Alkaloids

Definition
Alkaloids are basic nitrogen containing
compounds. They are generally obtained
from plants, animals and microorganisms
and
often demonstrate a marked physiological
action
ALKALOID DESCRIPTION
 Contains nitrogen -usually derived from an amino acid.

 Bitter tasting, generally white solids (exception -nicotine is a

brown liquid).

 They give a precipitate with heavy metal iodides.

 Caffeine, a purine derivative, does not precipitate like most
alkaloids.

 Alkaloids are basic -they form water soluble salts. Most alkaloids
are well-defined crystalline substances which unite with acids to
form salts. In plants, they may exist
 in the free state,
 as salts or
 as N-oxides.
 Occur in a limited number of plants. Nucleic acid exists in
all plants, whereas, morphine exists in only one plant
TESTS FOR ALKALOIDS
Most alkaloids are precipitated from neutral
or slightly acidic solution by
Dragendorff's reagent (solution of potassium
bismuth iodide)orange coloured precipitate.
Mayer's reagent (potassio mercuric
iodide solution) Cream coloured
precipitate.
Wagner’s reagent (iodine in potassium
iodide) red-brown precipitate
Hagers reagent (picric acid) yellow precipitate
Caffeine does precipitate
OCCURRENCE, DISTRIBUTION& LOCATION OF
ALKALOIDS
Occur in bacteria(Pseudomonas aeruginosa)
and rarely in fungi (pscilocin from hallucinogenic
mushrooms).
Some alkaloids occur in several genera from
different species (caffeine), but most occur in closely
related species.
Some occur in certain families (hyoscyamine),
while others occur only in a specific species
(morphine).
Rarely do plants contain more than 1 type
of alkaloid.
All alkaloids of one plant will have a
common biogenenetic 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
PHYSICAL-CHEMICAL PROPERTIES OF
ALKALOIDS
MW: 100 –900
Most bases which do not contain O2 are liquid at
room temperature (nicotine), while those that do are
solids. In rare cases they are coloured.
Most solid bases rotate the plane of
polarized light, have high melting points.
Normally are not soluble in water
(occasionally slightly soluble).
Soluble in a polar or slightly polar organic
solvents. Soluble in concentrated hydroalcoholic
solutions
The basicity of alkaloids depends on the availability
of the lone pair of e-on the N2 atoms: e-donating
groups enhance basicity, while e-withdrawing groups
decrease it.
Because some alkaloids have a carbonyl group
on the amide, they can also be neutral (colchicine
& piperine).
Basic characteristic renders complex alkaloids
unstable, so that in solution they are sensitive to
heat, light & oxygen.
Basic character of alkaloids also allows them to
form salts with mineral acids (such as
hydrochlorides, nitrates and sulphates) or inorganic
acids (tartrates, sulfamates).
Alkaloid salts are soluble in water and dilute
NAMING OF ALKALOIDS
Numerous methods can be used to name alkaloids
1-Generic plant name –atropine from Atropa belladonna
2-Specific name of the plant –cocaine from
Erythroxylum coca.
3Common name of the herb –ergotamine from ergot
(rye)
4Physiological action of the plant –emetine producing
emesis
5Other –e.g. morphine derived from ancient Greek
mythology –Morpheus –god of dreams
EXTRACTION OF
ALKALOIDS
 Extraction is based on the basicity of alkaloids and on the fact that
they normally occur in plants as salts (i.e.: on the solubility of
bases and salts in water and organic solvents).
 Herbs often contain other materials which can interfere with
extraction such as large amounts of fat, waxes, terpenes, pigments
and other lipophilic substances (e.g by forming emulsions) –avoided
by defatting the crushed herb (using petroleum ether and hexane.
 Extraction method normally depends on the raw material, the
purpose of extraction & the scale on which is to be performed.
 For research purposes: chromatography allows for quick and reliable
results.
 If larger amounts of alkaloids need to be extracted, one of
the following methods can be used.
GENERAL METHOD
• Powdered, defatted herb is mixed
with an alkaline aqueous solution.
• Free bases are then extracted
with organic solvents.
• Normally aqueous ammonia is
used, but a carbonate solution is
used when alkaloids contain
fragile elements such as a ester
or lactone.
• In some cases, e.g. Cinchona
bark, a mixture of calcium
hydroxide & sodium hydroxide
should be used as the alkaloids
are bound to tannins.
• Organic solvent:
chloroform, dichloromethane or
ethyl acetate –depends on the
Step II

Organic solvent containing

alkaloids (bases) is separated from
residue & concentrated by
distillation under pressure if
needed.

