1. ALKALOIDS
By
Dr. Rakesh Barik

2. Definition
• Alkaloids, which means alkali-like substances, are
complex, heterocyclic, basic nitrogenous compounds of
plant origin.
• Containing nitrogen inside or outside the
heterocyclic ring, which may or may not be derived
from amino acids.
• Generally possessing a marked physiological action
on man or animals, at lower concentration.
The term “ Alkaloid” was coined by the German chemist,
Meissner.

3. • Functions of alkaloids in plants
1. They may act as protective against insects and herbivores
due to their bitterness and toxicity.
2. They are, in certain cases, the final products of
detoxification in metabolic reactions, therefore considered
as waste products of metabolism.
3. They may provide nitrogen to the plant organs in case of
nitrogen deficiency (source of nitrogen).
4. They, sometimes, act as growth regulators in certain
metabolic systems.
5. They may be utilized as a source of energy in case of
deficiency in carbon dioxide assimilation, especially those
alkaloids containing a sugar moiety.

4. Some alkaloids are extremely poisonous e.g.:
•Ergot alkaloids caused epidemic poisoning in the Middle
Ages in Europe as a result of feeding on rye bread
contaminated with the fungus.
•The extracts of plants containing such alkaloids have
long been used as arrow poisons in hunting and warfare
e.g. curare extract that contains tubocurarine alkaloid.
•Certain were employed in this respect, as a draught for
execution e.g. Socrate’s execution, in ancient Greece, with
hemlock which contains coniine.

5. •At the time of the Roman Empire, Belladonna (the
source of atropine) has been mixed with food with
the purpose of murdering.
•Cleopatra, the queen of Egypt used Egyptian
henbane (Hyoscyamus muticus) that contains
hyoscyamine, for suicidal purpose.
Certain alkaloids are widely used for their
psychotropic effects e.g. caffeine acts as CNS
stimulant and nicotine is responsible of the
psychological and physical dependence of tobacco.
Usage History

6. Nomenclature:
Alkaloids terminate with the suffix-ine, their names
may be derived from the:
Atropine from Atropa.
Cocaine from Coca.
Common name, e.g., Ergotamine from Ergot.
Physiological activity, e.g. Emetine (emetic).
 Genus name e.g.,
 Species name, e.g.,


 Discoverer, e.g., Pelletierine from Pelletier.

7. Prefixes and suffixes:
Prefixes:
"Nor-" designates N-demethylation e.g.
Norpseudoephedrine and Nornicotine.
"Apo-" designates dehydration e.g.Apomorphine.
"Iso-, pseudo-, neo-, and epi-“ indicate different types of isomers.
Nornicotine Nicotine Morphine Apomorphine

8. Suffixes:
N
H
H
H
HO
H
N
R
N
H
H
H
H
HO
R
(-)-Quinine
(-)-Cinchonidine
R = OCH3
R = H
N
(+)-Quinidine
(+)-Cinchonine
R = OCH3
R = H
"-dine" designates isomerism as in the case of the Cinchona
alkaloids, quinidine and cinchonidine are the optical isomers of
quinine and cinchonine, respectively.
Cinchona Alkaloids

9. Classification
Different systems of classification based on:
 The pharmacological action (biological activity)
 The chemical structure (type of nitrogen,
heterocyclic or non-heterocyclic and type of ring
structure)
 The biochemical origin (biosynthetic pathway of
production in the plant)
 The taxonomical origin (plant families rich in
alkaloids)

10. According to Hegnauer’s classification, which is based on both the
type of nitrogen and the biochemical origin, three main types of
alkaloids are distinguished:
•True alkaloids: these are derived from amino acids and have
nitrogen in a heterocyclic ring. Show positive results for the
general chemical tests.
•Protoalkaloids: these are derived from amino acids and have
nitrogen outside the heterocyclic ring. Show positive results for the
general chemical tests.
•Pseudo alkaloids: these are not derived from amino acids but have
nitrogen in a heterocyclic ring. Show negative results for the
general chemical tests.

