196
12
from caffeine in the human liver by removal of a methyl group, but they are also naturally
occurring in the cacao plant, the leaves of the tea plant and the cola nut and can therefore
be found in tea and chocolate.
12.10 Piperidine Alkaloids (e.g. Lobeline), Quinolizidine
Alkaloids (e.g. Cytisine) and Indolizidine Alkaloids
(All Derived from Lysine)
Mainly three different alkaloid groups can be derived from lysine: The piperidine alkaloids, the quinolizidine alkaloids and the indolizidine alkaloids (Bunsupa et al. 2012;
Bunsupa et al. 2016). While ornithine forms 5-membered pyrrolizidine rings, the extra
methylene group in lysine allows the formation of a 6-membered piperidine ring. The
lysine amino acid is first processed into cadaverine (see above) by a lysine decarboxylase
(which can also act on ornithine, see 7 Sect. 12.7 in 7 Chap. 12).
Piperidine alkaloids are lobeline (present in Asterales), pelletierine (present in
Myrtales, e.g. pomegranate, Punica granatum) and piperine (present in Piperales). To
form these, cadaverine is oxidized by a copper-dependent amine oxidase to yield 5-aminopentanal, which is spontaneously cyclized to a Δ 1 -piperideine Schiff base. Side chains
are either formed by attaching acetic acids or derivatives from cinnamoyl-CoA (from the
shikimate pathway) via a Mannich reaction (see . Fig. 9.2d). These alkaloids are produced
in the chloroplast and protect the plants against herbivorous insects (Bunsupa et al. 2012).
Coniines are similar in structure but seem to have a fatty acid precursor rather than lysine
(see 7 Sect. 13.3.4).
Lobeline can be extracted from the plant and seeds of Lobelia (Campanulaceae). Lobelia
inflata is also called the Indian tobacco or asthma weed. Mainly due to the presence of
lobeline, it acts as a respiratory stimulant and has similar effects as nicotine but weaker.
It is used in the treatment of central nervous system disorders and drug abuse (Dwoskin
and Crooks 2002; Kaniakova et al. 2014). Piperine is known for its pungent taste, especially
derived from the dried unripe fruit of Piper nigrum (black pepper, Piperaceae) and other
Piper species. The stereoisomer of piperine, chavicine, is slowly transformed to piperine
on storage, leading to a loss in pungency. Piperine has been attributed many medicinal
properties, among them that it can influence the activity of metabolic enzymes and transporters, thereby changing the pharmacokinetics of therapeutically drugs and/or increasing their bioavailability (Meghwal and Goswami 2013; Lee et al. 2018).
In Nicotiana, Δ 1 -piperideine can condense with 3,6-dihydronicotinic acid (which is
otherwise a precursor for nicotine, see 7 Sect. 12.7 in 7 Chap. 12, . Fig. 12.5). This leads
to anabasine and anatabine, which have a similar function as nicotine in humans and act
as agonist on nicotinic acetylcholine receptors (Dewey and Xie 2013).
The quinolizidine alkaloids have a bi-heterocyclic nucleus and are formed by fusion
of two lysine derivatives, either cadaverine or ∆ 1 –piperideine, via Mannich reactions (see
. Fig. 9.2d). The bicyclic ring system is closely related to the spermidine-/putrescine- derived
pyrrolizidine system (see 7 Sect. 12.8 in 7 Chap. 12). Tiglyl-CoA, p-coumaroyl-CoA or
feruloyl-CoA can be used to add moieties to the quinolizidine alkaloids (Panter and Keeler
1993; Bunsupa et al. 2012). They are found mainly in the Fabales, many of them in Lupinus,
which accumulates primarily derivatives of lupinine and lupanine. Due to their presence in
the crop sweet lupins, the fruits must be soaked in water to prevent toxicity following ingestion. Another quinolizidine alkaloid is sparteine from broom (Cytisus scoparius, Fabaceae).
