2. Definition
first mentioned in 1819 by W. Meißner, an apothecary from Halle. He observed
that these compounds appeared “like alkali”, and so named them alkaloids
Alkaloids are low-molecular weight, nitrogenous specialized metabolites
occurring in approximately 20% of plant species.
alkaloids are a special group of chemicals that are active at different cellular
levels of organisms, and they take part in the biological processes of plants,
animals and microorganisms
Many of the about 12,000 structurally elucidated alkaloids show potent
biological activity
3. Alkaloids comprise a variety of
heterocyclic secondary metabolite
Alkaloids belong to a group of secondary metabolites that are synthesized
from amino acids and contain one or several N atoms as constituents of
heterocycles.
Many of these alkaloids act as defense substances against animals and
microorganisms
Since alkaloids usually are bases, they are stored in the protonated form,
mostly in the vacuole, which is acidic.
Since ancient times humans have used alkaloids in the form of plant extracts
as poisons, stimulants, and narcotics, and, last but not least, as medicine.
4. Types of alkaloids
Alkaloids can be classified in the terms of their
(1) biological and ecological activity;
(2) chemical structures and
(3) biosynthetic pathway.
From the point of view of biological activity it is possible to divide alkaloids into
(1) neutral or weakly basic molecules (e.g., lactams such as ricinine, certain N-oxides such as
indicine),
(2) animal-derived alkaloids (e.g., anuran, mammalian and arthropod alkaloids), (3) marine
alkaloids,
(4) moss alkaloids,
(5) fungal and bacterial alkaloids and
(6) non-natural alkaloids (structurally modified or analogues).
5. True alkaloids
True alkaloids derive from amino acid and they share a heterocyclic ring with
nitrogen.
These alkaloids are highly reactive substances with biological activity even in
low doses.
All true alkaloids have a bitter taste and appear as a white solid, with the
exception of nicotine which has a brown liquid.
True alkaloids form water-soluble salts.
Moreover, most of them are well-defined crystalline substances which unite
with acids to form salts.
True alkaloids may occur in plants (1) in the free state, (2) as salts and (3) as
N-oxides.
9. The devil’s-pepper genus
contains l-tryptophan-
derived alkaloids. Rauwolfia
serpentina appears on
flowers
l-tryptophan with its
aromatic side chain is a
precursor of indole,
terpenoid indole, quinoline,
pyrroloindole and ergot
alkaloids.
10. In 1806 the pharmacy assistant Friedrich Wilhelm Sertürner isolated morphine
from poppy seeds.
Another 146 years had to pass before the structure of morphine was finally
resolved in 1952. More than 10,000 alkaloids of very different structures are now
known. Their synthesis pathways are very diverse, to a large extent still not known
11. Figure shows a small selection of important alkaloids. Alkaloids are classified according to their
heterocycles. Coniine, a piperidine alkaloid, is a very potent poison in hemlock. Socrates died
when he was forced to drink this poison
12. Nicotine
Nicotine, which also is very toxic, contains a pyridine and a pyrrolidine ring. It
is formed in the roots of tobacco plants and is carried along with the xylem
sap into the stems and leaves.
Nicotine sulfate, a byproduct of the tobacco industry, is used as a very potent
insecticide (e.g., for fumigating greenhouses). No insect is known to be
resistant to nicotine.
13. Cocaine,the well-known narcotic,contains tropaneas a heterocycle,in which the N atom is a
constituent of two rings.
A further well-known tropane alkaloid is atropine a poison contained in deadly nightshade
(Atropa belladonna).
In low doses, it dilates the pupils of the eye and is therefore used in medicine for eye
examination. Cleopatra allegedly used extracts containing atropine to dilate her pupils to
appear more attractive
14. Quinine,a quinoline alkaloid from the bark of Chinchuna officinalis growing in South America,
was known by the Spanish conquerors to be an antimalarial drug.
The isoquinoline alkaloid morphineis an important painkiller and is also a precursor for the
synthesis of heroin. Caffeine, the stimulant of coffee, contains a purine as the heterocycle.
15. In the search for new medicines, large numbers of plants are being analyzed
for their content of secondary metabolites.
As a result of a systematic search, the alkaloid taxol, isolated from the yew
tree Taxus brevifolia, is now used for cancer treatment.
Derivatives of the alkaloid camptothezine from the Chinese “happy tree”
Camptotheca acuminata are also being clinically tested as cancer
therapeutics. The search for new medicines against malaria and viral
infections continues.
Since large quantities of pharmacologically interesting substances often
cannot be gained from plants, attempts are being made with the aid of
genetic engineering either to increase production by the corresponding plants
or to transfer the plant genes into microorganisms in order to use the latter
for production.
