ALKALOIDS

By
Prof. Yahia Elimam
1. Definition:
A precise definition of the term alkaloid
(alkali- like compounds ) is some what difficult
because there is no clear-cut bounderies
between alkaloids and naturally occurring
complex amines .
1.1. Typical alkaloids :
A compound is defined as a typical
(true) alkaloid if it is :
1-
Basic .
2- Contain nitrogen in heterocyclic
ring .
3 - Synthesize in the plant from amino
acids or their immediate derivatives .
4 - Has a marked physiological action .
5 - In most cases, of limited distribution
in the plant kingdom.
1.2. Proto- alkaloids :
These are compounds which
lack one or more of the properties of typical
alkaloids e.g. ephedrine (N- not heterocyclic)
trigonelline (not basic) .
1.3. Pseudo – alkaloids :
These are compounds that are not
synthesized from amino acids or their
immediate derivatives e.g. steroidal alkaloids
synthesized from carbohydrate intermediates
.
2. Occurrence and distribution:
* Alkaloids – bearing plants have been found in
every habitat in which vascular plant grow i.e.
there is no geographical limitations.
* The major source of alkaloids are the
flowering plants , but they have been
discovered in animals , fungi and marine
plants .
* Alkaloids occur in plants in the form of:
a) Salts of acetic, malic ,oxalic ,tartaric , tannic
or other plant acids ( usual form ) .
b) They may also occur in the free state form
(free bases).
c) They may also occur as alkaloid N-oxides.
*Alkaloids have been found in all plant
organs
3. Physical properties:
3.1. Condition :
In the pure state , most of the alkaloids
and their salts are crystalline solids , a few
of the bases are oily liquids e.g. nicotine
and few others are amorphous e.g
emetine.
 3.2. Colour , odour and taste:
Alkaloids are usually colourless, odourless
but have bitter tastes .
*Some alkaloids are coloured e.g. colchicine
is yellow .
 3.3. Solubility :
* Knowledge of the solubility of alkaloids and
their salts is of considerable importance
because
1. Alkaloidal substances are often administered
in solution .
2. The differences in solubility between
alkaloids and their salts are used as a
base for their isolation and purification
from non-alkaloidal substances
3.3.1. The free alkaloid bases are sparingly soluble
in water but soluble in organic solvents
(exceptions morphine and colchicine insoluble in
ether, caffeine base readily soluble in water).
3.3.2. Alkaloid salts are generally soluble in
water less in alcohol and nearly insoluble in
organic solvents (exceptions . apoatropine
hydrochloride and lobeline hydrochloride
dissolve in chloroform.)
• Salts of weak bases are easily decomposed in
solution without alkalinization and release
the bases, which are extracted with organic
solvents.
– Both alkaloidal bases and their salts are
soluble in alchol.
3.3.3. Alkaloid N- oxides are soluble in polar
solvents e.g. water.
3.4. Optical activity :
* Many alkaloids are optically active due to the
presence of one or more asymmetric carbon
atom(s) in their molecules.
* Optically active isomers show different
physiological activities. Usually the l (-) isomer
is more active that the d(+) isomer, however,
there are some exceptions e.g.
i. d- Tubocurarine is more active than the l- form.

ii. Both quinine (l-form) and its d-isomer

quinidine are active .
iii. The racemic dl-atropine is active .
4. Chemical properties:
4.1. Basicity :
The alkaloids are basic (alkaline) in reaction,
due to the presence of a lone pair of electrons
on the amino nitrogen atom(s)
Therefore, they form salts with various acids.
All alkaloids do not have the same degree of
basicity.
• The factors that may influence the degree
of basicity are :
4.1.1. The influence exerted on the electronic
disposition of the nitrogen in the alkaloid
molecule by side chains and various
substitutions .
a) Electron releasing groups, such as alkyl
group , increase the basicity.
 b) Electron withdrawing groups , such as the
carbonyl group, decrease the basicity .
4.1.2. Whether a given alkaloid contains
primary , secondary ,tertiary or quaternary
nitrogen atom(s).
4.1.3. The degree of unsaturation of the
heterocyclic ring .
Unsaturation decreases the basicity .
*The weaker bases would require a more acidic
medium to form salts than would the strongly
basic alkaloids.
* Therefore ,in a medium of a weakly acidic
pH , some strongly basic alkaloids may be
converted to their salt form, while the weaker
 4.2. Stability :
4.2.1. Effect of heat :
Many alkaloids undergo decomposition or
degradation when allowed to stand at
temperature above 70 ° C for long periods of
times .
* In general, alkaloids are less stable in :
i- Solution than in the dry state .
ii- Free base form than in salt form .
• Most tertiary amine alkaloids are easily
transformed to their N- oxides form when
exposed to light and oxygen at elevated
temp.
• N-oxides are :
1. Usually water soluble
2. Characterized by their delayed release properties
3. Low toxicity and low addictive properties

(as compared to parent tertiary alkaloids).

4.2.2. Effect of acids :
Hot dilute acids and concentrated mineral acids
may cause :
1. Dehydration to produce anhydro- or apo-
alkaloids e.g. apomorphine and apoatropine .
2. Elimination of methoxy groups e.g.
conversion of codeine to morphine.
4.2.3. Effect of alkalis :
*Weak alkalis (ammonia) liberate most
alkaloids from their salts .
*Strong alkalis such as NaOH and KOH aqueous
solution :
i- Form salts with phenolic alkaloids .
ii- Open a lactone ring ( if present ) .
iii- Cause hydrolysis of ester alkaloids .
5. Functions of alkaloids in the plants:
Established speculations concerning the role of
alkaloids in plants include the following .
1- They may act as protective against insects
and herbivores due to their bitterness and
toxicity .
2- End products of detoxification reactions.
3- They sometimes act as growth regulators .
4- Reserves substances ( especially nitrogen ) .
6. Nomenclature:
* By
agreement, chemical rules stated that the
name of all alkaloids should end in -ine .
* The names of alkaloids are obtained in
various ways:
6.1. From the generic name of the plant in
which they occur e.g. Atropine from Atropa
belladonna
 6.2. From the specific name of the
plant yielding them e.g. Cocaine from
6.4. From the physiological action they
produce e.g. Emetine that acts as an emetic .
6.5. Occasionally from the name of the
discoverer e.g. Pelletierine which was
discovered by Pelletier .
*Sometimes a prefix or suffix is added to the
name of the principal alkaloid to designate
another alkaloid from the same source.
Prefixes :
* Nor- designates N-demethylation or N-
demethoxylation e.g. nornicotine .
• Apo-designates dehydration e.g. apomorphine .
Iso- , pseudo- , neo- and epi- indicate different
types of isomers .
• Suffixes
-dine , designate isomerism e.g. quinidine
-inine , indicates a lower pharmacological
activity e.g. ergotaminine is less potent than
ergotamine .
7. Detection and identification :
Alkaloids are detected by Chemical tests .
Chemical tests commonly performed for detection
of alkaloids involve two types of reactions:
 7.1. Precipitation reactions :
These result in the production of amorphous
or crystalline precipitates of various colours .

