An introduction to alkaloids by Dr. Preeti Verma

Prepared by,
Dr. Preeti D. Verma
Asst. Professor, Department of Pharmacognosy
L. M. College of Pharmacy, AhmedabadAhmedabad..
AN INTRODUCTIONAN INTRODUCTIONAN INTRODUCTIONAN INTRODUCTION
TO ALKALOIDSTO ALKALOIDS

CONTENTS
Definition
Distribution
Properties
Chemical tests
Classification
Role of alkaloids
Isolation
Occurrence
Dr. Preeti D. Verma, L. M. C. P.

Glimpses of some known plants
drugs containing alkaloids as their
active constituent

DEFINITION
Alkaloids are defined as:
 Basic organic substances,
 Which contain one or more nitrogen
atoms in a heterocyclic ring or in the
side chain
 And have significant physiological
action in man and animals,
 When given in very small quantities.
 They are mostly derived from Amino
Acids. Dr. Preeti D. Verma, L. M. C. P.

1. Animals:
DISTRIBUTION
2. Bacteria:
47% species of bacteria contain alkaloid
e.g. Pyocyanine from Pseudomonas aeruginosa
Castoramine
from Canadian
beaver
Muscopyridine from Muskdeer

3. Plants:
Out of 60 different orders in higher plants, 34 orders
contain alkaloids.
Lower plant, e.g. Ergotamine, Ergometrine from
Ergot (fungus)
Gymnosperm, e.g. Taxus
Pteridophyte, e.g. Ephedra
Angiosperm

ANGIOSPERM
Monocot
Liliaceae, e.g. Colchicum
Dicot
1) Apocynaceae, e.g. Rauwolfia, Vinca
2) Solanaceae, e.g. Belladonna, Datura,
Ashwagandha
3) Leguminosae, e.g. Physostigma
4) Rutaceae, e.g. Pilocarpus
5) Berberidaceae , e.g. Berberis
6) Loganiaceae, e.g. Nux vomica
7) Menispermaceae, e.g. Curare
8) Papaveraceae, e.g. Opium
9) Ranunculaceae, e.g. Aconite
10) Rubiaceae, e.g. Cinchona, Ipecac
11) Acanthaceae, e.g. Vasaka
12) Theaceae, e.g. Tea
13) Palmae, e.g. Areca
14) Campanulaceae, e.g. Lobelia

PLANT PART EXAMPLE
Root Rauwolfia, Belladonna, Ashwagandha, Ipecac
Bark Kurchi, Cinchona
Stem Ephedra
Leaves Lobelia, Vasaka, Datura, Hyoscyamus,
Belladonna
Fruit Conium
Seed Nux vomica, Colchicum, Areca, Physostigma,
Coffee
Poppy Opium
Entire plant Vinca
OCCURENCE

PROPERTIES
STATE & COLOR: Colorless, crystalline, non-volatile
solids.
Exception:
Some alkaloids are coloured.
E.g. Berberine, Colchicine - Yellow
Sanguinarine - Copper-red
Some are liquid and volatile in nature (oxygen free)
E.g. Nicotine, Coniine, Pilocarpine
TASTE: Bitter.
Physical Properties

Forms: Free base & Salt form.
SOLUBILITY:
Free bases:
Soluble in Organic solvents and Insoluble in water.
Salts:
Insoluble in Organic solvents and Soluble in water.

Exceptions:
E.g.
Colchicine (free base) is soluble in alkaline water, acid
or water.
Caffeine (free base) is freely soluble in water.
Quinine Sulphate (salt) is sparingly soluble in water
i.e. 1 part of quinine sulphate is soluble in 1000 parts of
water.
[Quinine HCl is readily soluble in water i.e. 1 part in
less than 1 part of water – complying to solubility
property]
22Dr. Preeti D. Verma, L. M. C. P.

OPTICAL ACTIVITY
As alkaloids contain at least one asymmetrical carbon
atom, they are optically active.
Usually laevorotatory
E.g.
 l-form of Hyoscyamine twice more active than
racemic form i.e. Atropine and it is 10-20 times
more active than d-form.
 l-form of ergotamine alkaloid are more active
than d-form.
 l-ephedrine is 3.5 times more active than
d-ephedrine.
Degree of rotation displayed is fixed characteristic
feature of particular alkaloid.Dr. Preeti D. Verma, L. M. C. P.

