ALKALOIDS

Alkaloids
Definition: the term alkaloid (alkali-like) is commonly used
to designate basic heterocyclic nitrogenous compounds of plant
origin that are physiologically active.
Derived from amino acids.

DEVIATION FROM DEFINITION:

Basicity: Some alkaloids are not basic e.g. Colchicine,
Piperine, Quaternary alkaloids.
Nitrogen: The nitrogen in some alkaloids is not in a
heterocyclic ring e.g. Ephedrine, Colchicine, Mescaline.
Plant Origin: Some alkaloids are derived from Bacteria,
Fungi, Insects, Frogs, Animals.
Biosynthesis: Some alkaloids are not derived from amino
acids e.g purine, steroidal alkaloid .

QUALITATIVE CHEMICAL TESTS FOR ALKALOIDS

General tests answered by all alkaloids are as follows:
1. Dragendorffs test: To 23 mL of the alkaloid solution add few drops of
Dragendorffs reagent (potassium bismuth iodide solution). An orange brown
precipitate is formed.
2. Mayers test: To 23 mL of the alkaloid solution add few drops of Mayers
reagent (potassium mercuric iodide solution). White brown precipitate is
formed.
3. Hagers test: To 23 mL of the alkaloid solution add few drops of Hagers
reagent (saturated solution of picric acid). Yellow precipitate is formed.
4. Wagners test: To 23 mL of the alkaloid solution add few drops of Wagners
reagent (iodine potassium iodide solution). Reddish brown precipitate is
formed.

Physical Properties:
I- State:

Most alkaloids are crystalline solids.

Few alkaloids are amorphous solids e.g. emetine.

Some are liquids that are either:

Volatile e.g. nicotine and coniine, or
Non-volatile e.g. pilocarpine and hyoscine.

II- Color:
The majority of alkaloids are colorless but some are colored e.g.:

Colchicine and berberine are yellow.

betanidine is orange.

The salts of sanguinarine are copper-red.

III- 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
in ether, theobromine and theophylline in benzene.

Salts are usually soluble in water and, insoluble or sparingly soluble in organic
solvents.
Exceptions:
Salts insoluble in water: quinine monosulphate.
Salts soluble in organic solvents: lobeline and apoatropine hydrochlorides are
soluble in chloroform

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

e.g. Ephedrine

Tertiary amines

R3-N

e.g. Atropine

Quaternary ammonium salts R4-N e.g

d-Tubocurarine

Biosynthetic classification
1. Ornithine derived alkaloids
e.g. Pyrrolidine alkaloid-nicotine
Tropane alkaloid Atropine, hyosyamine, coacaine
2. Lysine derived alkaloids
e.g. Piperidine and pyridine alkaloid conine, lobaline, arecoline
Quinazolidine alkaloid- lupinine
3. Tyrosine derived alkaloids
e.g. Isoquinoline alkaloid morphine, codeine, emetine, cephaline, berberine, d- tubocurine
Amino alkaloid- colchicine
4. Tryptophan derived alkaloids
e.g. Indole alkaloid- ergot alkaloid, vincristine, vinblastine, reserpine, strychnine,
physostigmine, strychinine, brucine
Quinoline alkaloid cinchonine, quinine, quinidine, camptothecin
5. Histidine derived alkaloids
e.g. Imidazole alkaloid Pilocrpine
6. Phenylalanine derived alkaloids
e.g. Amino alkaloid- Ephedrine

General reactions for biosynthesis of alkaloids

Some of the general reactions that are of particular

importance

include:

decarboxylation

(removal

of

carboxyl group or carbon dioxide) and transamination

(transfer of an amino group from one molecule to
another without

the formation of ammonia) of the

amino

yield

acids

to

corresponding

amine

or

aldehyde.
These can react to form a Schiff base which, in turn can

react with carbanion in a Mannich-type condensation.

Alkaloid formation may require the involvement

of only one molecule of amino acid, or 2
molecules of the same AA, or less commonly, 2
molecules of different AA or else several
molecules of the same AA.

General reaction

ORNITHINE DERIVED ALKALOIDS

It includes:

Tropane alkaloids

Pyrrolidine alkaloids`

TROPANE ALKALOIDS
(ATROPINE, HYOCYAMINE, HYOSINE, SCOPOLAMINE)

B.S: Atropa belladona (deadly nightshade), Datura

stramonium( thornapple), Hyosyamus niger(henbane).
Family: solanaceae
Part used: dried leaves and flowering tops
Uses: 1.Atropine is classified as anti cholinergic drugs.
Atropine can also be used in SLUDGE syndrome( salivation,
lacrimation, urination, diaphoresis, GIT motility and emesis)
caused by organophosphate poisoning.
Hyoscine is used as antispasmodic.