• The precipitating reagent is added to a neutral

or slightly acidic aqueous solution of the
alkaloid salts.
* The alkaloidal precipitants are used in :
i. Testing the presence or absence of alkaloids
in crude extracts of plant materials .
ii. Testing for the exhaustion of the alkaloid
content in extraction procedure .
* Among the reagents most commonly
used are:
1- Mayer’s reagent which gives yellowish
– white precipitate with most alkaloids
except caffeine and dilute ephedrine .
2- Wagner’s reagent gives reddish-brown
precipitate .
3- Dragendorf’s reagent gives orange
reddish-brown precipitate .
4- Hager’s reagent gives yellow precipitate .
5- Tannic acid gives brown precipitate .
* Care must be taken in the application of
these tests as :
1. Certain alkaloids such as caffeine and some
others do not react .
2. False positive response may be obtained in
certain cases as most of the regents used
precipitate, tannins, proteins, coumarins and
certain flavonoids.
7.2. Colour reactions:
* These reactions are usually performed by the
addition of colouring reagent, to the solid free
bases to produce characteristic coloured
solutions .
* Examples are Froehd’s , Mandalin’s , Marquis’
reagents.
8. Extraction and isolation of alkaloids:
* The general procedures for the isolation of
alkaloids are largely based on :
1. The alkaline nature of most alkaloids and
their ability to form salts with acids and on .
2. The relative solubilities of the alkaloid bases
and their salts in water and various organic
solvents .
* For extraction of alkaloids in appreciable
amounts , generally one of the following methods
is applied:
8.1.Extraction with water or water-miscible
solvents:
1- The powdered plant material is extracted with
water or aqueous alcohol containing dilute acid
(alkaloids are extracted as salts ) .
2- The acidic extract is shaken with
chloroform (or other suitable organic solvent)
to remove pigments and other unwanted
materials .
3- The acid aqueous extract is treated with
dilute alkali to liberate the free bases which
are separated by filtration or extraction with
organic solvent
8.2. Extraction with water-immiscible solvents:
1-The powdered plant material is treated
with dilute alkali and extracted with an
organic solvent ( alkaloids are extracted as
free bases ) and the organic extract is
concentrated .
2- The concentrated organic extract is then
shaken with an aqueous acid and allow
to separate (alkaloid salts are now in the
aqueous liquid while many impurities
remain behind in the organic liquid).
3- The acidic aqueous liquid is then treated
with dilute alkali to liberate the free bases
which are separated by filtration or
extraction with organic solvents .
8.3. Distillation :
*Volatile liquid alkaloids such as nicotine and
coniine are most conveniently isolated by
distillation .
* An aqueous extract is made alkaline with
caustic soda or sodium carbonate and the
alkaloid distilled off in steam .
8.4. Sublimation :
Sublimable alkaloids, such as caffeine,
could be directly obtained from the dried
powdered plant material by sublimation .
N.B.
* Fatty drugs (e.g. seed) are defatted before
extraction using petroleum ether .(most
alkaloid are insoluble in this solvent) .
*The use of strong alkali is not recommended ,
to avoid saponification , which result in the
formation of strong emulsion.
• Ammonia is the alkali of choice because it
is :
1. Sufficiently basic to liberate most
alkaloids
2. Volatile and completely removed after
extraction .
9. Separation of individual alkaloids:
The separation of the required individual
alkaloids from the solution of total
alkaloids can be achieved by the following
methods:
 9.1. Fractional liberation : (Gradient pH
extraction ) :
* This method is suitable for separating
alkaloids of different basicity.
i)The crude mixture is dissolved in 2% tartaric
acid and extracted with organic solvent .
ii)The pH of the aqueous solution is gradually
increased and extracted, after each increment
with organic solvent .
9.2. Chromatographic techniques:
* These are the most suitable in case of
complex mixtures.

9.3. Distillation
9.4. Sublimation
9.5. Fractional crystallization:
* The method exploits the differences in solubility
of the components of the mixture in a particular
solvent.
*It is generally performed after derivatization to
salts such as oxalates ,tartarates and picrates.
10.Quantitative determination of alkaloids:
*Quantitative determination of alkaloids in
crude drugs , galenicals and
pharmaceutical preparations is performed
to determine :
1- The genuinness of the raw material .
2- Rate of deterioration of galenicals .
3- The best stage for collection of plant
material.
4- Conformity with the label claims .
5- Pharmacological potency .
alkaloids , quantitative separation of the
alkaloids must be done .
* When chloroform is used as a solvent , it
should not be evaporated to dryness ,
because some may be decomposed to hydrogen
chloride and phosgene and this will cause
partial neutralization , therefore , chloroform
should be evaporated to small volume , then
alcohol is added and evaporation is carried out
to dryness.
* The purified solvent-free crude alkaloidal
residue could be analysed by any of the
following procedures:
10.1. Volumetric titration methods:
* These are based on the quantitative
reactions of alkaloids with acids to from salts.
*They are simple and accurate. They include :
 10.1.1. Aqueous titration :
• This is carried by either :
1- Direct titration of the alcoholic solution of
the alkaloidal residue with standard acid ,or .
2- Dissolving the residue in a known volume of
standard acid and back titrating the unreacted
acid with a standard alkali .
10.1.2. Non-aqueous titration:
* This method is suitable for determination of
weak bases and small quantities of alkaloids .
* The purified alkaloidal residue is dissolved in
glacial acetic acid or chloroform and titrated
with standard perchloric acid .
 10.2. Gravimetric methods:
* These can be performed by :
10.2.1. Weighing the purified
alkaloidal residue . or
10.2.2. Precipitation of the alkaloids by
complexation and determination of the
weight of the precipitate .
• The major drawbacks of the gravimetric
methods are:
i. They are insensitive to micro-amounts of
alkaloids .
ii. Inconvenient for the determination of
volatile alkaloids .
iii. In the determination of alkaloids by
precipitation other materials like proteins
might also be precipitated.
 10.3. Optical methods :
* These can be applied for determination
of total or individual alkaloids and include:
colourimetric , spectrophotometric,
flourimetric and polarimetric spectroscopy.
 11. Identification of the alkaloids:
• This is carried out on pure compounds .

*The purity of the

alkaloids is determined by:
1- Chromatographic methods.
2- Constancy of melting point .
 *

The pure alkaloid is characterized ,where

possible by :
11.1. Chromatography (TLC ,GLC) .
11.2. Melting point data.
11.3 UV, IR , MS and NMR spectroscopy .
12. Classification of alkaloids:
* Alkaloids show great variety in their
botanical and biochemical origin , in
chemical structure and pharmacological
action .
* Consequently many systems of
classification are possible.
*Alkaloids are usually classified according
to the nature of the basic chemical
structure from which they derive .
* Accordingly ,two major groups are
distinguished viz ,the non- heterocyclic
and the heterocyclic alkaloids.
 13. NON-HETEROCYCLIC ALKALOIDS
(Proto alkaloids)
Alkaloids with exocyclic nitrogen
* The alkaloids of this group are also known as
biological amines .
* They are characterized by the absence of heterocyclic nitrogen atoms in their molecules .
• *They are derived from the amino acids
phenylalanine or tyrosine .
* They include the ephedra , khat , peyote,
colchicum and capsicum alkaloids .
 13.1. Ephedra alkaloids
13.1.1. Botanical source:
Various species of Ephedra (e.g.Ephedra
sinica) family Gnetaceae are used as source of
the alkaloids ephedrine and
pseudoephedrine.
13.1.2. Structure and properties :
 CH OH HO CH
CH NH CH3 CH NH CH3
CH3 CH3

