Alkaloids

A precise definition of the term 'alkaloid' (alkali-

like) is somewhat difficult because there is no clear-
cut boundary between alkaloids and naturally
occurring complex amines.
Typical alkaloids are derived from plant sources,
they are basic, they contain one or more nitrogen
atoms (usually in a heterocyclic ring) and they
usually have a marked physiological action on man
or other animals.
The name 'proto-alkaloid' or 'amino-alkaloid' is
sometimes applied to compounds such as
hordenine, ephedrine and colchicine which lack
one or more of the properties of typical alkaloids.
 Types of Alkaloids
TRUE ALKALOIDS PROTOALKALOIDS PSEUDOALKALOIDS

Derived from Derived from NOT derived from

amino acids simple amines amino acids
Basic in Nature Basic in Nature Very weak basicity

N atom in N atom not in N atom in

heterocyclic ring heterocyclic ring heterocyclic ring or
not
e.g. Atropine, e.g. Mescaline, e.g. Caffeine
Morphine Ephedrine
Physico-chemical properties
Most alkaloids are well-defined crystalline
substances which unite with acids to form salts.
In the plant they may exist in the free state, as salts
or as N-oxides.
In addition to the elements carbon, hydrogen and
nitrogen, most alkaloids contain oxygen.
A few, such as coniine from hemlock and nicotine
from tobacco, are oxygen-free and are liquids.
Although colored alkaloids are relatively rare,
berberine, for example, is yellow and the salts of
sanguinarine are copper-red.
 As a general rule, alkaloids as bases are not soluble
or are sparingly soluble in water, soluble in apolar
or only slightly polar organic solvents, and are
soluble in concentrated hydroalcoholic solutions.

The basicity of alkaloids varies greatly, since this

property depends entirely on the availability of the
lone pair of electrons on the nitrogen atom:
1. Electron-withdrawing groups in close proximity to
the nitrogen atom decrease the basicity, whereas
2. Electron-donating groups enhance the basicity.
 The basic character of the heterocyclic
ring itself varies:
N
Pyridine

in the molecule of pyridine, with 6

electrons, and in the case of quinoline
and isoquinoline, the lone pair of N
Quinoline
electrons on the nitrogen atom is
available and the basicity is clear.

Isoquinoline
 In the case of pyrrole or indole, N
the lone pair of electrons on the
nitrogen atom plays a role in the H
Pyrrole
aromatic character, and the
compounds are not basic (they
are acidic).
N

Indole
Another example is pyrrolidine, H

which is saturated, and is a

strong base.
N

H
Pyrrolidine
Structure and classification

Generally, there are two broad divisions:

1. Heterocyclic or typical alkaloids, divided
into 14 groups according to their ring
structure.
2. Nonheterocyclic or atypical alkaloids,
sometimes called protoalkaloids.
Alkaloids are usually classified according to the
nature of the basic chemical structures from
which they derive.
Nomenclature
The name of all alkaloids should end with
the suffix -ine.
The names of the alkaloids are obtained in
various ways:
1. From the generic name of the plant yielding them, e.g.
atropine.
2. From the specific name of the plant yielding them, e.g.
cocaine.
3. From the common name of the drug yielding them, e.g.
ergotamine.
4. From their physiologic activity, e.g. emetine.
5. From the discoverer, e.g. pelletierine.
Functions of alkaloids in plants

There are several speculations about the

advantages of their presence in plants,
including:
1. Poisonous agents protecting the plant against
insects and herbivores Animals that feed chiefly on plants.
2. End products of detoxification reactions.
3. Regulatory growth factors.
4. Reserve substances capable of supplying nitrogen
or other elements necessary to the plants economy.
Biosynthetic origin