11. CLASSIFICATION OFALKALOIDS
1) Pharmacological action (Biological activity)
Analgesics e.g. Morphine and Codeine
CNS stimulants e.g. Caffeine and Strychnine
Anti-cancers e.g. Vincristine, Vinblastine andTaxol
Mydriatics e.g. Atropine
Myotics e.g. Pilocarpine
Anti-asthmatics e.g. Ephedrine
Anti-tussives e.g. Codeine
Expectorants e.g. Lobelline
Anti-hypertensives e.g. Reserpine
Smooth muscle relaxants e.g. Atropine and Papaverine
Skeletal muscle relaxants e.g. Tubocurarine
Anthelmintics e.g. Pelletierine
Antiparasitics e.g. Quinine and Emetine

12. 2) Chemical structure
A-types of nitrogen, Heterocyclic or non- heterocyclic
B- according to type of ring structure.
a) Non-Heterocyclic or atypical alkaloids
* Sometimes called Protoalkaloids or Biological
amines e.g. Ephedrine, Colchicine, and Taxol.
* All have exocyclic N-atoms.
b) Heterocyclic or typical alkaloids which sub-
divided into several groups according to their ring
structure.

13. Classification of alkaloids
Chemical classification
A) True alkaloids
Sr. no. Type Structure Examples
1. Pyrroleand
pyrrolidine
N
H
N
H
e.g. Hygrine, coca species
2. Pyiridine and
piperidine
N N
H
e.g.Arecoline, anabasine, lobeline,
conine, trigonelline
3. Pyrrolizdine
N
e.g. Echimidine, senecionine,
seneciphylline
4. Tropane
N
e.g.Atropine, hyoscine, hyoscyamine,
cocaine, pseudopelletirine
5. Quinoline
N
e.g. Quinine, quinidine, cinchonine,
cupreine, camptothecine
6. Isoquinoline
N
e.g.Morphine, codeine, emetine,
cephaline, narcotine, narceine, d-
tubocurarine

14. 7 Indole
N
H
e.g. Erotamine, ergotametriene,
reserpine, vincristine, vinblastine,
strychnine, brucine
8 Imidazole N
N
H
e.g. Pilocrpine, isopilocarpine, pilosine
9 Norlupinane
N
e.g. Cystisine, laburinine
10 Aporphine
(reduced
isoquinoline
napthalene)
N
e.g. Boldine

15. B) PROTOALKALOID
1. Alkyalamine Ephedrine, Pseudoephedrine
H O
N H
C) Pseudoalkaloid
1. Purine
N
N N
HN
e.g. Caffeine, thophylline, theobromine
2. Steroidal e.g. Solanidine, conessine,
protoveratrine
3. Diterpene C20H32 e.g. Aconitine, aconine, hypoaconine

16. 3- Alkaloids are classified according to the amino acid that provides boththe
nitrogen atom and the fundamental portion of the alkaloidskeleton.
Amino acid Alkaloid skeleton
Ornithine Pyrrolidine and tropane alkaloids
Lysine piperidine, quinolizidine, and indolizidine alkaloids
Nicotinic
acid
pyridine alkaloids
Tyrosine phenylethylamines and simple tetrahydroisoquinoline
alkaloids,
Tryptophan simple indole, simple β-carboline,
terpenoid indole, quinoline, pyrroloindole, and ergot
alkaloids
Anthranilic
acid
acts as a precursor to quinazoline, quinolineand
acridine alkaloids
Histidine imidazole derivatives

17. Biosynthetic Classification
In this particular instance the significance solely lies to the precursor from
whichthe alkaloids in question are produced in the plant biosynthetically.
1) Indole alkaloids derived from tryptophan.
2) Piperidine alkaloids derived from lysine.
3) Pyrrolidine alkaloids derived from ornithine.
4) Phenylethylamine alkaloids derived from tyrosine.
5) Imidazole alkaloids derived from histidine.

18. Occurrence, Distribution & Location of
Alkaloids
 Occur in bacteria(Pseudomonas aeruginosa) and rarely in fungi (pscilocin
from hallucinogenic mushrooms).
 Some occur in certain families (hyoscyamine), while others occur only
in a specific species (morphine).
 All alkaloids of one plant will have a common biogenetic origin
 Alkaloids occur in all plant parts, but are usually localized in one organ
(e.g. the bark or seeds).
 Within the plant, [alkaloid] can vary widely from part to part –some parts
may contain no alkaloids.
 Occasionally, different alkaloids also form in different parts of the plant.
 Alkaloid concentrations occur in wide ranges –e.g. Madagascar
periwinkle contains 3g per (anti cancer) alkaloids per ton of leaves.