()Ephedrine ()Pseudoephedrine
 * Ephedrine occurs as colourless crystals or
white powder or granules mp 40-43° C
* It is rather unusually stable among alkaloids .
• It can be heated at 100°C for several hours
without decomposition.
* However, ephedrine solutions decompose on
exposure to light in the presence of oxygen .
* The free base is volatile with steam .
* It does not give a precipitate with Mayers
reagent except when in concentrated solution.
 13.1.3. Preparation of ephedrine :
Ephedrine could be prepared by :
13.1.3.1. Isolation from the plant material :
*This is carried out by one of the following
methods :
1. Steam distillation after conversion to free base

2. Applying any of the usual procedures for

extraction of alkaloids using benzene as solvent .
• ( chloroform should not be used due to the
violent reaction with ephedrine upon
evaporation which results in ephedrine
hydrochloride with the release of the toxic
aldehyde phosgene ).
*The reaction also occurs in aged chloroformic
ephedrine solution .
3- Shaking with dilute HCl , which extracts
both ephedrine and pseudoephedrine as
hydrochloride salts followed by separation of
the mixture .
• 13.1.3.2. Fermentation:
* This is a commercial method for large-scale
production of dl- ephedrine in which :
1- A mixture of benzaldehyde and molasses is
allowed to ferment .
2- The resulting keto-alcohol.
(phenylacetylcarbinol) is treated with
methylamine and hydrogen to produce dl-
ephedrine (racemic form).
13.1.4. Separation of ephedrine from the less
active pseudoephedrine:
* Ephedrine can be separated from pseudo-
ephedrine in their oxalate forms by fractional
crystalization from cold water in which
ephedrine oxalate is much less soluble than
pseudoephedrine oxalate .
 13.1.5. Identity test :
13.1.5.1. Biuret reaction: ( Chen’s test ) :
On addition of few drops of copper
sulphate and sodium hydroxide solution to
the aqueous solution of ephedrine HCl , a
violet colour is produced .
• * When shaken with few mls of ether , the
ethereal layer acquired a purple colour
while the aqueous layer turns blue
* Under standardized conditions, this test can
be used for quantitative determination of
ephedrine .
 13.1.6. Uses :
* Ephedrine is used for the relief of asthma and
hay fever .
*Its action is more prolonged than that of
adrenaline and it can be taken orally.
*It is a potent nasal decongestant .
• 13.1.7. Toxicity
Nausea and vomiting, followed by insomnia,
cardiac arrhythmia, myocardial ischemia,
agitation, psychosis and seizures.
 13.2. Khat alkaloids
13.2.1. Botanical source:
* Khat or , “Abyssinian tea “ consists of the
fresh leaves of Catha edulis family
Celastraceae
* The major alkaloids are cathinone and cathine

* The young fresh leaves that come from the

tips of the branches contain the optimum
amount of cathinone .
* In older leaves , it is converted to the weakly
active compounds .Cathine ( (+) – norpseudo-
ephedrine ) 80% and (-) - Norephedrine
20% .
* This conversion also occurs during the
drying of young leaves.
 13.2.2. Structure and properties:

C O HO CH CH OH
H2N CH CH3 CH NH2 CH NH2
CH3 CH3
()Cathinone ()Cathine ()Norephedrine
13.2.3. Identity test :
* Cathine gives a positive Biuret reaction .
* Cathinone gives a positive test for ketones .
 13.2.4. Uses:
Cathinone is CNS stimulant. It has similar
pharmacological properties to the amphetamine
with a similar potency .
* The medicinal use of amphetamine has declined
markedly as drug dependence and severe
depression generated on withdrawal.
• 13.2.5. Toxicity:
• Significant sympathomimetic effects, as well
as psychosis, agitation, aggression, and
sometimes violent and bizarre behavior.
13.3. Capsicum alkaloids
13.3.1. Botanical source:
Capsaicin is the strongly pungent principle
isolated from the fruits of Capsicum annuum
family Solanaceae .
 13.3.2. Structure and properties :

O
CH3O
N
H
HO
Capsaicin
It is a phenolic amide alkaloid .
It possess weakly basic characters, due to
the presence of nitrogen in an amide
group Therefore , it can be extracted with
ether from a weakly acidic medium .
 13.3.3. Identity test :
* When a small amount of sucrose is added to a
solution of capsaicin in conc . H2SO4 a violet
colour is produced.
13.3.4. Uses:
Capsaicin is used as a counter– irritant in the
form of ointment, plaster, medicated wool… etc
for the relief of rheumatism, lumbago… etc.
• 13.3.4. Toxicity:
• Burning or stinging pain to the skin and if
ingested in large amounts by adults or small
amount by children, can cause nausea,
vomiting, abdominal pain and burning
diarrhea.
13.4. Peyote alkaloids :
13.4.1. Botanical source:
Peyote or Mescal buttons consists of the dried tops of
the cactus Lophophora williamsii family Cactaceae.
The drug contains several alkaloids the most
important of which is mescaline .
 13.4.2. Structure and properties

CH3O NH2

CH3O
OCH3

Mescaline
* Mescaline moderately soluble in water,
soluble in alcohol, chloroform and benzene and
insoluble in ether and petroleum ether .
13.4.3. Identity test:
* Mescaline gives with Marquis’ reagent an
orange colour .
13.4.4.Uses:
Hallucinogenic or psychomimetic in a dose of
400-700 mg by injection.

Mescaline was proved valuable in experimental

psychiatry.
* Habituation and addiction do not result from
repeated use of mescaline, so it is not regarded
as a narcotic drug .
13.4.5. Toxicity :
• Ingestion of mescal buttons results in mydriasis
accompanied by unusual and bizarre colour
perception .
 13.5. Colchicum alkaloids
13.5.1. Botanical source:
The principal alkaloid is colchicine
obtained from . Colchicum autumnale
family Liliaceae .
* The structures of colchicum alkaloids are
 13.5.2. Structure and properties:
CH3O
NH CO CH3
CH3O

O
R

Colchicine R = OCH3
Colchiceine R = OH
* It is a very weak base .
* It can be extracted with chloroform from both
acidic and alkaline solutions .
*On treatment with mild acids or alkalis ,
colchicine is converted to colchiceine .
13.5.3. Identity test :
* With ferric chloride colchicine gives a garnet-
red color and colchiceine gives an olive green
colour .
 13.5.4. Uses :
• Colchicine is mainly used for the treatment of
gout and it is effective in acute attacks .
• Its use has now been restricted due to its
high toxicity .
• 13.5.5. Toxicity:
• Initial symptoms include nausea, vomiting,
diarrhea and abdominal pain.
• Delayed symptoms include seizure, cardiac
dysrhythmias, hypotension, shock,
pancytopenia and respiratory, renal and
hepatic failure.
14.HETEROCYCLI
C ALKALOIDS
 14.1. Alkaloids of the pyridine group
• Alkaloids belonging to the pyridine group are
subclassified according to the building nuclei
into compounds containing them :
14.1. Pyridine nucleus only e.g. trigonelline
from foenugreek.
14.2. Pyridine nucleus with another nitrogenous ring
e.g. tobacco alkaloids .
14.3. Piperidine nucleus e.g. lobelia alkaloids .
14.4. Tetrahydropyridine nucleus e.g.Areca alkaloids.
14.5. Pyridone nucleus e.g. ricinine from castor seeds
• 14.1. Pyridine alkaloids
Trigonelline .14.1.1
:Botanical source .14.1.1.1
It occurs in the seeds of different plants such
as foenugreek (Trigonella foenum– graeccum
family Leguminosae), coffee , cannabis and
strophanthus .
. *It also occurs in soybeans and potatoes
14.1.1.2. Structure and properties:


