198
12
12.12 Terpenoid Alkaloids (Derived from the MEP Pathway,
e.g. Aconitine)
Terpenoid alkaloids, as the name indicates, originate from the plastidial MEP pathway,
leading to the synthesis of geranyl diphosphate (GPP, see 7 Sect. 10.1 in 7 Chap. 10).
During biosynthesis, a nitrogen atom is added often after cyclization in the form of a
β-aminoethanol, ethylamine, or methylamine. Species of Aconitum (Ranunculaceae,
monkshood, blue rocket) and Delphinium (larkspurs, Ranunculaceae) contain complex
diterpene-derived esters, especially in the roots. Aconitine is a diester of aconine with acetic and benzoic acids. These alkaloids are potent neurotoxins and antiarrhythmic agents
because they block voltage-gated sodium channels (see 7 Chap. 8.1). All species of Aconitum
are potentially toxic to man and animals and must be treated with caution. Another diterpene alkaloid, methyllycaconitine, is also found in many species of Delphinium and has
insecticidal properties. In mammals it has been used to study the nicotinic acetylcholine
receptor (see 7 Sect. 6.2 in 7 Chap. 6).
12.13 Tropane-Related Alkaloids (Derived from Proline,
e.g. Anatoxin A)
Anatoxin A is found in several freshwater cyanobacteria such as Anabaena flos-aquae,
which can occur as an algal bloom. This component acts as a neurotoxin and is an agonist
for the nicotinic acetylcholine receptor. The biosynthesis pathway seems to start from
an activated proline, which is attached to an acyl carrier protein (Mejean et al. 2014).
Prolyl- ACP is oxidized to 1-pyrroline-5-carboxyl-ACP (P5C-ACP) by an oxidase, and
three acetate units are added. Methylation forms the homoanatoxin A precursor.
12.14 Isoxazole Alkaloids (e.g. Muscimol)
Isoxazoles (1,2-oxazole) such as ibotenic acid, muscimol and muscazone are structural
analogues of γ-aminobutyric acid (GABA). They occur in some species of the mushroom
Amanita, especially fly agaric (Amanita muscaria). Muscimol is derived from ibotenic
acid by decarboxylation.
12.15 Muscarine
Muscarine is an agonist for the muscarinic acetylcholine receptor due to its similarity
with acetylcholine and is thought to contribute to the overall psychoactivity of Amanita
muscaria. Its biosynthesis is not yet understood, it is probably derived from pyruvic acid
to yield the tetrahydrofuran-containing quaternary ammonium alkaloid.
12.16 Guanidinium Toxins (e.g. Saxitoxin)
Guanidinium toxins, such as saxitoxin (STX), tetrodotoxin (TTX) and their analogues,
are alkaloids with divergent evolutionary origins but which share the common chemical feature of guanidinium moieties (functional group on the side chain of arginine).
Chapter 12 · Alkaloids
12
12.12 Terpenoid Alkaloids (Derived from the MEP Pathway,
e.g. Aconitine)
Terpenoid alkaloids, as the name indicates, originate from the plastidial MEP pathway,
leading to the synthesis of geranyl diphosphate (GPP, see 7 Sect. 10.1 in 7 Chap. 10).
During biosynthesis, a nitrogen atom is added often after cyclization in the form of a
β-aminoethanol, ethylamine, or methylamine. Species of Aconitum (Ranunculaceae,
monkshood, blue rocket) and Delphinium (larkspurs, Ranunculaceae) contain complex
diterpene-derived esters, especially in the roots. Aconitine is a diester of aconine with acetic and benzoic acids. These alkaloids are potent neurotoxins and antiarrhythmic agents
because they block voltage-gated sodium channels (see 7 Chap. 8.1). All species of Aconitum
are potentially toxic to man and animals and must be treated with caution. Another diterpene alkaloid, methyllycaconitine, is also found in many species of Delphinium and has
insecticidal properties. In mammals it has been used to study the nicotinic acetylcholine
receptor (see 7 Sect. 6.2 in 7 Chap. 6).
12.13 Tropane-Related Alkaloids (Derived from Proline,
e.g. Anatoxin A)
Anatoxin A is found in several freshwater cyanobacteria such as Anabaena flos-aquae,
which can occur as an algal bloom. This component acts as a neurotoxin and is an agonist
for the nicotinic acetylcholine receptor. The biosynthesis pathway seems to start from
an activated proline, which is attached to an acyl carrier protein (Mejean et al. 2014).
Prolyl- ACP is oxidized to 1-pyrroline-5-carboxyl-ACP (P5C-ACP) by an oxidase, and
three acetate units are added. Methylation forms the homoanatoxin A precursor.
12.14 Isoxazole Alkaloids (e.g. Muscimol)
Isoxazoles (1,2-oxazole) such as ibotenic acid, muscimol and muscazone are structural
analogues of γ-aminobutyric acid (GABA). They occur in some species of the mushroom
Amanita, especially fly agaric (Amanita muscaria). Muscimol is derived from ibotenic
acid by decarboxylation.
12.15 Muscarine
Muscarine is an agonist for the muscarinic acetylcholine receptor due to its similarity
with acetylcholine and is thought to contribute to the overall psychoactivity of Amanita
muscaria. Its biosynthesis is not yet understood, it is probably derived from pyruvic acid
to yield the tetrahydrofuran-containing quaternary ammonium alkaloid.
12.16 Guanidinium Toxins (e.g. Saxitoxin)
Guanidinium toxins, such as saxitoxin (STX), tetrodotoxin (TTX) and their analogues,
are alkaloids with divergent evolutionary origins but which share the common chemical feature of guanidinium moieties (functional group on the side chain of arginine).
Chapter 12 · Alkaloids