TRYPTOPHAN DERIVED ALKALOIDS

These include
INDOLE ALKALOIDS
QUINOLINE ALKALOIDS

QUINOLINE ALKALOIDS
The alkaloids containing essentially the quinoline nucleus
include a series of alkaloids obtained exclusively from
the cinchona bark, the major members of this particular group
are, namely: quinine, quinidine, cinchonine and cinchonidine.
Basic Structures

Properties
Quinine is very slightly soluble in H2O, soluble in ethanol,
chloroform, ether, benzene and other organic solvents.
Quinine is a diacidic base. It forms 2 types of sulfates:
Quinine sulfate (neutral and H2O insoluble).
Quinine bisulfate (acidic and H2O soluble).
Quinine (l-isomer) gives quinidine (d-isomer) among other
products when warmed with KOH in amyl alcohol.
Quinine is levorotatory, while quinidine is dextrorotatory.
Tartrates of Quinine and Cinchonidine are insoluble, whereas
the tartrates of Cinchonine and Quinidine are soluble in water.

Tests for identification

1- Fluorescence test:
Solution of the alkaloid in oxygenated acids (e.g H 2SO4, HNO3 or
phosphoric acid) blue fluorescence (+ ve with quinine and quinidine).
2- Thalleoquine test:
Aqueous solution of the alkaloidal salt + Br 2 /H2O (few drops till the
appearance of yellow color) + NH4OH emerald green color
(+ ve with quinine and quinidine).
3- Rosequin test (Erythroquinine test):
Aqueous solution of the alkaloidal salt + dil HCl + Br 2 /H2O (few drops till
the
appearance of yellow color) + CHCl 3 + pot. Ferrocyanide +
NH4OH
red color in the CHCl3 layer (+ ve with quinine and quinidine).

Uses
Quinine is used mainly as anti-malarial in a dose of 2g of
quinine sulfate or other salt for 14 days.
Quinidine is used as a cardiac depressant (antiarrhythmic), particularly to inhibit auricular fibrillation in
a dose of 0.6-1.6 g of quinidine sulfate daily.
Cinchonine and cinchonidine are used as antiinflammatory.
Quinine is used as a flavor in carbonated beverages.

Indole alkaloids
Physostigma alkaloids

Botanical source. Physostigma

venonosum
Common name: calabar bean
Family : Leguminosae
Part used: dried ripe seeds
Main constituents: physostigmine ,
isophysostigmine, physovenine.
Uses: These are the cholinesterase
inhibitors and used as antidote for
atropine poisoning.
Also used to treat glaucoma.

Vinca alkaloids
B.S: Catharanthus roseus
Common name: periwinkle
Family: Apocynacea
Part used: whole plant
Constituents: Vincristine, Vinblastine
Uses: these alkaloids have anticancer
properties.

Ergot alkaoids
B.S: Claviceps purpurea
Family: Hypocreales
Part used: Dried sclerotium of the
fungus
Main constituents: Ergotamine,
Ergometrine, Ergocristine
Uses: Ergotamine is used to treat
migraine and clustur headache.
Ergometrine acts as oxytocic
agent and also used in post-partal
haemorrhage.
Rauwolfia alkaloids
B.S: Rauwolfia serpentina
Common name: indian
snakeroot
Family: Apocyanacea
Part used: leaves
Constituents: serpentine,
reserpine, ajmaline, ajmalacine,
Uses: used as antihypertensive
and antiarrhythmic agent.

Biosynthesis of Vinca alkaloids

Ergot alkaloids

Quinoline alkaloids
B.S: Cinchona Succirubra, C.
calisaya, C. officinalis
Common name; Quina
Family: Rubiaceae
Part used: Dried Bark
Constituents: Quinine, quinidine,
cinchonine, cinchonidine.
Uses: Quinine is a classical
antimalarial.
Quinidine is used for cardiac
arrythmias and atrial fabrillation.

ALKALOIDS DERIVED FROM

TYROSINE

Isoquinoline alkaloids
papaver alkaloids
cephaelis alkaloids

Papaver alkaloids Cephaelis alkaloids

B.S: Papaver somniferum

Family: papaveraceae
Part used: dried milky latex of
poppy capsule.
constituents: Morphine,
codiene, thebaine, Norcotine,
Narciene, papaverine
Uses: Morphine is used as
analgesic.
codiene is used in cough
preparations.

B.S: C.ipecacuanha
Common name: Ipecac
Part used: roots and rhizome
Family: Rubiaceae
Constituents: cephaline, psychotrine,
Emetine,
Uses: ipecacuanha is used as expectorant
and emetic and in the treatment of
Ameobic dysentry.

Emetine

BIOSYNTHESIS OF OPIUM
ALKALOIDS:
------- L-Dopa ------ Dopamine

+
3,4 dipydroxyphenylpyruvic acid
PAPAVERINE ----------------( ket intermediate)
Reticuline
Saluteridine

Saluteredinol

norlaudanosoline

Alkaloids derived from

phenylalanine
EPHEDRINE,
PSEUDOEPHEDRINE

:-

B.S It consists of dried young stem of

Ephedra gerardiana and Ephedra
nebrodensis.
SynonymMa-huang).
Family:- Ephedraceae
C.C:-- It contains the amino alkaloids :
Ephedrine, nor-ephedrine, n-methyl
ephedrine, pseudo-ephedrine.
Uses: it is used in Asthma, hay fever,
flu, cold medications.

Biosynthesis of Ephedrine

END