COO

N
CH3
Trigonelline
• It It is very soluble in water, soluble in
alcohol, insoluble in ether and chloroform.
• It is excreted from urine after intake of
nicotinic acid .
• It is derived from nicotinic acid which is
biosynthesized from L – tryptophan .
• When heated with HCl it gives nicotinic acid
and methyl chloride .
• When heated with barium hydroxide it gives
methyl amine .
14.1.1.3. Uses:
Hypoglycaemic (as it slows down the
metabolism of nicotinic acid), cholesterol
lowering, anti– ulcer and anti-cancer
drug.
14.2. Pyridine nucleus with another nitrogenous
ring :
14.2.1. Tobacco alkaloids:
14.2.1.1. Botanical source:
They are obtained from the tobacco plants
(Nicotiana tabacum family Solanaceae ).
 14.2.1.2. Structure and properties:
Nicotine, nornicotine and anabasine are
volatile liquid alkaloidsN icotine
. R = CH 3
N N Nornicotine R = H
H R
N N
A nabasine
 Nicotine :
* It possess a narcotic odour .
* It can be distilled with steam .
* Nicotine is biosynthesized from nicotinic
acid and proline ( derived from L-
ornithine)
• It usually functions as a monoacidic base
when treated with acid in the presence of
various indicators ,but in case of excess acid it
unites with two molecules of monobasic acid.
• Nicotine decomposes upon exposure to UV
light to give nicotine N-oxide , nicotinic acid
and methylamine .
 14.2.1.3. Estimation of nicotine :
• The plant material is treated with NaOH
solution and the alkaloid is steam
distilled into a standard acid solution .
The uncombined acid is back titrated
with standard alkali .
14.2.1.4. Identity test :
On shaking an aqueous solution of nicotine
with vanillin in conc . HCl a red colour is
produced .
 14.2.1.5. Uses:
The principal use of nicotine is an insecticide.
Pharmaceuticaly it is used as nicotine
• 14.2.1.6. Toxicity :
• Nicotine is teratogenic in laboratory animals .
• Tobacco smoking contributes to
atherosclerosis and chronic bronchitis .
• Symptoms of poisoning include salivation,
nausea, vomiting , abdominal pain ,diarrhea,
headache , mental confusion and pronounced
weakness .
• These can lead to death by respiratory failure.
 14.3. Piperidine alkaloids
• Piperidine alkaloids are biosynthesized from
l-Lysine .
• This group include the alkaloids of lobelia ,
black pepper , pomegranate, conium and
castanospermum .
• 14.3. 1. Lobelia alkaloids(Indian tobacco)
• 14.3. 1.1. Lobeline is the most important
alkaloid among the alkaloids of Lobelia inflata
family Campanulaceae .
*Lobeline HCl is soluble in chloroform .
O N OH
CH3
 14.3.1.2. Identity test :
With Marqui’s reagent it gives a red–violet
colour .
14.3.1.3. Uses:
*Lobeline is used in spasmodic asthma and
chronic bronchitis .
An injection of lobeline HCl is used in the
resuscitation of new- born infants .
• 14.3.1.4. Toxicity:
• Nausea, vomiting, diarrhea, coughing,
dizziness, visual disturbances, hearing
disturbances, mental confusion, weakness,
slowed heart rate, hypertension, increased
breathing rate, tremors and seizures.
 14.3.2. Pepper alkaloids:
The fruits of Piper nigrum family
Piperaceae contain a number of alkaloids,
the chief one is piperine .
 14.3.2.1. Structure and properties:

N
O
O
*It decomposed easily with alcoholic potash to
yield piperidine and piperic acid .
* It is neutral and does not form stable salts .
14.3.2.2. Identity Test :
With H2SO4 it gives a red color .
14.3.2.3. Uses:
* It is used in certain tonics and rubefacient
preparations.
 14.3.2.4. Toxicity:
Prolonged use of piperine at high doses causes
loss of taste buds in the tongue .
 14.3.3. Pomegranate alkaloids :
14.3.3.1. Pelletierine :
* It is the most Important alkaloid of
pomegranate alkaloids ( Punica granatum
family Punicaceae )

CHO

N
H
 * It is soluble in water and organic solvents .
* It is an oily liquid that rapidly resinifies when
exposed to air.
* It volatalizes at ordinary temp .
14.3.3.2. Uses :
* Pelletierine is used in a form of pelletierine
tannate as a taenifuge .
 14.3.3.3. Toxicity of pelletierine
*The tannate form of pelletierine is used
because it is less soluble in the stomach , so it
is less able to be absorbed.
*Toxicity results in severe muscle cramps , and
sometimes convulsions .
*It is rarely used in anthelmintic today .
 14.3.4. Conium alkaloids:
* The major alkaloids of hemlock fruits Conium
maculatum family Umbelliferae are Coniine
and gamma-coniceine.
14.3.4.1. Structure and properties:

N N
H
(+)-Coniine -Coniceine
• Coniine is a colourless volatile oily liquid
with mice–like penetrating odour and a
burning taste .
• It is miscible with ethanol , ether and
acetone and slightly soluble in
chloroform .
 14.3.4.2. Identity test :
* With sodium nitroprusside solution, coniine
gives red colour that changes to violet or blue
on addition of acetaldehyde .
 14.3.4.3. Uses:
* Coniine is used as local analgesic, mostly
in external preparations , due to its high
toxicity .
It is used as an ointment for treatment of
haemorrhoids and anal fissures.
 14.3.4.4. Toxicity :
Initial symptoms may be vomiting , confusion,
respiratory depression and muscle paralysis.
Death, when it occurs, is usually rapid and due
to respiratory paralysis.
14.3.5. Castanospermum
14.3.5.1. Castanospermine
Castanospermine is the most important alkaloid
obtained from the seeds of Castanospermum
australe family Leguminosae.
• Castanospermine is a polyhydroxylated
alkaloid and in fact a sugar analogue
(compare with glucose), which explains its
activity against the glucosidase enzymes
involved in the formation of glycoprotein
which is important in the formation of viral
coating. Without the essential envelope
structure the virus would be unable to infect
healthy white blood cells.
14.3.5.2. Uses:
1. It is used for its antiviral (anti-HIV) and
anti- inflammatory (i.e. immunosuppressive)
activities. It has also been used in cancer
treatment ,but is not recommended in diabetes
due to toxicity most probably due to its
nonspecific inhibition of various glucosidases .
• Toxicity
• Toxic effects included weight loss, lethargy
and dose-dependent thrombocytopenia.
14.4. Tetrahydropyridine alkaloids

14.4.1. Areca nut (or Betel nut ) is the

dried seeds of Areca catechu family
Palmae or Arecaceae).
* Arecoline is the most important
alkaloid .
14.4.1.1. Structure and properties:

