UNIT- 2

ALKALOIDS
Presented By : Gitanjali Rohit
 INDEX
 General introduction of alkaloids

 Study of Composition & chemistry ,chemical classes,

biological sources of alkaloid

 Therapeutic use of alkaloids

 Commercial application of alkaloids.

DISCOVERY OF ALKALOIDS

 In 1804, the German chemist Fredrich Serturner isolated

from opium a ‘soporific principle’ which he called
‘Morphium’ in honour of Morphoeus, the Greek God of
dreams.

 The term ‘Morphine’ was given by the French physicist

Josph Gay-Lussac.

 The name ‘alkaloids’ (German Alkaloide) was introduced

in 1819 by thye German chemist Carl F W Meissner.
 WHAT ARE ALKALOIDS?
 Definition1: The term “alkaloid” (alkali –like) is commonly used to
designate basic hetrocyclic nitrogenous compounds of plant of plant
origin that are physiologically active.
 Definition 2: Alkaloids are cyclic organic compounds containing nitrogen
in negative state of oxidation with limited distribution among living
organisms.
 They are bitter in taste & derived from amino acids.
 Alkaloids usually contain one nitrogen atom but some may contain 5
nitrogen atoms such as ergotamine. The nitrogen may exist as a primary
amine (RNH2), secondary amine (R2NH), tertiary amine (RN), or as
quaternary.
P ROPERTIES OF ALKALOIDS
Physical properties
Most alkaloids are crystalline solids. Some are liquids that are
either:
Volatile: e.g. Nicotine and Coniine.

Non-volatile: e.g. Pilocarpine and Hyoscine

Color: The majority of alkaloids are colorless but some are colored

e.g.: Colchicine and Berberine are yellow.

Solubility: Both alkaloidal bases and their salts are soluble in

alcohol.
 Generally, the bases are soluble in organic solvents and insoluble in
water
 Exceptions in solubility:

 Bases soluble in water: caffeine, ephedrine, codeine, colchicine,

pilocarpine and quaternary ammonium bases.

 Bases insoluble or sparingly soluble in certain organic

solvents: Morphine and psychotrine 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: e.g. quinine monosulphate

 Salts soluble in organic solvents: e.g. Lobeline hydrochlorides

soluble in chloroform.
OPTICAL ACTIVITY:
 Many alkaloids are optically active due to the presence of
one or more asymmetric carbon atom (chiral) in their
molecule.
 Optically active isomers show different physiological
activities.
 Usually, the l (-) isomer is more active than the d (+) isomer
 E.g. l-ephedrine is 3 times more active than d-ephedrine
 l-ergotamine is 3 times more active than d-ergotamine.

 Exceptions:
 d-Tubocurarine is more active than the corresponding l-
form.
 Both quinine (l-form) and its d- isomer quinidine are active.
 The racemic dl-atropine is physiologically active.
CHEMICAL CHARACTERS:

 Basicity:
> The unshared electron pairs on the nitrogen atom
is responsible for alkaloidal basicity.

Strong basic alkaloids can form salts even with

very weak acids. While weak bases require more
acidic medium.

Amphoteric alkaloids (e.g. morphine, psychotrine

and cephaline contain a phenolic group and
narceine contains - COOH group)
CHEMICAL PROPERTIES
 In addition to carbon, hydrogen and nitrogen, most alkaloids
contain oxygen in their molecules.
 Few alkaloids are oxygen-free such as nicotine and coniine.
Salt formation
 Due to their basic character, alkaloids with acids make salts.
 Strong bases form salts with very weak acids.
 Weak bases require stronger acids.
 Dibasic alkaloids may form two series of salts.
 Very weak bases form unstable salts, e.g. piperine,
papaverine, narcotine and caffeine.
 Amphoteric alkaloids (e.g. containing phenolic or carboxylic
groups) can form salts with both acids and alkalis.
 Alkaloids showing acidic characters do not form salts with
acids e.g. ricinine.
Function of alkaloids in plants:

1) They may act as protective against insects and

herbivores due to their bitterness and toxicity.
2) They are, in certain cases, the final products of
detoxification in metabolic reactions, therefore
considered as waste products of metabolism.
3) They may provide nitrogen to the plant organs in
case of nitrogen deficiency (source of nitrogen).
4) They, sometimes, act as growth regulators in certain
metabolic systems.
5) They may be utilized as a source of energy in case of
deficiency in carbon dioxide assimilation, especially
those alkaloids containing a sugar moiety.
Function of alkaloids in plants:

Some alkaloids are extremely poisonous e.g.:

•Ergot alkaloids caused epidemic poisoning in the

Middle Ages in Europe as a result of feeding on rye
bread contaminated with the fungus.

