186
12
Ingestion of these infected grains causes poisoning in humans and animals by inducing
convulsions and hallucinations (“St. Anthony’s Fire” or “ergotism”). Ergot alkaloids have
been associated with historical events of mass hysteria such as dancing epidemics in the
medieval ages, the plague of Holy Fire (because of the burning sensations in the extremities), the Great Fear at the beginning of the French Revolution and the Salem Witch
Trials. However, scientific evidence for this connection is lacking. These fungi can also
colonize plants such as Convolvulaceae, and this infection is even seed-transmitted. This
way some species belonging to the Convolvulaceae, in particular Ipomoea violacea and
Turbina corymbosa, contain high amounts of ergolines, especially in their seeds. Symbiosis
with poisonous fungi protects the host plant from herbivores, while the fungi benefit from
nutrition provided by the plant.
Ergot alkaloid biosynthesis starts with the prenylation of L-tryptophan by dimethyl
allyl pyrophosphate (DMAPP; an isoprene unit) to yield 4-(γ,γ-dimethylallyl) tryptophan
(DMAT). Intramolecular cyclization over several steps leads to chanoclavine-I, a tetracyclic
ring system. The oxidized form, chanoclavine-I-aldehyde, is the last common precursor
of all classes of ergot alkaloids. In a next step, lysergic acid is formed which, after sequential addition of amino acids such as alanine, proline or phenylalanine, forms ergotamine.
This involves formation of peptide bonds and resembles the non-ribosomal biosynthesis
pathway for peptides with ATP-mediated activation of amino acids by forming of thioester
linkages prior to their transfer to lysergic acid. Simpler derivatives of lysergic acid require
the formation of amides, for example, ergine from Rivea and Ipomoea species. Ergometrine
from Claviceps purpurea is the amide formed of lysergic acid with 2- aminopropanol.
12.3 Benzylisoquinoline Alkaloids (Derived from Tyrosine,
e.g. Morphine and Curare)
Tyrosine forms the basis for the synthesis of berberine and other benzylisoquinoline alkaloids (Liscombe and Facchini 2008; Hagel and Facchini 2013). These alkaloids are most
common among the order Ranunculales, specifically the Papaveraceae, Ranunculaceae,
Berberidaceae and Menispermaceae families. Papaver somniferum (opium poppy) is one
of the most extensively investigated species in this respect (Weid et al. 2004; Ziegler et al.
2009; Beaudoin and Facchini 2014).
Benzylisoquinoline alkaloid biosynthesis begins with two tyrosines: one is converted
into tyramine via decarboxylation and further to dopamine (see 7 Sect. 12.4), whereas the
other one is converted to 4-hydroxyphenylacetaldehyd (. Fig. 12.3). Both fuse in a PictetSpengler- type reaction to render (S)-Norcoclaurine (Luk et al. 2007). Dopamine is the
precursor for the isoquinoline moiety, whereas 4-hydroxyphenylacetaldehyde is incorporated as the benzyl component. (S)-Norcoclaurine is changed into (S)-coclaurine, further
to (S)-N-methylcoclaurine and to the intermediate (S)-reticuline. It is being discussed
whether the methyl groups of reticuline act as protecting groups by reducing the possible
coupling modes available during the oxidative coupling process, and these groups are then
removed towards the end of the synthetic sequence.
(S)-Norcoclaurine, also called higenamine, which is enriched in the fruit of Nandina
domestica (sacred bamboo, Berberidaceae), in the roots of Aconitum sp. (monkshood
or wolf ’s bane, Ranunculaceae), Tinospora crispa (Menispermaceae) and the seeds of
Nelumbo nucifera (lotus, Nelumbonaceae), is used as dietary additive for fat burning but
is on the prohibition list of the World Anti-Doping Agency (Zhang et al. 2017).
Chapter 12 · Alkaloids
12
Ingestion of these infected grains causes poisoning in humans and animals by inducing
convulsions and hallucinations (“St. Anthony’s Fire” or “ergotism”). Ergot alkaloids have
been associated with historical events of mass hysteria such as dancing epidemics in the
medieval ages, the plague of Holy Fire (because of the burning sensations in the extremities), the Great Fear at the beginning of the French Revolution and the Salem Witch
Trials. However, scientific evidence for this connection is lacking. These fungi can also
colonize plants such as Convolvulaceae, and this infection is even seed-transmitted. This
way some species belonging to the Convolvulaceae, in particular Ipomoea violacea and
Turbina corymbosa, contain high amounts of ergolines, especially in their seeds. Symbiosis
with poisonous fungi protects the host plant from herbivores, while the fungi benefit from
nutrition provided by the plant.
Ergot alkaloid biosynthesis starts with the prenylation of L-tryptophan by dimethyl
allyl pyrophosphate (DMAPP; an isoprene unit) to yield 4-(γ,γ-dimethylallyl) tryptophan
(DMAT). Intramolecular cyclization over several steps leads to chanoclavine-I, a tetracyclic
ring system. The oxidized form, chanoclavine-I-aldehyde, is the last common precursor
of all classes of ergot alkaloids. In a next step, lysergic acid is formed which, after sequential addition of amino acids such as alanine, proline or phenylalanine, forms ergotamine.
This involves formation of peptide bonds and resembles the non-ribosomal biosynthesis
pathway for peptides with ATP-mediated activation of amino acids by forming of thioester
linkages prior to their transfer to lysergic acid. Simpler derivatives of lysergic acid require
the formation of amides, for example, ergine from Rivea and Ipomoea species. Ergometrine
from Claviceps purpurea is the amide formed of lysergic acid with 2- aminopropanol.
12.3 Benzylisoquinoline Alkaloids (Derived from Tyrosine,
e.g. Morphine and Curare)
Tyrosine forms the basis for the synthesis of berberine and other benzylisoquinoline alkaloids (Liscombe and Facchini 2008; Hagel and Facchini 2013). These alkaloids are most
common among the order Ranunculales, specifically the Papaveraceae, Ranunculaceae,
Berberidaceae and Menispermaceae families. Papaver somniferum (opium poppy) is one
of the most extensively investigated species in this respect (Weid et al. 2004; Ziegler et al.
2009; Beaudoin and Facchini 2014).
Benzylisoquinoline alkaloid biosynthesis begins with two tyrosines: one is converted
into tyramine via decarboxylation and further to dopamine (see 7 Sect. 12.4), whereas the
other one is converted to 4-hydroxyphenylacetaldehyd (. Fig. 12.3). Both fuse in a PictetSpengler- type reaction to render (S)-Norcoclaurine (Luk et al. 2007). Dopamine is the
precursor for the isoquinoline moiety, whereas 4-hydroxyphenylacetaldehyde is incorporated as the benzyl component. (S)-Norcoclaurine is changed into (S)-coclaurine, further
to (S)-N-methylcoclaurine and to the intermediate (S)-reticuline. It is being discussed
whether the methyl groups of reticuline act as protecting groups by reducing the possible
coupling modes available during the oxidative coupling process, and these groups are then
removed towards the end of the synthetic sequence.
(S)-Norcoclaurine, also called higenamine, which is enriched in the fruit of Nandina
domestica (sacred bamboo, Berberidaceae), in the roots of Aconitum sp. (monkshood
or wolf ’s bane, Ranunculaceae), Tinospora crispa (Menispermaceae) and the seeds of
Nelumbo nucifera (lotus, Nelumbonaceae), is used as dietary additive for fat burning but
is on the prohibition list of the World Anti-Doping Agency (Zhang et al. 2017).
Chapter 12 · Alkaloids