COOCH3

N
CH3
*It is a colourless oily liquid b.p. 2O9 C
freely miscible with water , ethanol , ether
and chloroform .
*Arecoline on treatment with HCl under
pressure is decomposed to methyl alcohol
and arecaidine .
 14.4.1.2. Identity tests :
Aqueous solution of arecoline with :
K- ferricyanide gives blue colour .
K-ferrocyanide gives green colour.
 14.4.1.3. Uses :
* Arecoline has a pronounced central
stimulant action , although large doses may
cause depression and paralysis .
* Areca is classified as an anthelmintic in
vetrinary medicine and is employed as a
vermicide and taenifuge.
 14.5. Pyridone alkaloids
14.5.1. Ricinine
It occurs in the
seeds of castor Ricinus communis
family Euphorbiaceae .
14.5.1.1. Structure and properties :

OCH3

C N

N O
CH3
* It is neutral and does not form salts with acids.
* It sublimes at 170 – 180 C under 20 mm pressure.
* It is sparingly soluble in cold water, alcohol
chloroform .and ether .
* It gives no precipitate with Mayer’s reagent.
 14.5.1.1.2. Isolation of ricinine:
* The defatted seeds are extracted with boiling
water. The solvent is evaporated under vacuum
and the residue extracted with boiling ethanol
Concentration of the ethanolic extract results
in
precipitation of crude ricinine which can be
recystallized from boiling water .
14.5.1.1.3. Identity test :
Ricinine with conc. HNO3 in a dish on a
water bath gives yellow residue which
changes on addition of ammonia to red .
 14.5.1.1.4. Toxicity of ricinine:
Ingestion of castor seeds causes nausea,
vomiting,haemarrhagic gastro- enteritis,
hepatic, and renal damage , convulsion,
coma , hypotension, respiratory
depression and death.
 14.6. Alkaloids of the Tropane group
* Tropane is a bicyclic compound formed
by
condensation of pyrrolidine and piperdine
with one nitrogen in common .
*Tropane base is derived from L-ornithine .
• Tropane alkaloids are esters of organic acids
(tropic , atropic , benzoic…etc ) combined
with one of a series of bicyclic hydramines :
• i. Hydroxytropane or
• Ii. Ecgonine
• Being esters , they are unstable towards acids
and alkalis and are thermolabile
 N CH3 N CH3
COOH

OH OH
Hydroxytropane Ecgonine
 14.6.1. Hydroxytropane
14.6.1.1. Solanaceous alkaloids:
* This name refers to alkaloids obtained
from plants of family Solanaceae which
have tropane nucleus and it does not
include the non-tropane alkaloids (e.g.
capsaicin, solanine, nicotine..etc) .
* Hyoscyamine (and its racemic form ,
atropine) and hyoscine (scopolamine ) are
the most important solanaceous alkaloids.
* They occur in a number of solanaceous
plants e.g. Atropa belladonna and Datura
stramonium
 N CH3
N CH3

O CH2OH
O CH2OH
O C CH
O C CH
O
(-)-Hyoscyamine (-)-Hyoscine
(±)-Atropine
* In most cases, atropine is not present in
the plant but results from the
racemization of (-)- hyoscyamine during
isolation.
 14.6.1.1.2. Conditions which cause
racemization of hyoscyamine are :
1- Heating under vacuum.
2- Caustic alkalis in cold alcoholic solution.
3- Ammonia .
4- Boiling chloroform.
 14.6.1.1.3. Hydrolysis
* Both hyoscyamine and atropine are readily
hydrolysed by aqueous solutions of mineral
acids as well as by NaOH and barium hydroxide
to yield tropic acid and tropine .
 N CH3 N CH3
CH2OH
hydrolysis
O CH2OH + HOOC CH
O C CH OH
O
Tropine Tropic acid
* Hyoscine is also hydrolysed under the same
conditions to yield tropic acid and scopoline
( oscine ) which is more stable than scopine .
 N CH3 N CH3
CH2OH
hydrolysis
CH COOH +
O CH2OH
HO O
O C CH
O Tropic acid Oscine
 14.6.1.1.4. Identity tests:
14.6.1.1.4.1. Vitali- Morin reaction:
* The test is given by tropic acid and its esters .
* The alkaloid is treated with fuming nitric acid . The
mixture is evaporated to dryness . To the residue in
acetone is then added few drops of KOH in
methanol a purple colour is produced which changes
to red and subsequently fades to colourless.
* Under standardized conditions this test may be used

for quantitative estimation of these alkaloids .

 14.6.1.1.4.2. Gerrard reaction :
* When few mgs of the alkaloid are treated
with 2% solution of mercuric chloride in
ethanol a red colour is produced in case of
atropine ( without warming ) and upon
warming with hyoscyamine .
* Hyoscine gives a white precipitate .
 14.6.1.1.5. Separation of hyoscyamine
from atropine:
* They can be separated in their oxalate forms
by fractional crystallization from acetone and
ether, in which hyoscyamine oxalate is more
soluble than atropine oxalate .
(i.e. atropine oxalate crystallizes first ) .
N.B.
Homatropine, a common synthetic substitute
for atropine can be distinguished from the
natural product by failure to give a positive
Vitali-Morin test .
N CH3

O OH
O C CH
 14.6.1.1.6. Uses:
* Hyoscyamine , atropine and hyoscine are
used as antispasmodics, mydriatics and to
decrease salivary and sweat glands secretions.
* In addition hyoscine has a sedative effect on
the CNS and used in motion sickness .
* Atropine and hyoscyamine are antidotes to
organophosphorus insecticides .
 14.6.1.1.7. Toxicity :
• Atropine is toxic in doses of 50 – 100 mg ; doses
of 10 mg or less may be lethal in children or
susceptible individuals .
• The symptoms develop within few hours and
include :
• Dry mouth , flushing of the face , redness of the
skin , dilatation of the pupils and rapid pulse .
 14.6.2. Ecgonine.
14.6.2.1. Coca alkaloids :
* The leaves of Erythroxylum coca family
Erythroxylaceae contain several alkaloids of
which cocaine , cinnamoylcocaine and alpha-
truxalline are the most important ones .
N CH3 O
C OCH3

O C
O
Cocaine
Ecgonine base contain both acidic and
alcoholic groups .
The acidic group is esterified in most cases
with CH3OH.
The alcoholic group is esterified with
different acids , giving different alkaloids.
 Cocaine can be hydrolysed by acids to give
ecgonine ,benzoic acid and methanol .