•The extracts of plants containing such alkaloids have

long been used as arrow poisons in hunting and
warfare e.g. curare extract that contains tubocurarine
alkaloid.

•Certain were employed in this respect, as a draught

for execution e.g. Socrate’s execution, in ancient
Greece, with hemlock which contains coniine.
Function of alkaloids in plants:

-At the time of the Roman Empire, Belladonna (the

source of atropine) has been mixed with food with the
purpose of murdering.

- Cleopatra, the queen of Egypt used Egyptian

henbane (Hyoscyamus muticus) that contains
hyoscyamine, for suicidal purpose.

-Certain alkaloids are widely used for their

psychotropic effects e.g. caffeine acts as CNS stimulant
and nicotine is responsible of the psychological and
physical dependence of tobacco.
 S OURCES AND OCCURRENCE OF A LKALOIDS

 Alkaloids can occur in plant kingdoms; among the

angiosperms, the Leguminosae, Papaveraceae,
Ranunculaceae, Rubiaceae, Solanaceae, and
Berberidaceae are outstanding alkaloid-yielding
plants.

 The Labiatae and Rosaceae are almost free of

alkaloids; the gymnosperms only rarely contain them
(Taxaceae).
 Specific alkaloids are confined to specific plant families
such as hyoscyamine in Solanaceae, colchicine in
Liliaceae

 Occur in fungi (e.g ergot from Claviceps purpurea)

 Occur in various parts of the plant; in seeds

(physostigma, areca), underground stems
(sanguinaria), roots (belladonna root), rhizomes and
roots (ipecac, hydrastis), barks (cinchona).
Nomenclature of Alkaloid:

Alkaloids terminate with the suffix-ine, their names

may be derived from the:

Genus name e.g., Atropine from Atropa.

Species name, e.g., Cocaine from Coca.

Common name, e.g., Ergotamine from Ergot.

Physiological activity, e.g. Emetine (emetic).

Discoverer, e.g., Pelletierine from Pelletier.

Prefixes and suffixes:
Prefixes:
"Nor-”designates N-demethylation
e.g. Norpseudoephedrine and Nornicotine

"Apo-” designates dehydration

e.g. Apomorphine.

"Iso-, pseudo-, neo-, and epi-” indicate different types of isomers.

Nornicotine Nicotine Morphine Apomorphine

 SUFFIXES:

"-dine" designates isomerism as in the case of the Cinchona

alkaloids, quinidine and cinchonidine are the optical isomers of
quinine and cinchonine, respectively.
Classification of Alkaloids

Different systems of classification based on:

▪ The pharmacological action (biological activity)

▪ The chemical structure (type of nitrogen,

heterocyclic or non-heterocyclic and type of ring
structure)

▪ The biochemical origin (biosynthetic pathway of

production in the plant)

▪ The taxonomical origin (plant families rich in

alkaloids)
According to Hegnauer’s classification, which is based on
both the type of nitrogen and the biochemical origin,
three main types of alkaloids are distinguished:

•True alkaloids: these are derived from amino acids

and have nitrogen in a heterocyclic ring.

•Protoalkaloids: these are derived from amino acids and do

not have nitrogen in a heterocyclic ring.

•Pseudo alkaloids: these are not derived from amino acids

but have nitrogen in a heterocyclic ring.

Type of alkaloid Precursor Type of nitrogen

True alkaloids Amino acids Heterocyclic

Protoalkaloids Amino acids Non-heterocyclic

Pseudoalkaloids Non-amino acids Heterocyclic

 CLASSIFICATION OF ALKALOIDS
1) Pharmacological action (Biological activity)
Analgesics e.g. Morphine and Codeine
CNS stimulants e.g. Caffeine and Strychnine
Anti-cancers e.g. Vincristine, Vinblastine and Taxol
Mydriatics e.g. Atropine
Myotics e.g. Pilocarpine
Anti-asthmatics e.g. Ephedrine
Anti-tussives e.g. Codeine
Expectorants e.g. Lobelline
Anti-hypertensives e.g. Reserpine
Smooth muscle relaxants e.g. Atropine and Papaverine
Skeletal muscle relaxants e.g. Tubocurarine
Anthelmintics e.g. Pelletierine
Antiparasitics e.g. Quinine and Emetine
2) Chemical structure:
A-types of nitrogen, Heterocyclic or non- heterocyclic
a) Non-Heterocyclic or atypical alkaloids
* Sometimes called Protoalkaloids or Biological
amines e.g. Ephedrine, Colchicine, and Taxol.
* All have exocyclic N-atoms.

