
Pyrrolizidine alkaloids accumulate in the plant as polar N-oxides, facilitating their
transport within the phloem from the roots (where they are usually produced) to the
above-ground organs and maintaining them in a non-toxic form. N-oxides are then modified by species-specific enzymes. The N-oxides are changed back to the tertiary amines in
the gut of an herbivore, where they then exhibit their hepatotoxic, genotoxic and carcinogenic potential (Lindigkeit et al. 1997; Ruan et al. 2014).
Chapter 12 · Alkaloids
12
N-Methyl-Δ 1 -pyrrolium is also the precursor for the biosynthesis of cocaine
(. Fig. 12.5). The additional carbon atoms required for the synthesis of cocaine are derived
from acetyl-CoA, by addition of two acetyl-CoA units to the N-methyl-Δ 1 -pyrrolinium
cation (Drager 2006). The (S)-enantiomer can cyclize to form the tropane ring system
of cocaine. The tropane ring system undergoes hydrolysis and SAM-dependent methylation. Methylecgonone is reduced via NADPH for the formation of methylecgonine with
the help of the methylecgonone reductase. The benzoyl-CoA required for esterification
of methylecgonine to form the cocaine diester is synthesized from phenylalanine via cinnamic acid, and the enzyme needed is an acyltransferase (Schmidt et al. 2015). Cocaine
is a rare alkaloid restricted to some species of Erythroxylum (Erythroxylaceae). The South
American Erythroxylum coca shrub can have up to 1% dry weight of cocaine in its leaves
and has been cultivated for religious and medicinal purposes for more than 8000 years
(Bieri et al. 2006).
Tropane alkaloid biosynthesis is distributed among different families of the angiosperms, but it seems that it has evolved independently in different lineages. In species of
the Solanaceae, which produce compounds such as hyoscyamine, atropine and scopolamine, the enzyme that is important for the reduction of the keto group in the tropane
ring, the tropitone reductase I, belongs to the short-chain dehydrogenase/reductase family. In Erythroxylum coca, which accumulates mainly cocaine, a protein of the aldo-keto
reductase family carries out this reaction (methylecgonone reductase), which has higher
homologies to the chalcone reductase, an enzyme of flavonoid biosynthesis (Jirschitzka
et al. 2012). Cocaine is also mainly accumulating in young developing leaves and, in contrast to Solanaceae, is not found in roots.
12.8 Pyrrolizidine Alkaloids (Derived from Spermidine
and Putrescine)
Pyrrolizidine alkaloids are formed by the condensation of spermidine and putrescine
(both derived from ornithine) or two putrescines to form homospermidine, leading
to necine (Ober and Kaltenegger 2009). Pyrrolizidine alkaloids are composed of a
necine base present as esters with one or more necic acids. They are produced especially in the families Asteraceae, Boraginaceae, Heliotropiaceae, Apocynaceae and the
Orchidaceae.
Senecionine is produced from retronecine by the addition of two molecules of L-Ile.
Pyrrolizidine alkaloids are found in many species, as a defence mechanism against herbivores, but have been studied mostly in Fabaceae (e.g. Crotalaria), Asteraceae (e.g.
Senecio) and Boraginaceae (e.g. Heliotropium, Symphytum and Cynoglossum). Examples
are the hepatotoxic compounds seneciphylline (from Senecio) and echimidine (from
Echium).
Pyrrolizidine alkaloids accumulate in the plant as polar N-oxides, facilitating their
transport within the phloem from the roots (where they are usually produced) to the
above-ground organs and maintaining them in a non-toxic form. N-oxides are then modified by species-specific enzymes. The N-oxides are changed back to the tertiary amines in
the gut of an herbivore, where they then exhibit their hepatotoxic, genotoxic and carcinogenic potential (Lindigkeit et al. 1997; Ruan et al. 2014).
Chapter 12 · Alkaloids