N CH3
N CH3 O
hydrolysis COOH
C OCH3
+ COOH + CH3OH
OH
O C
Ecgonine Benzoic acid Methanol
O
• Cocaine is a diester alkaloid.
It is liable to decomposition , thus its
aqueous solution is sterilized by filtration
through bacteriological filter (not by
autoclaving).
 14.6.2.2. Manufacture of cocaine from natural
sources:
*The process depends on the fact that cocaine,
cinnamoylcocaine and alpha- truxilline are
ecgonine derivatives which can be obtained by
acidic hydrolysis (HCl) of these alkaloids .
i) The ecgonine HCl is purified and converted
into a free base (by sodium carbonate ).
ii) On benzoylation with benzoic anhydride,
benzoylecgonine is obtained .
iii)Methylation of the latter with methyl iodide
and sodium methoxide in methanol will give
methylbenzoylecgonine .
 14.6.2.3. Identity test :
With p-dimethylaminobenzaldehyde (at
100c for 3 min) it gives a red colour .
14.6.2.4. Uses:
Cocaine is used as local anaesthetic in
ophthalmic and E.N.T. surgery .
It has a CNS stimulant effect, followed by a
hypnotic effect.
14.6.2.5. Toxicity :
• Common side effects include anxiety, increased
temperature, paranoia, restlessness and teeth
grinding.
• With prolonged use the drug can cause insomnia,
tachycardia, hallucination and paranoid
delusions.
Possible lethal side effects include rapid
heartbeat, abnormal rhythms, tremors,
convulsions, renal failure, heart attack, stroke
and heart failure.
 14.7. Alkaloids of the Quinoline group
These are biosynthesized from tryptophan
.
14.7.1. Cinchona alkaloids
The most important alkaloids of Cinchona
succirubra family Rubiaceae are pairs of
stereo isomers :
(-) - quinine and (+) - quinidine .
• 14.7.1.1. Structure and properties:
The basic skeleton of cinchona alkaloids is
ruban-9-ol ( derived from the parent compound
ruban , named after family Rubiaceae ) .
• Ruban nucleus is a combined skeleton formed
from a quinoline ring attached through an
asymmetric carbon to a quinuclidine ring .
 CH CH2

N
CH OH
R
Quinine, quinidine R = OCH3
Cinchonine, cinchonidine R = H
N
• Cinchona alkaloids are di-acidic bases of
chiefly quinic , cinchotannic and quinovic
acids .
• Quinine solubility in ether is greater than that
of other cinchona alkaloids and this property is
often utilized in separating it from the other
alkaloids .
The tartarates of cinchonine and quinidine are
water – soluble , while those of quinine and
cinchonidine are water-insoluble .
 14.7.1.2. Isolation :
The separation is based on the difference in
solubility of the different alkaloids and their salts .
The bisulphates of the alkaloids are readily
soluble in water .
The monosulphate of quinine (B. HSO4 ) is
sparingly soluble in water.
Cinchonine is almost insoluble in ether.
 14.7.1.3. Identity tests :
14.7.1.3.1. Thalleiquin test .
When few drops of bromine water are added
to a weakly acidic solution of quinine salt ,
followed by the addition of strong ammonia ,

a characteristic emerald green colour is

produced.
The reaction is also given by quinidine but not
by cinchonine or cinchonidine .
 14.7.1.3.2. Ferrocyanide test :
A small quantity of quinidine is mixed with bromine
water in an evaporating dish , and transferred to
a test tube with the aid of water , chloroform is then
added and the solution is allowed to stand, for few
minutes . A drop of 10% solution of K-ferrocyanide
and NaOH are added with shaking or sterring . The
chloroform layer assume a red colour.
In case of quinine salt the chloroform layer remains
colourless .
 14.7.1.4. Uses :
Quinine is anti- malarial .
Quinidine is anti- arrhythmic and anti- malarial.
14.7.1.5. Structure requirements for antimalarial
activity :
Removal of the vinyl group results in loss of
activity
Replacement of the central CHOH by CHCl ,CH2, CO
or acylation decreases the activity.
• 14.7.1.6. Toxicity
• Quinine toxicity (Cinchonism) characterized by
tinnitus, headache, disturbed vision and occasionally
deafness and anaphylactic shock may be seen.
• Cardiovascular toxicity is similar to quinidine toxicity;
quinine causes myocardial depression and prepheral
vasodilatation. In addition, renal failure, haemolytic
anemia and hypoprothrombinemia.
 Powdered bark
-Alkalinization with CaO+NaOH+H2O (Liberatn of free bases
and pptn of tannins) .
- Reflux with benzene .
- Filtratn while hot .

Benzene filtrate
(Alkaloidal bases))

-Acidificatn with dil H2SO4

Acidic aqueous layer

(Alkaloidal bisulphates)
- Heating
- Adjusting pH to 6.5 with Na2CO3
 (sulphates of quinidine,cinchonine,cinchonidine) ( Quimine sulphate)
-Alkalinization with NaOH . - Addn of boiling
Acqueous soln - Extraction with ether . precipitate H 2o .
- Na 2CO3
Quinine

( Quinidine and cinchidine ) - Evaporatn

- Extract with dil HCl - Extratn with
Ether layer - Neutralizatn Aqueus layer
alcohol
- Addn of Na k tartarate - Concentn and
- Filtratn crystalliztion
Cinchonine
 ( Cinchonidine tartarate.) ( Quinidine tartarate)
- Acidificatn with dil HCI - Addn of KI

Precipitate Cinchonidine HCI Filtrate Quinidine HI

- Alkalinization with NH4OH - Alkalinization with NH 4OH

Cinchonidine Quinidine

Extraction and isolation of Cinchona alkaloids

The most important alkaloids belonging to this
group are those present in ipecacuanha , opium
and curare .
They are biosynthesized from tyrosine .
14.8.1. Opium alkaloids
Opium is the air – dried latex , obtained by
incision from the unripe capsules of Papaver
somniferum family Papaveraceae .
groups:
1. Morphine and related alkaloids which
contain a structural nucleus related to
phenanthrene .
2. Alkaloids which contain benzylisoquinoline
nucleus.
• 14.8.1.1. Morphine group :
Morphine and codeine are the major ones in
this group .
• Ethylmorphine and heroin (diacetylmorphine)
do not occur in opium as such but are
prepared by chemical means from the
naturally occurring alkaloid.
 N CH3
R1 R2
Morphine H H
Codeine CH3 H
Heroin CH3CO CH3CO

OR1 O OR2
chloroform , nearly insoluble in ether or
benzene .
* Codeine is soluble in cold benzene .
• 14.8.1.1. 2. Identity tests :
* With Marquis reagent both morphine and
codeine give a violet colour .
* With neutral ferric chloride solution
morphine gives blue colour while codeine
gives no colour .
 14.8.1.2. Benzylisoquinoline alkaloids .
The major alkaloids of this group are
papaverine and noscapine ( narcotine ) .
CH3O

N
CH3O

Papaverine
CH3O
OCH3
* Papaverine and noscapine are very weak
bases, and due to this fact they can be
extracted ( as free bases) with chloroform
from weakly acidic solution .
 14.8.1.3. Identity test :
* With Mandalin’s reagent , papaverine
gives a greyish – green colour.
* Heating narcotine with conc . H2SO4
gives a distinct violet colour .
* By this test , narcotine can be detected
 Meconic acid
Opium alkaloids usually occur naturally
combined with meconic acid .