17. three general examples of the synthesis of alkaloids from amino acids:
(1) synthesis of the pyrroline ring and derived alkaloids from ornithine;
(2) synthesis of the piperidine ring and derived alkaloids from lysine and
(3) synthesis of isoquinolizidine alkaloids from tyrosine.
18. There are only four basic active blocks
for the secondary compounds
1. Acetyl coenzyme A (acetyl CoA) is used in the acetate pathway, and
2. shikimic acid in the shikimate pathway.
3. The third block, mevalonic acid, is active in the mevalonate pathway,
4. and the last, 1-deoxyxylulose 5-phosphate, key to the deoxyxylulose
phosphate pathway
19.
20. Alkaloid biosynthesis needs the
substrate
The synthesis of alkaloids starts from the acetate, shikimate, mevalonate and
deoxyxylulose pathways.
The acetyl coenzyme A pathway (acetate pathway) is the source of some
alkaloids and their precursors (e.g., piperidine alkaloids or anthranilic acid as
aromatized CoA ester (antraniloyl-CoA)).
Shikimic acid is a product of the glycolytic and pentose phosphate pathways,
a construction facilitated by parts of phosphoenolpyruvate and erythrose 4-
phosphate.
The shikimic acid pathway is the source of such alkaloids as quinazoline, quinoline
and acridine.
21. The mevalonate pathway is based on mevalonic acid (three molecules of
acetyl-CoA) which is closely related to the acetate pathway, while the
deoxyxylulose phosphate pathway is based on a combination of pyruvic acid
and glyceraldehyde 3-phosphate (both from the glycolytic pathway). Together,
mevalonate and deoxyxylulose phosphate pathways produce terpenoid and
steroid compounds.
22. Nicotiana tabacum
Tobacco (Nicotiana tabacum) is one of those species, and it has become an
economically important crop plant because of alkaloid production, although
the entire Nicotiana genus is recognized for producing these type of
metabolites
The alkaloids found in Nicotiana plants are toxic compounds that play a major
role in defense against generalist herbivores
The root represents the main site of alkaloid synthesis in Nicotiana species
After their production, the alkaloids are transported through the xylem and
accumulated in leaves, which are the areas more susceptible to herbivore
attacks
23. Regarding its ecological importance, alkaloid biosynthesis is a complex
process that involves several enzymatic steps
Nicotine has two ring moieties, a pyrrolidine ring and a pyridine ring, derived
from two branch pathways
The pyridine ring of nicotine is derived from nicotinic acid, whereas the
pyrrolidine ring originates from polyamine putrescine metabolism, which is
gradually modified to N-methylpyrrolinium
24. Nicotine biosynthesis in
a root cortical cell of
Nicotiana.
Nicotine biosynthesis in a root cortical cell of
Nicotiana.
Enzymes are indicated in red letters. AO,
aspartate oxidase; QS, quinolinic acid
synthase; Gly-3-P, glyceraldehyde-3-P; QPT,
quinolinate phosphoribosyltransferase; ADC,
arginine decarboxylase; ODC, ornithine
decarboxylase; AIH, agmatine
iminohydrolase; CPA, N-carbamoylputrescine
amidohydrolase;
PMT, putrescine N methyltransferase; MPO,
N-methylputrescine oxidase; BBL, berberine
bridge enzyme-like; MATE1/2, multidrug and
toxic compound extrusion 1 and 2; NUP1,
nicotine uptake permease 1; ???: undefined
step.
25. Nicotine produced in the Nicotiana root cells is translocated through the xylem to the leaves,
where it can be demethylated to nornicotine. Nornicotine, by the action of an acyltransferase, is
acylated to N-acylnornicotine (NacNN) in the trichomes. NacNN is secreted by the glandular
trichome, and acts in the antiherbivory defense. ER, endoplasmic reticulum.
26. References
Singh A. and D.P. Isabel. 2015. BIOSYNTHESIS OF AMARYLLIDACEAE ALKALOIDS:
A BIOCHEMICAL OUTLOOK. Alkaloids. ISBN: 978-1-63482-074-5
Zenkner et a; BIOSYNTHESIS IN NICOTIANA: A METABOLIC OVERVIEW. Tobacco
Science (2019) 56:1–9.
Hotti.H. and H. Rischer. The killer of Socrates: Coniine and Related Alkaloids
in the Plant Kingdom. Molecules 2017, 22(11),
1962; https://doi.org/10.3390/molecules22111962
Jan et al., 2012. Plant tropane alkaloid biosynthesis evolved independently in
the Solanaceae and Erythroxylaceae. 10304–10309. PNAS. vol. 109 no. 26