B- according to type of ring structure.

b) Heterocyclic or typical alkaloids which sub-
divided into several groups according to their ring
structure.
According to type of ring structure:
3- Alkaloids are classified according to the amino acid that
provides both the nitrogen atom and the fundamental portion
of the alkaloid skeleton.
Amino acid Alkaloid skeleton
Ornithine Pyrrolidine and tropane alkaloids
Lysine piperidine, quinolizidine, and indolizidine alkaloids
Nicotinic pyridine alkaloids
acid
Tyrosine phenylethylamines and simple tetrahydroisoquinoline
alkaloids,
Tryptophan simple indole, simple β-carboline,
terpenoid indole, quinoline, pyrroloindole, and ergot
alkaloids
Anthranilic acts as a precursor to quinazoline, quinoline and
acid acridine alkaloids

Histidine imidazole derivatives

The Nitrogen atom in Alkaloids
Number of nitrogen atoms:
*The alkaloids must have at least one nitrogen
atom in their structures

* Alkaloids may contain more than one up to 5

nitrogen atoms
e.g. Nicotine (2 N atoms), Ergotamine (5 N atoms).
TYPE OF AMINO GROUP:

1)A primary amino group e.g: Nor-pseudoephedrine.

2) A secondary amino group: e.g. Ephedrine

3) A tertiary amino group: e.g. Nicotine and Atropine.

4) A quaternary ammonium ion: e.g. Tubocurarine

TESTS FOR DETECTION AND IDENTIFICATION
Name of Composition Remarks
reagent
Alkaloidal Creamy white (positive with
precipitants: most alkaloids, except caffeine
1.Mayer's Potassium-mercuric iodide and dilute ephedrine).

2. Wagner's Iodine in potassium iodide Reddish brown ppt

3. Hager's Saturated solution of picric Yellow ppt

Orange-reddish brown
4.Dragendorff’s acid Potassium bismuth

5. Murexide test
for Purine alkaloid alloxantin with ammonia to
Purple colour
100 °C
GENERAL EXTRACTION AND SEPARATION OF ALKALOIDS

Powdered plant material

Petroleum ether

Extract Defatted powder

Total alkaloids
Fats &
Non-alkaloidal impurities
1 Alcohol
2 CHCl3
3 Dilute acid

Organic layer Acidic aqueous layer

Neutral & weakly basic alkaloids Salts of strongly basic alkaloids
& 1 NH4OH or Na2CO3
Non-alkaloidal impurities 2 CHCl3

Organic layer Basic aqueous layer

Strongly basic alkaloids Quaternary
ammonium bases
 GRADIENT PH EXTRACTION:
• This method is suitable for separating alkaloids of different
basicity (weakly, moderately and strongly basic).
• The crude mixture is dissolved in 2% tartaric acid and
extracted with organic solvent(like benzene) so the first
fraction contains neutral and/or very weakly basic alkaloids.
• The pH of the aqueous solution is gradually increased to pH
9 and extraction, after each increment of pH with organic
solvent.
• By this way different basicity are extracted.
• Strongly basic alkaloids are extracted at the end.
 OTHER METHODS

1) Direct crystallization from solvent

2) Steam distillation
3) Chromatographic techniques
GENERAL PHARMACOLOGIC ACTION OF A LKALOIDS:

 Analgesic (morphine, codeine)

 Narcotics (strychnine, brucine which are central
stimulant)
 Mydriatics (atropine)

 Miotics (physostigmine, pilocarpine)

 Ephedrine (rises in blood pressure)

 Reserpine (produce fall in excessive

hypertension)
BELLADONNA- TROPANE ALKALOID
 BELLADONNA

 “Bella-donna” is an Italian phrase meaning “beautiful

lady.” This name was given to the plant because the ladies
of Venice used Atropa Belladonna as a cosmetic (due to the
mydriasis effect).