O
OH

HOOC O COOH
* Meconic acid gives with FeCl3 solution a
purplish red coloured complex that is not
destroyed by cold dilute HCl or mercuric
chloride solution .
 14.8.1.4. Uses:
*Opium is an antidiarrhoeal drug .
* Morphine is a narcotic analgesic .
* Codeine is antitussive .
* Papaverine is antispasmodic and for the
treatment of male impotence .
* Noscapine is antitussive and
antispasmodic
 14.8.1.5. Toxicity :
• Acute poisoning by morphine is seen in
higher doses with depressed respiration,
increased CNS depression , pinpoint
pupil , flushing and finally cyanosis .
14.8.2. Ipecacuanha alkaloids
The most important alkaloids isolated from
the root and rhizomes of Cephaelis
ipecacuanha family Rubiaceae are emetine,
cephaeline and psychotrine.
 RO
OCH3
NH OCH3
CH3O

N
H5C2

Cephaelin R = H
Emetine R = CH3
 HO
OCH3
N OCH3
C H 3O

N
H 5C 2
P sy c h o tr in e
• Cephaeline and psychotrine are
phenolics while emetine is non-
phenolic .
Emetine is soluble in ether , cephaeline
slightly soluble while psychotrine is
insoluble .
 14.8.2.1. Separation :
* In an aqueous acid extract obtained from a
preliminary extraction of total alkaloids
from , lpecac . emetine , cephaeline and
psychotrine may be separated as follows:
1. When the aqueous acid extract is treated
with an excess of NaOH solution , the
alkaloids are converted to their free bases
form , and emetine is precipitated which may
be removed by filtration or extraction with
ether , while cephaeline and psychotrine
remain dissolved in the aqueous layer
(phenate salts) .
2. To extract the latter alkaloids ,the solution is
first neutralized with HCl, then made alkaline
with ammonia and extracted with ether which
will extract cephaeline .
* To extract psychotrine the aqueous alkaline
solution is extracted with chloroform .
14.8.2.2. Identity test :
With Froehd’s reagent :
Psychotrine gives a pale green colour
Emetine and cephaeline give a dirty greenish
- yellow colour, which in case of emetine
fades on the addition of a drop of HCI while
that of cephaeline changes to dull greenish –
blue.
14.8.2.3. Uses:
* Emetine is used for the treatment of
amoebic dysentery.
* Emetine , cephaeline and psychotrine are
emetic drugs . Psychotrine is a selective
inhibitor of human immunodeficiency virus
(HIV).
 14.8.3. Curare alkaloids
The term “curare” is a generic one applied to
various South American arrow poisons.
These extracts are made of a number of
different plants particularly members of the
families Menispermaceae and Loganiaceae .
• Among the several alkaloids which have been
isolated from curare (+) – tubocurarine chloride
is the only one that is of therapeutic
importance at present .
C H 3O

CH3
N
HO CH3
O CH2

CH OH
CH3 O
N
CH3

OCH3

(+ )-T u b o c u r a r in e
 Tubocurarine is soluble in water or alcohol ,
insoluble in ether or chloroform.

14.8.3.1. Identity test :

Addition of sodium carbonate solution to a
solution of d-tubocuraine chloride produces a
yellow– brown precipitate .
14.8.3.2. Uses :
Tubocurarine chloride is mainly used as
skeletal muscle relaxant in surgical
operations without deep anaesthesia and in
certain neurological conditions .
14.8.3.3. Toxicity
Unability to move any voluntary muscles,
including the diaphragm. A large enough
dose will therefore result in death from
respiratory failure.
 14.9. Alkaloids of the Indole group
They are biosynthesized from tryptophan .
The important medicinal alkaloids
belonging to this group are those of ergot ,
rauwolfia, physostigma, nux vomica ,
vinca and yohimba .
 14.9.1. Ergot alkaloids
Ergot is the dried sclerotia of the fungus
Claviceps purpurea family Claviceptaceae ,
growing on cereals, usually the rye plant
(Secale cereale ) family Gramineae .
Ergot contains 12 major alkaloids, divided
into 6 pairs, according to their peptide
moieties.
 Leavo - Dextro –
Ergometrine Ergometrinine

(Ergonovine,Ergobasine)
Ergotamine Ergotaminine
Ergosine Ergosinine
Ergocrystine Ergocrystinine
Ergocryptine Ergocryptinine
Ergocornine Ergocorninine
 Ergot alkaloids of medicinal importance are
substituted amide derivatives of Lysergic acid.
Their isomers of isolysergic acid are practically
inactive pharmacologically .
 COOH COOH
7
8 6N CH3 N CH3
9
5
10 4
11 3
12 2
16
1
13 15
NH NH
14

Lysergic acid Isolysergic acid

Members related to lysergic acid are leavo– and
designated by the suffix - ine . They are
converted to the corresponding isolysergic acid
members by refluxing their methanolic or
ethanolic solutions with alcoholic KOH.
Members related to isolysergic acid are
designated by the suffix - inine . They are
converted to the corresponding lysergic
acid members by refluxing their alcoholic
solutions with phosphoric or acetic acids .
* In badly stored aqueous solutions i.e. when
exposed to excessive light or irradiated with UV
light , ergot alkaloids are converted to the
inactive lumi – products.
• These are nonfluorescent compounds in
which the double bond between C – 9 and
C – 10 is reduced and a OH group is
introduced at C – 10
• Normal ergot alkaloids are fluorescent
compounds .
14.9.1.1. Identity test :
Ergot alkaloids give characteristic deep blue
colour with Van Urk reagent .
 14.9.1.2. Ergot alkaloids of pharmaceutical
importance :
The most widely medicinally used ergot
alkaloids are ergometrine and ergotamine .
Ergometrine (Ergonovine):
 CH3
CO NH CH CHOH
N CH3

NH

()Ergometrine
It is soluble in water .
On alkaline hydrolysis it yields lysergic acid and
2 – aminopropanol.
Acidic hydrolysis by HCl destroys the lysergic acid .
 Ergotamine

CH3
OH
O
O C NH N
N CH3 N
O O
CH2

NH

()Ergotamine
phenylalanine.
Acidic hydrolysis by HCI destroys the lysergic
acid .

14.9.1.3. Uses:
Ergometrine is oxytocic .
Ergotamine is specific analgesic for migraine
 14.9.1.4. Toxicity :
• The poisoning from ingestion of bread made
from contaminated grains is highly
unpleasant , with victims complaining of
burning , “fire – like” sensations throughout
their extremities and of vivid highly coloured
hallucinations .
• These poisons can cause massive constriction of
blood vessels , leading to “blackened” limbs and
gangrene .
• This condition became known as St Antony`s fire .
 14.9.2. Rauwolfia alkaloids :
Rauwolfia consists of the dried roots and
rhizomes of Rauwolfia serpentina family
Apocynaceae .
The most important alkaloids are reserpine ,
recinnamine and deserpidine.
 N
CH3O N

