191
12
(inhibitor of the acetylcholine esterase, approved as symptomatic treatment for Alzheimer’s
disease), haemanthamine (an alkylating agent, inducing DNA-damage), or lycorine (poison found, for instance, in daffodil bulbs causing nausea) is synthetized (Jin 2016). Some
of these compounds, for instance, galantamine, have allelopathic functions for the plants.
12.6.2 Phenylethylisoquinoline Alkaloids
Dopamine (from tyrosine) and 4-hydroxydihydrocinnamaldehyde (from phenylalanine)
are condensed in a Mannich-like reaction (see 7 Fig. 9.2d) to a phenylethylisoquinoline
derivative, which gives rise to autumnaline and further to colchicine, which contains an
unusual tropolone ring (Bentley 2001; Larsson and Ronsted 2014). Colchicine is obtained
from the autumn crocus, Colchicum autumnale, and extracts of this plant are used to
alleviate the symptoms of rheumatism and gout. They also have antimitotic activity due
the interaction of colchicine with tubulin, which prevents spindle formation. However, of
natural compounds interacting with microtubule dynamics (like vinblastine and vincristine, see 7 Sect. 12.2) colchicine is not used in chemotherapy because it is too toxic at the
required concentrations.
12.7 Pyridine Alkaloids (e.g. Nicotine), Pyrrolidine Alkaloids (e.g.
Hygrine) and Tropane Alkaloids (e.g. Atropine, Scopolamine
and Cocaine) All Derived from Ornithine and Arginine
Ornithine, a non-protein amino acid, is derived from the urea cycle, by removing urea
from arginine by arginase. Ornithine is as a precursor for tropane alkaloids and one part
of the pyridine alkaloids. It is transformed into putrescine by a decarboxylase. Putrescine
is associated with foul odour. In Nicotiana (tobacco) it was shown that this decarboxylase
cannot only act on ornithine but also on lysine, thereby producing cadaverine, another
compound associated with the odour of decay of dead organisms (7 Sect. 12.10) (Lee and
Cho 2001; Bunsupa et al. 2016). This bifunctional enzyme is localized inside the chloroplast. In contrast, more specific ornithine decarboxylases are localized in the cytosol,
allowing compartmentalization of putrescine and cadaverine in plant cells (Fuell et al.
2010). Putrescine is methylated to N-methylputrescine. This is catalysed by the putrescine N-methyltransferase (PMT) and is the rate-limiting step in this pathway. Oxidative
deamination of N-methylputrescine by the action of a diamine oxidase leads to the
4- methylaminobutanal aldehyde, followed by a spontaneous cyclization that eventually
produces the central intermediate, N-methyl-Δ 1 -pyrrolinium cation.
To form nicotine, the most abundant pyridine alkaloid in tobacco, N-methyl-Δ 1 -
pyrrolium is condensed with 3,6-dihydronicotinic acid (. Fig. 12.5). Therefore, the
structure of nicotine contains a pyridine ring together with a pyrrolidine ring. In plants
3,6-dihydronicotinic acid is derived from aspartatic acid and glycerine-3-phosphate via
quinolinic acid to form nicotinic acid, the pyridine unit (Dewey and Xie 2013; Kajikawa
et al. 2017). Nicotinic acid is an essential component of metabolic coenzymes such as
NAD + and NADP + and has to be taken up with nutrition by animals as vitamin B 3 .
Nicotine acts on animal nicotinic acetylcholine receptors (Green et al. 2013).
Nicotine can be N-demethylated to form nornicotine, which is an undesirable derivative because it constitutes the precursor of the carcinogen N′-nitrosonornicotine. Nicotine
12.7 · Pyridine Alkaloids (e.g. Nicotine), Pyrrolidine Alkaloids (e.g. Hygrine) and....
12
(inhibitor of the acetylcholine esterase, approved as symptomatic treatment for Alzheimer’s
disease), haemanthamine (an alkylating agent, inducing DNA-damage), or lycorine (poison found, for instance, in daffodil bulbs causing nausea) is synthetized (Jin 2016). Some
of these compounds, for instance, galantamine, have allelopathic functions for the plants.
12.6.2 Phenylethylisoquinoline Alkaloids
Dopamine (from tyrosine) and 4-hydroxydihydrocinnamaldehyde (from phenylalanine)
are condensed in a Mannich-like reaction (see 7 Fig. 9.2d) to a phenylethylisoquinoline
derivative, which gives rise to autumnaline and further to colchicine, which contains an
unusual tropolone ring (Bentley 2001; Larsson and Ronsted 2014). Colchicine is obtained
from the autumn crocus, Colchicum autumnale, and extracts of this plant are used to
alleviate the symptoms of rheumatism and gout. They also have antimitotic activity due
the interaction of colchicine with tubulin, which prevents spindle formation. However, of
natural compounds interacting with microtubule dynamics (like vinblastine and vincristine, see 7 Sect. 12.2) colchicine is not used in chemotherapy because it is too toxic at the
required concentrations.
12.7 Pyridine Alkaloids (e.g. Nicotine), Pyrrolidine Alkaloids (e.g.
Hygrine) and Tropane Alkaloids (e.g. Atropine, Scopolamine
and Cocaine) All Derived from Ornithine and Arginine
Ornithine, a non-protein amino acid, is derived from the urea cycle, by removing urea
from arginine by arginase. Ornithine is as a precursor for tropane alkaloids and one part
of the pyridine alkaloids. It is transformed into putrescine by a decarboxylase. Putrescine
is associated with foul odour. In Nicotiana (tobacco) it was shown that this decarboxylase
cannot only act on ornithine but also on lysine, thereby producing cadaverine, another
compound associated with the odour of decay of dead organisms (7 Sect. 12.10) (Lee and
Cho 2001; Bunsupa et al. 2016). This bifunctional enzyme is localized inside the chloroplast. In contrast, more specific ornithine decarboxylases are localized in the cytosol,
allowing compartmentalization of putrescine and cadaverine in plant cells (Fuell et al.
2010). Putrescine is methylated to N-methylputrescine. This is catalysed by the putrescine N-methyltransferase (PMT) and is the rate-limiting step in this pathway. Oxidative
deamination of N-methylputrescine by the action of a diamine oxidase leads to the
4- methylaminobutanal aldehyde, followed by a spontaneous cyclization that eventually
produces the central intermediate, N-methyl-Δ 1 -pyrrolinium cation.
To form nicotine, the most abundant pyridine alkaloid in tobacco, N-methyl-Δ 1 -
pyrrolium is condensed with 3,6-dihydronicotinic acid (. Fig. 12.5). Therefore, the
structure of nicotine contains a pyridine ring together with a pyrrolidine ring. In plants
3,6-dihydronicotinic acid is derived from aspartatic acid and glycerine-3-phosphate via
quinolinic acid to form nicotinic acid, the pyridine unit (Dewey and Xie 2013; Kajikawa
et al. 2017). Nicotinic acid is an essential component of metabolic coenzymes such as
NAD + and NADP + and has to be taken up with nutrition by animals as vitamin B 3 .
Nicotine acts on animal nicotinic acetylcholine receptors (Green et al. 2013).
Nicotine can be N-demethylated to form nornicotine, which is an undesirable derivative because it constitutes the precursor of the carcinogen N′-nitrosonornicotine. Nicotine
12.7 · Pyridine Alkaloids (e.g. Nicotine), Pyrrolidine Alkaloids (e.g. Hygrine) and....