19.  All Parts e.g.
Datura, Vinca.
 Barks e.g.
Cinchona
 Seeds e.g. Nux
vomica
 Roots e.g.
Aconite
 Fruits e.g. Black
pepper
 Leaves e.g.
Tobacco
 Latex e.g.
Opium
Various Sources

20. Physical properties
• Occurrence: Most alkaloids are crystalline
solids. Some are liquids, eg, Coniine, Nicotine
• Color: The majority of alkaloids are colourless
but some are colored. e.g.: Colchicine and
Berberine are yellow. Sanguinarine is red.
Betanidine is orange.
• Taste: Bitter

21. Solubility:
Both alkaloidal bases and their salts are soluble in
alcohol.
Generally, the bases are soluble in organic solvents and
insoluble in water
Exceptions:
Bases soluble in water: caffeine, ephedrine, codeine,
colchicine, pilocarpine and quaternary ammonium bases.
Bases insoluble or sparingly soluble in certain organic
solvents:
Morphine and psychotrine in ether,
Theobromine and theophylline in benzene.

22. Salts are usually soluble in water and, insoluble or
sparingly soluble in organic solvents.
Exceptions:
Salts insoluble In water:
e.g. quinine monosulphate
Salts soluble in organic solvents:
e.g. Lobeline hydrochlorides
soluble in chloroform.

23. Optical activity:
■Many alkaloids are optically active due to the presence of
one or more asymmetric carbon atom (chiral) in their
molecule.
■Optically active isomers show different
physiological activities.
■Usually, the l (-) isomer is more active than the d (+) isomer. e.g.:
l-ephedrine is 3 times more active than d-ephedrine
l-ergotamine is 3 times more active than d-ergotamine.
Exceptions:
■ d-Tubocurarine is more active than the corresponding l- form.
■ Both quinine (l-form) and its d- isomer quinidine are active.
■ The racemic dl-atropine is physiologically active.

24. Chemical Properties
 Most of the alkaloids are basic in nature, due to the availability of lone pair of
electrons on nitrogen.
 The basic character of the alkaloid compound is enhanced if the adjacent functional
groups are electron releasing.
 The alkaloid turns to be neutral or acidic when the adjacent functional groups are
electron withdrawing like amide group which reduces the availability of the lone pair
of electron.
 Their salt formation with an inorganic acid prevents many a time their
decomposition.
 In the natural form, the alkaloids exist either in Free State, as amine or as salt with
acid or alkaloid N-oxides.
 The alkaloid may contain one or more nitrogen and exist in the form of
• Primary amines R-NH2 e.g. Norephedrine
• Secondary amines R2-NH eg. Ephedrine
Tertiary amines R3-N eg. Atropine
Quaternary ammonium salts R4-N eg. D- ubocurarine

25. Tests for detection and identification
Name of
reagent
Composition Observation
Alkaloidal
precipitants:
1.Mayer's test
2. Wagner's test
3. Hager's test
4.Dragendorff's
test
5. Marmé's test
Potassium-mercuric iodide
Iodine in potassium iodide
Saturated solution of picric acid
Potassium bismuth iodide
Potassium cadmium iodide
Color of precipitate:
Creamy white (positive with
most alkaloids, except caffeine
and dilute ephedrine).
Reddish brown
Yellow
Orange-reddish brown
Yellow precipitate

26. Specific Chemical Tests
Alkaloids Name of
Test
Experiment Observation
Tropane
alkaloids
Quinoline
alkaloids
Vitali Morin Test
Thaleoquin Test
The drug is treated
with fuming nitric
acid followed by
evaporation to
dryness. To the
residue, acetone is
added. Methanolic
potassium hydroxide
solution is then
added.
The drug powder is
added with bromine
water and dilute
ammonia solution.
Violet colour change is
formed.
Emerald green colour
change is observed.

27. Alkaloids Name of
Test
Experiment Observation
Opium alkaloids
(Salts of
Meconic acid)
Purine alkaloids
(Pseudo
alkaloids)
Meconic acid Test
Murexide Test
Opium is dissolved
in water and filtered.
To the filtrate, ferric
chloride solution is
added.
The sample is taken
in a petridish.
Potassium chlorate
and HCl are added
and heated to
dryness. The residue
is exposed to dilute
ammonia vapours.
Dark reddish purple
color is formed which
persists on addition of
HCl.
Purple colour is
observed which is lost
upon addition of alkali
solution.