OCH3

O CO OCH3
CH3OOC
OCH3 OCH3

()Reserpine
 Reserpine is a diester alkaloid.
On hydrolysis reserpine yields reserpic acid,
trimethoxybenzoic acid and methanol .
14.9.2.1. Identity test :
With vanillin / HCl reagent , reserpine gives a
rose –pink colour.
14.9.2.2. Uses:
Reserpine and related alkaloids are
antihypertensives and tranquilizers .
 14.9.3. Vinca alkaloids :
Catharanthus roseus family Apocynaceae contains
a number of alkaloids the most important of which
are vinblastine and vincristine . They are prepared .
as sulphate and stored in sealed ampoules in a
refrigerator .
14.9.3.1. Identity test :
Vanillin HCL reagent gives with vinblastine a pink
colour and an orange yellow colour with vincristine .
 14.9.3.2. Uses :
Vinblastine is used for the treatment of .
Hodgkin’s disease and carcinoma resistant to
other therapy .
Vincristine is used for treatment of leukaemia
in children .
 Vinorelbine is a newer, orally active , semi —
synthetic derivative of vinblastine, it has broader
anticancer activity and lower side effects.
 14.9.4. Physostigma ( Calabar bean )
alkaloids :
14.9.4.1. Physostigmine (eserine ) is the most
important alkaloid of Physostigma venonosum
familyCH
Leguminosae.
3 CH3
CH3 HN C O
HO
N
N N
CH3 N
CH3 CH3
CH3
Eserine Eseroline
Eserine on alkaline hydrolysis yields eseroline ,
methylamine and CO2 .
On exposure to air it oxidizes into rubreserine
(red compound ) and should therefore , be
protected from air and light .
14.9.4.2. Identity test :
Eserine gives a yellowish – brown colour with
Mandalin’s reagent .
14.9.4.3. Uses:
It is mainly used as a myotic drug.
With Alzheimer’s disease it has show some
evidence of inducing a slight improvement in
the intellectual and cognitive performance .
14.9.5. Alkaloids of Nux vomica:
The most important alkaloids of Strychnos
nux–vomica family Loganiaceae , are strychnine
and brucine .
14.9.5. Identity test :
Strychnine when treated with a trace of nitric acid gives
a yellow colour , while brucine give a red colour.
14.9.5. Uses :
Strychnine is extremely toxic
It is used in vetrinary medicine as CNS stimulant & tonic
It is used as antidote in barbiturate poisoning .
 14.9.6. Yohimba alkaloids :
The major alkaloid in the bark of Pausinystalia
yohimbe family Rubiaceae , is yohimbine
(aphrodine)
14.9.6.1 Identity test :
With Mandalin’s reagent , yohimbine gives a
blue colour that turns to green .
14.9.6.2. Uses :
yohimbine is an aphrodisiac .
14.10. Alkaloids of the imidazole group
14.10.1. Pilocarpus (Jaborandi )
alkaloids :
The most important alkaloid obtained from
Pilocarpus microphyllus family Rutaceae , is
H5C2 pilocarpine
CH2 . N CH3

O O N
Pilocarpine is an oily non – volatile liquid
It is soluble in water , alcohol or chloroform ,
nearly insoluble in ether .
The lactone ring is opened by caustic alkali , but
is unaffected by ammonia or carbonates.
The opening of the lactone ring leads to loss of
physiological activity
 14.10.2. Identity test :
With Helch’s test pilocarpine give a blue colour
14.10.3. Uses :
Pilocarpine is mainly used as a myotic drug .
In early glaucoma treatment it serve to increase
the irrigation of the eye and relief pressure .
Oral pilocarpine is used to relief dry mouth
resulting from radiation treatment for head or
neck cancer .
 14.11. Alkaloids of the purine group
Purine itself does not occur in nature but
numerous derivatives are biologically
significant.
The Pharmaceutically important bases of this
group are all methylated derivatives of 2,6 –
dioxypurine ( xanthine ) .
• Three well – known examples are :
Caffeine (1,3,7–trimethylxanthine ) .
Theophylline ( 1,3-dimethylxanthine).
Theobromine ( 3,7- dimethylxanthine ).
They occur in tea leaves Camellia sinensis
family Theaceae in coffee seeds Coffea
arabica family Rubiaceae and in cocao
seeds . Theobroma cocao family Sterculaceae.
 R3
O
1
R N R1 R2 R3
6
N1 5
7 8
Caffeine CH3 CH3 CH3
2 3 4 9
O N Theophylline CH3 CH3 H
N Theobrimine H CH3 CH3
R2
 14.11.1. Caffeine :
Caffeine sublimes without decomposition
It is soluble in water , more in hot water , alcohol ,
chloroform and sparingly soluble in ether .
Caffeine do not give precipitate with the known
alkaloidal precipitants.
 14.11.2. Isolation and separation:
The isolation and separation of the three purine bases
depend on the difference in their solubilities in organic
solvents , as well as their solubilities in alkalies.
They can be separated as follows .
1- Add NaOH solution to the mixture and extract with
benzene ( both theobromine and theoplylline are
soluble in aqueous solution of NaOH while caffeine
is
insoluble ). Distillation of benzene will give Caffeine .
2- Acidify with dilute HCl and then alkalinize with
dilute solution of ammonia and extract with
chloroform ( ammonia dissolves theophylline
leaving theobromine insoluble ) . Evaporation of
chloroform will give Theobromine .
3- Reacidify with dilute HCI and extract with
chloroform .
Evaporation of the solvent will give
Theophylline.
14.11.3. Identity test :
Murexide test :
Crystals of caffeine are treated with few drops of
conc HCI and traces of potassium chlorate , then
evaporated to dryness and the residue is
exposed to ammonia vapour a purple colour is
produced. The test is also given by theophylline
and theobromine .
 14.11.4. Uses :
Caffeine and its related compounds are CNS
stimulants .
Theophylline is a smooth muscle relaxant thus
used as bronchodilator. It also exert a diuretic
effect .
Theobromine is used mainly as a diuretic. It has
little stimulant effect on the CNS, hence it is
preferred over caffeine in cardiac oedema and
in angina pectoris.
• 14.11.5. Caffeine toxicity:
• Restlessness, anxiety, excitement, insomnia,
flushing of the face, increased urination,
gastrointestinal disturbance, muscle
twitching and irregular or rapid heart beat.
 14.12. Steroidal alkaloids
Steroidal alkaloids arise by the induction of a
basic nitrogen at some point in the steroidal
molecule .
The steroidal alkaloids of medicinal significance
are those of veratrum and solanum species .
 14.12.1. Veratrum alkaloids :
A large number of steroidal alkaloids have
been isolated from various veratrum
species e.g. Veratrum album family
Liliaceae.
Three groups may be distinguished from
among the alkaloids occurring in these
species .
 1. Alkamines

NH
HO

HO

Veratramin
2- Glycosidic alkaloids: veratrosine (veratramine +
D – Glucose )
3- Ester alkaloids: Protoveratrine A and B .
14.12.1.1. Uses :
Veratrum plant extracts and the alkaloids( mainly
protoveratrine A and B) have been used in the
treatment of toxaemia of pregnancy and for
mangement of hypertensive crises and
eclampsia .
 14.12.2. Solanum alkaloids :
Many solanum species e.g. Solanum tuberosum
family Solanaceae contain glycosidal alkaloids .

Glu Gd O
Rham Solanine
Solanine is soluble in hot ethanol , dilute acids
and amyl alcohol .
It is insoluble in water , chloroform and ether
Its solution in hot amyl or ethyl alcohol forms
a jelly on cooling .
 14.12.1.1. Identity test :
Solanine when treated with Marquis reagent a
yellow colour is produced which turns to violet .

14.12.1.2. Uses :
The aglycone , solanidine, is used as a starting
material for the synthesis of steroidal drugs .
• 14.12.1.3. Toxicity:
• Nausea, vomiting, diarrhea, stomach cramps ,
burning of the throat, cardiac dysrhythmia,
nightmares, itching, eczema, inflammation
and pain in the joints.
Biogenesis of tropane alkaloids :
. As the characteristic alkaloids of the group are
esters of hydroxytropanes and various acids ,
there are , for each alkaloid there are ,Hwo
distinct biogenetic moieties .
. Tropane moiety :
. Work with isotopes indicated that ornithine
and
acetate were precursors of the tropane
nucleus
. The tropic acid fragment is derived from
phenylalanine