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.
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, the N
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 plant’s 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. Mayer’s reagent (potassiomercuric iodide solution)
2. Wagner’s reagent (solution of iodine in potassium iodide)
3. Dragendorff’s reagent (potassium bismuth iodide)
• Alkaloidal coloring reagents:
1. Marqui’s reagent (Formaldehyde-sulfuric acid)
2. Mandalin’s reagent (sulphovanadic acid)
3. Erdmann’s reagent (Nitric acid-sulfuric acid)
Extraction of alkaloids
• There are several methods that can be used for the extraction of
the alkaloids from plant materials. However, the common
procedures are largely based on: (1) the basic nature of most
alkaloids; (2) the subsequent ability to form salts with acids; (3)
the ease by which the free bases can be liberated from their salts
by alkalinization and finally (4) the relative solubility of the
alkaloids and their salts in water and various organic solvents.
• The conventional process involved in the alkaloids separation and isolation
may be divided as follows:
1. Preparation of the sample.
2. Liberation of the free alkaloidal base, by treating the dried material with
suitable alkali.
3. Extraction of the alkaloidal base with an organic solvent.
4. Purification of the alkaloidal extract.
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).