Alkaloids are formed from amino acids, but

other precursors, e.g. terpenes or steroids, are
often also built into the final alkaloidal skeleton.
The amino acids that most often serve as
alkaloidal precursors include:
phenylalanine, tyrosine, tryptophan, histidine,
anthranilic acid, lysine and ornithine.
Tests for alkaloids
There are several general reagents, which may be used to
test the presence of alkaloids or to help their identification.
This includes the alkaloidal precipitating reagents and the
alkaloidal coloring reagents. In addition, there are some
special reagent that can be used for recognizing and
confirming the identity of each alkaloid.
Alkaloidal precipitating reagents:
1. Mayers reagent (potassiomercuric iodide solution)
2. Wagners reagent (solution of iodine in potassium iodide)
3. Dragendorffs reagent (potassium bismuth iodide)
Alkaloidal coloring reagents:
1. Marquis reagent (Formaldehyde-sulfuric acid)
2. Mandalins reagent (sulphovanadic acid)
3. Erdmanns reagent (Nitric acid-sulfuric acid)
 Extraction of alkaloids
Powdered drug
The conventional process
Defatted with Petroleum
involved in the alkaloids ether if necessary
separation and isolation may
Defatted powdered drug
be divided as follows:
1. Preparation of the sample. Moistened render alkaline
with Na2CO3, NH3
2. Liberation of the free
Alkaloids are freed as base
alkaloidal base, by treating the
dried material with suitable Exhaust with Chloroform
alkali.
Total extract
3. Extraction of the alkaloidal
base with an organic solvent. Residual organic fraction Aqueous acid solution
4. Purification of the alkaloidal
Organic solution of
extract. alkaloids bases
Residual aqueous fraction

Crude alkaloid mixture

Pharmacological activity and uses
Alkaloids are particularly interesting substances because
of their multiple pharmacological activities:
1. on the CNS, whether they are depressants (morphine) or
stimulants (caffeine);
2. on the autonomic nervous system: sympathomimetics
(ephedrine) or sympatholytics (yohimbine, certain ergot
alkaloids), parasympathomimetic (pilocarpine), anticholinergics
(atropine, hyoscyamine), or ganglioplegics (nicotine).
In addition, alkaloids include local anesthetics
(cocaine), agents to treat fibrillation (quinidine),
antitumor agents (vinblastine), antimalarials
(quinine), antibacterials (berberine), and amebicides
(emetine).
 Indole Alkaloids
The indole system can be considered to consist of a
pyrrole ring and a benzene ring fused together to form
two isomeric benzopyrroles, INDOLE and ISOINDOLE

The indole alkaloids can be divided into two main classes:

The first class is that of the simple indole alkaloids and the
indole alkaloids of the second class contain two structure-
elements: tryptamine with the indole nucleus and a C9 or C10
- monoterpene moiety, derived from secologanin.
 Indole Alkaloids

The main divisions of the indole alkaloids can be found in:

 Ergot
Synonym: Ergot of rye, Ergota
Biological Source: Ergot is the dried sclerotium of a fungus
Claviceps purpurea Tulasne (Clavicipitaceae or Hypocreaceae)
developed in ovary of rye plant, Secale cereale Linn
(Graminae)
Geographical Source: Switzerland, Yugoslavia, Hungary,
Czechoslovakia.

History: The name of drug is originated from French word

Argot which means fur indicates attachment of sclerotia to rye
like fur attached to body of bird.

Sixteenth century in Germany observed toxic Symptoms

of Ergot like gangrene in extremities and convulsion and called
as St. Antonys fire. In 1836, it was introduced in London
Pharmacopoeia. The life history of fungus first studied by
Tulasne in 1853
 Production of Ergot
By natural way rye plant is host and Claviceps is parasite.
In Life cycle of ergot sclerotial stage or a dormant stage
contains maximum amount of drug.
Ovary of rye plant get infected by ascospores, spreading
influenced by wind and insect.
In favorable conditions (moisture, damp climate)
germination of ascospores leads to hyphal strands.
Hyphae form a white mass of tissue over the surface of
the ovary which is called mycelium (sugary fluid also
called honey dew)
At a same time, hyphal strands produce asexual spores
called conidiospores remain suspended in honey dew
Development stage is the sexual stage and called as
Sphacelial stage
 Hyphae further attack into deeper part of ovary and
slowly replace the entire tissue of ovary called pseudo
parenchyma which is hard and dark purple (sclerotium
stage).
Uncollected sclerotium falls on ground, in favorable
seasons gives out stromata
Each stromatum has globular head and stalk, head
contain large number of perithecia containing sacs of
Ascospores.
Macroscopic Characters:
Colour: Externally dark violet to black, internally pink

Odour: Disagreeable and faint

Taste: Unpleasant

Size: Sclerotia 1- 3 cm in length,

1- 5 mm in width

Shape: Fusiform, triangular,

tapering on both end

Fracture: Brittle with shorth fracture

Chemical Constituents:
Large number of potent indole alkaloids (0.1 to 0.25%)
Derivatives of Lysergic acid present in peptide form hence
called as peptide alkaloids.
 Chemical tests:
1.

+ p dimethyl aminobenzaldehyde
(Van-Urks reagent) Blue
Colour

2.
Ergot+ Solvent ether + H2So4 Filtrate + Na2CO3
Red-
Violet
Colour
3.
Ergometrine + Water Blue Fluorescence