Chapter 12 · Alkaloids
12
from caffeine in the human liver by removal of a methyl group, but they are also naturally
occurring in the cacao plant, the leaves of the tea plant and the cola nut and can therefore
be found in tea and chocolate.
12.10 Piperidine Alkaloids (e.g. Lobeline), Quinolizidine
Alkaloids (e.g. Cytisine) and Indolizidine Alkaloids
(All Derived from Lysine)
Mainly three different alkaloid groups can be derived from lysine: The piperidine alkaloids, the quinolizidine alkaloids and the indolizidine alkaloids (Bunsupa et al. 2012;
Bunsupa et al. 2016). While ornithine forms 5-membered pyrrolizidine rings, the extra
methylene group in lysine allows the formation of a 6-membered piperidine ring. The
lysine amino acid is first processed into cadaverine (see above) by a lysine decarboxylase
(which can also act on ornithine, see 7 Sect. 12.7 in 7 Chap. 12).
Piperidine alkaloids are lobeline (present in Asterales), pelletierine (present in
Myrtales, e.g. pomegranate, Punica granatum) and piperine (present in Piperales). To
form these, cadaverine is oxidized by a copper-dependent amine oxidase to yield 5-aminopentanal, which is spontaneously cyclized to a Δ 1 -piperideine Schiff base. Side chains
are either formed by attaching acetic acids or derivatives from cinnamoyl-CoA (from the
shikimate pathway) via a Mannich reaction (see . Fig. 9.2d). These alkaloids are produced
in the chloroplast and protect the plants against herbivorous insects (Bunsupa et al. 2012).
Coniines are similar in structure but seem to have a fatty acid precursor rather than lysine
(see 7 Sect. 13.3.4).
Lobeline can be extracted from the plant and seeds of Lobelia (Campanulaceae). Lobelia
inflata is also called the Indian tobacco or asthma weed. Mainly due to the presence of
lobeline, it acts as a respiratory stimulant and has similar effects as nicotine but weaker.
It is used in the treatment of central nervous system disorders and drug abuse (Dwoskin
and Crooks 2002; Kaniakova et al. 2014). Piperine is known for its pungent taste, especially
derived from the dried unripe fruit of Piper nigrum (black pepper, Piperaceae) and other
Piper species. The stereoisomer of piperine, chavicine, is slowly transformed to piperine
on storage, leading to a loss in pungency. Piperine has been attributed many medicinal
properties, among them that it can influence the activity of metabolic enzymes and transporters, thereby changing the pharmacokinetics of therapeutically drugs and/or increasing their bioavailability (Meghwal and Goswami 2013; Lee et al. 2018).
In Nicotiana, Δ 1 -piperideine can condense with 3,6-dihydronicotinic acid (which is
otherwise a precursor for nicotine, see 7 Sect. 12.7 in 7 Chap. 12, . Fig. 12.5). This leads
to anabasine and anatabine, which have a similar function as nicotine in humans and act
as agonist on nicotinic acetylcholine receptors (Dewey and Xie 2013).
The quinolizidine alkaloids have a bi-heterocyclic nucleus and are formed by fusion
of two lysine derivatives, either cadaverine or ∆ 1 –piperideine, via Mannich reactions (see
. Fig. 9.2d). The bicyclic ring system is closely related to the spermidine-/putrescine- derived
pyrrolizidine system (see 7 Sect. 12.8 in 7 Chap. 12). Tiglyl-CoA, p-coumaroyl-CoA or
feruloyl-CoA can be used to add moieties to the quinolizidine alkaloids (Panter and Keeler
1993; Bunsupa et al. 2012). They are found mainly in the Fabales, many of them in Lupinus,
which accumulates primarily derivatives of lupinine and lupanine. Due to their presence in
the crop sweet lupins, the fruits must be soaked in water to prevent toxicity following ingestion. Another quinolizidine alkaloid is sparteine from broom (Cytisus scoparius, Fabaceae).
Chapter 12 · Alkaloids