SYNONYMS:Belladonna leaf, Belladonna herb, deadly

nightshade (European belladonna)
BIOLOGICAL SOURCE:
It consists of dried leaves and other aerial parts of atropa
belladonna Linn. FAMILY: solanaceae
GEOGRAPHICAL SOURCE:
England, Europe. In india, it is found in the
western himalayas from simla to kasmir &
adjoining areas of Himachal Pradesh.
Chemical Constituents :
➢ The total alkaloidal content of drug is 0.4 to 1%
& varies in different parts of plant roots (0.6),
stems (0.05%), leaves (0.4%), unripe & ripe
berries (0.19-0.21%) & seeds (0.33%).
➢ The main alkaloids are l-hyoscyamine & its
racemic form atropine.
➢ The drug also contains belladonine, scopoletin,
hyoscine, pyridine & N-methyl pyrroline.
➢ The later two are the volatile bases.
Theraputic uses of Belladonna:
➢ Belladonna is used as parasympatholytic drug with
anticholinergic properties.
➢ Used to reduce the secretion such as sweat, saliva and
gastric juice.
➢ It reduce spasm in case of intestinal gripping due to
strong pergatives.
➢ Act as antidote in opium and chloral hydrate poisioning.

Adulterants & substitutes

 It adulterated with leaves of phytolacca americana,

solanum nigrum & ailanthus glandulosa. Each of them
is distiguished by their histological character.
Marketed preparation of Belladonna
VINCA
- Indole Alkaloid
VINCA
Synonyms:- Vinca rosea, Catharanthus,
Madagascar, periwinkle & Barmasi.

Biological Source:- Vinca is the dried

entire plant of Catharanthus roseus
Linn. belonging to family Apocynaceae

Geographical Source:- The plant is a

native of Madagascar and is found in
many tropical and subtropical countries
especially in India, Australia, South
Africa and North and South America.
The plant is cultivated as garden plant
in Europe and India.
Leaves:- Green in colour

Flowers:-are either violet, pinkish

white or carmine red .

Root:- Pale grey in colour

Flowers:- Hermaphrodite (have both

male and female organs) and are
pollinated by bees.

Fruit:-follicles with numerous black

seeds.
- leaves and roots contain more alkaloids.

-About 90 alkaloids have been isolated from Vinca

- Ajmalicine, Serpentine are also present in other species of Apocynaceae.

- The important alkaloids in Catharanthus are

- the dimer indole indoline alkaloids Vinblastine and Vincristine
- they possess anticancer activity.
-Vindoline and Catharanthine are indole monomeric alkaloids.
- It also contains monoterpenes, sesquiterpene, indole and indoline
glycoside.
Vinblastine Vincristine
❑ Vinblastin is an antitumour alkaloid used in the treatment of
Hodgkin’s
disease

❑Vincristine is used to treat leukaemia in children

❑It may also be used as a gargle

❑ The flowers of the Periwinkle are gently purgative

❑It is stated, is excellent as a gentle laxative for children

Marketed preparation of vinca
RAUWOLFIA
- Indole Alkaloid
RAUWOLFIA
Synonyms:- Rauwolfia root , serpentina
root, Chhotachand

Biological Source:- Rauwolfia consist of

dried roots of the plant known as
Rauwolfia serpentina Benth, belonging
to family Apocynaceae.

Geographical Source:- They are found

distributed in the tropical regions of
Asia, America and Africa. Commercially
it is produced in india, sri lanka,
Myanmar, Thailand and america. In
india, it is cultivated in Utter Pradesh,
Bihar, Orissa, Tamil Nadu, West Bengal,
Karnataka, Maharastra, and Gujarat.
❖Macroscopic character:-
➢Leaves:- Simple, opposite, leaves are
arranged in whorls of 3 to 4,to 10 cm
long and 5 cm broad.

➢Fruits:- Round, 5 cm in diameter,

dark, purple or blackish when ripe.

➢Flower:- Glabrous, white or pinkish,

with deep red peduncle.

➢Medicinally Important parts:- Roots

and leaves.