Solvent is stirred with an acidic

aqueous solution: alkaloids gomain into the
solution as salts. Impurities rein
the organic phase.
• Aqueous solution of alkaloid
salts is washed with an
apolar solvent (hexane)

• Alkalinized with a base using

an organic solvent not
miscible with water.

• Alkaloids precipitate and

dissolve in the organic
phase.

• Extraction of aqueous phase

continues till all alkaloids have
moved into the organic phase
(tested when Mayer’s
reaction on the aqueous
phase becomes negative).

• This purification step may

be carried out in a
Step III
Organic solvent containing alkaloid bases is
decanted, freed from water traces (drying over
anhydrous salt e.g. sodium sulphate) and
evaporated under reduced pressure.
A dry residue remains: total basic alkaloids.
 Extraction of liquid alkaloids

2 Methods possible
1 Plant powder is extracted directly
with acidified water
2Plant powder is extracted with
acidified alcoholic or a hydroalcoholic
solution. This is then followed by
distillation under vacuum (eliminates
that alcohol, leaving behind and
acidic aqueous solution of alkaloid
salts)
Classification of
Alkaloids
1. Biological origin

Sedatives : Morphine
Vasodilatation : Ephedrine,
Ergonovine
.
Local anesthetic : Cocaine
Hallucinating : Mescaline, Psilocybin.
2-Biosynthetic pathway
Ornithine- Tropane, Pyrrolidine, Pyrrolizidine
Tyrosine-Benzyl isoquinoline
Tryptophane- Indole alkaloids, Quinoline
Pyridine- Pyridine
Lysine- Quinolizidine, Piperidine
3- Chemical classification

 True (Typical) alkaloids that are derived from

amino acids and have nitrogen in a
heterocyclic ring. e.g Atropine
 Proto alkaloids that are derived from amino
acids and do not have nitrogen in a
heterocyclic ring. e.g Ephedrine
 Pseudo alkaloids that are not derived from
amino acids but have nitrogen in a heterocyclic
ring. e.g Caffeine
 False alkaloids are non alkaloids give false
positive reaction with alkaloidal reagents.
A. Proto alkaloids

These are also called Non heterocyclic or

Atypical alkaloids or Biological amines.
These are less commonly found in nature.
These molecules have a nitrogen atom which
is not a part of any ring system.
Examples of these include
ephedrine, colchicine, erythromycin and taxol
etc.
Table below shows the chemical structure and
biological significance of these compounds:
Name Structure Biological
Significance

Adrenergic agent-
Ephedrine us ed for ast hma and
ha y fever

C olchicine Relieves gout

Erythromycin Antibiotic
 Used in the
treatment of ovarian
Taxol cancer, breast
(Paclitaxe cancer and non-
l) small cell lung
cancer
B. Heterocyclic Alkaloids or Typical Alkaloids:
Structurally these have the nitrogen as a part of
a cyclic ring system.
These are more commonly found in nature.
Heterocyclic alkaloids are further subdivided
into 14 groups based on the ring structure
containing the nitrogen
No. Heterocycle Example
Hygrine, Stachydrine
Pyrrole and

Pyrrolidine
1.

Senecionine, Symphitine, Echimidine,

Seneciphylline

Pyrrolizidine

2.
 Lobeline, Nicotine, Piperine, Conine,
Pyridine a nd Piperidine Tr i g o n e l l i n e

3.

Cocaine, Atropine, Hyoscyamine, Hyoscine

Tr o p a n e ( p i p e r i d i n e / N - m e t h y l -
pyrrolidine)

4.

Quinine, Quinidine, Cinchonine,

Cinchonidine

Quinoline

5.
 Morphine, Emetine, Papaverine, Narcotine,
Tubocurarine, Code ine

Isoquinoline

6.

Boldine
Aporphine (reduced
isoquinoline/naphthalene)

7.

Lupanine, Cytisine, Laburnine, Sparteine

Quinolizidine

8.
 Ergometrine, Vinblastine, Vincristine, Strychnine, Brucine,
Ergotamine, Yohim bine, Reserpine, Serpentine,
Phys ostigmine
Indole or
Benzopyrole

9.

Castanospermine, Swainsonine
Indolizidine

10.

Pilocarpine, Pilosine
Imidazole or
glyoxaline

11.
 Caffeine, Th e o b r o m in e

Purine (pyrimidine/imidazole)

12.

Conessine, Solanidine

13. Steroidal (so me c o mb i n e d as

glycosides)*

Aconitine, lycaconitine, Aconine

14. Te r p e n o i d *

*Note- Steroidal and terpenoid classes are also treated as separate classes or along with glycosides.