➢Flowering time:- March to May in

Indian and Nepalese conditions.
Chemical Constituents:-

The major chemical constituents are:-

❖ Serpentine
❖ Reserpine
❖ Ajmaline
❖ Ajmalicine
❖ Ricinnamine
❖ Fatty acids
❖ Unsaturated alcohol
❖ Fumaric acid
THERAPEUTIC USES:-
➢ As anti-hypertensives
➢ In bowel disorder

➢ During fever

➢ Constipation

➢ Joint pain

➢ Hypnotic

➢ As sedatives properties

➢ As tranquilizer
PHARMACOLOGICAL ACTION:-

❖ Reserpine is used to treat mild to moderate

hypertension.

❖ These are normally involved in controlling heart rate,

force of contraction and peripheral resistance.

❖ Theeffects of reserpine include respiratory inhibition,

stimulation of peristalsis ,relaxation of membranes
and influence on the temperature regulating centre.
ETHNOMEDICAL USES:-
➢ As the antidote against the bites of venomous
reptiles, insect and animal bites.
➢ Used in the anxiety states.

➢ Traditionally being used in the intestinal disorder.

➢ Young shoot extract of serpentina is given three
times daily to cure pneumonia in early stage by the
people of Jhapa district (Nepal).
➢ Local people uses R.serpentina fresh leaves juices to
prevent eye inflammation.
DOSAGE:-

➢ Rauvolfia:- 100 to 150 mg (oral twice a day)

➢ Reserpine:- Initial dose 250 µg once a day

➢ Root powder:- 1-2 gm daily

AYURVEDIC PREPARATIONS:-
Sarpagandha ghanavati

Sarpagandha yoga

Sarpagandha churna

Mahesvari vati
Opium
- Isoquinazoline Alkaloid
Opium Alkaloids
Biological source : Opium is the air-dried milky exudate, or latex,
obtained by incising the unripe capsules of the opium poppy
Papaver somniferum (Papaveraceae).
For opium production, the ripening capsules, which are just
changing color from blue- green to yellow, are carefully incised with
a knife to open the latex tubes.
Although the ripe poppy capsule can contain up to 0.5% total
alkaloids, opium represents a much concentrated form and up to
25% of its mass is composed of alkaloids ( more than 40 alkaloids
were identified).
Historical overview of opium
1-Opium in ancient Egypt :
The plant was known in Europe at least 4000 years ago, as
evidenced by fossil remains of poppy seed cake and poppy
pods found in the Swiss lake dwellings of the Neolithic
Age. Opium was probably consumed by the ancient
Egyptians and was known to the Greeks as well.
2- Opium wars:
The continuing illegal export of opium to China by the British
triggered a two-phase war, aptly called the Opium Wars, between
1839 and 1842.
They concluded with China being forced to accept opium and
endurea growing addiction rate.
CHEMISTRY OF ALKALOID :
Opium alkaloids usually occur naturally combined with a
specific acid: (Meconic acid).
■ Meconic acid present only in Opium withmorphine.

■Meconic acid gives a deep purplish red-colored complex

with FeCl3.

■ClassificationofOpiumAlkaloids
1.Benzylisoquinoline Alkaloids : Papaverine ,
Narcotine
2.Phenylethylamine Alka loids: Narceine
3.Phenanthrene Alkaloids: Morphine , Codeine,
Thebaine
4. Protopine: Cryptopine
Isolation of the major opium alkaloids Principle:
1Morphine (phenolic), codeine (water soluble) and narceine (-
COOH) are solublein NaOH.
2 Inpresence of NaOH, only codeine can be extracted by CHCl3.
3 Narceine dissolved in NH4OH (-COOH) leaving morphine
insoluble inNH4OH.
4. Papaverine, narcotine and thebaine are insoluble in NaOH.

5. Thebaine acetate is water soluble salt while papverine

and narcotine acetate salts are insoluble in water.

6. Narcotine oxalate salt is water soluble while

papaverine oxalate salt is insoluble in water.
 Therapeutic uses of opium
1-treating medicines as :
a- pain killer analgesics ex.Morphine.
b- cough suppressants ex. codeine and Noscapine.
c- smooth muscle relaxant ex. Papaverine
2- leading compounds for modelling of semi-synthetic and
totally synthetic
a-analgesics
b- cough suppressants
3- abused drugs.
4- sleep-inducer (narcotic)
5- Morphine named after Morpheus the god of dreams (Greek
Mythology)