• Primary amines R-NH2 e.g. Norephedrine
• Secondary amines R2-NH e.g. Ephedrine, Colchicine
• Tertiary amines R3-N e.g. Atropine
• Quaternary
ammonium salts R4-N+ e.g d-Tubocurarine
Basicity:
Basic in reaction due to availability of lone pair of
electron on nitrogen
Alkaloid contain one or more number of nitrogen:
Chemical Properties

Primary amines, R-NH2
e.g. Norephedrine
Secondary amines, R2-NH
e.g. Ephedrine
Tertiary amines, R3-N
e.g. Atropine
Quaternary amines, R4-N+
e.g d-Tubocurarine

Basicity increased if the adjacent group is
electron releasing group.
Basicity decreases if the adjacent group is
electron withdrawing group.
R-NH2 > R2-NH > R3-N > R4-N+Basicity:
Electron withdrawing groups:
Halogens (F, Cl)
Nitriles (CN)
Carbonyls (CO)
Nitro groups (NO2)
Electron releasing group:
Alkyl groups
Alcohol groups
Amino group

Natural Forms:
Alkd exist – as free base (as amine), as salt with acid
or alkaloid N-oxide
N-oxide product of tertiary alkaloids are common and
can be easily prepared from original base.
They are pharmacologically active & have got
following properties.
 Delayed release properties
 Low toxicity
 Low addictive properties in comparison to the
corresponding organic bases
E.g. : Morphine N-oxide,
N-oxide of Hyoscyamine,
N-oxide of Strychnine,
N-oxide of Reserpine, etc.Dr. Preeti D. Verma, L. M. C. P.

Individual alkaloid gives colour or precipitate with
certain specific reagents.
Chemical Tests
Reagent Composition Precipitates
Dragendorff’s
reagent
Solution of Potassium
bismuth iodide
Reddish-orange
precipitates
Mayer’s
reageant
Potassium mercuric
iodide solution
Cream coloured
precipitates
Wagner’s
reagent
solution of Iodine in KI Reddish-orange
precipitates
Hager’s
reagent
Saturate solution of Picric
acid
Yellow precipitate

Vitali-morin test : For tropane alkaloid
Alkaloid + fuming HNO3 Evaporate to dryness
Add acetone & methanolic KOH solution Violet colour.
Colour test with Van-urk’s reagent (p-dimethyl amino
benzaldehyde): For Indole alkaloid
Bluish violet – red colour.
Colour test for Colchicine:
With Mineral acid Yellow colour.
Murexide test: For Purine alkaloids
Caffeine + KClO3 + HCl Evaporate to dryness
Expose residue to NH3 vapours Purple colour.
Thalleoquin test : For Quinine alkaloid
Powdered drug + Br2 water + Dilute NH3 solution
Emerald green colour.
Test for Opium: Due to Meconic acid
Opium+FeCl3 Deep Red Colour.Dr. Preeti D. Verma, L. M. C. P.

ALKALOID
Pharmacological
Taxonomical
Biosynthetic
Chemical
CLASSIFICATION OF ALKALOIDSCLASSIFICATION OF ALKALOIDS

I. CHEMICAL CLASSIFICATIONI. CHEMICAL CLASSIFICATION
True/Typical/Heterocyclic AlkaloidsTrue/Typical/Heterocyclic Alkaloids
Proto/Atypical/NonProto/Atypical/Non--heterocyclic Alkaloids/heterocyclic Alkaloids/
Biological amines/Amino AlkaloidsBiological amines/Amino Alkaloids
Pseudo alkaloid/False alkaloidsPseudo alkaloid/False alkaloids
Most accepted way of classification of alkaloid.
According to their molecular structure and biosynthetic
pathway from which they are formed in the plants.

ALKALOIDALKALOID
• True alkaloids
 Contain one or more nitrogen in heterocyclic ring
 Derived from amino acid

True alkaloid

ALKALOIDALKALOID
• True alkaloids
• Proto alkaloids
 Do not contain nitrogen in heterocyclic ring, but
in side-chain.

Ephedrine
Proto alkaloid

ALKALOIDALKALOID
• True alkaloids
• Proto alkaloids
 Do not contain nitrogen in heterocyclic ring, but
in side-chain.
• Pseudo alkaloids
 Contain nitrogen in heterocyclic ring
 Not derived from amino acid
 Give standard qualitative tests for alkaloids

Pseudo alkaloid

TRUE ALKALOIDSTRUE ALKALOIDS
Further classified into 13 classes:
1. Pyrrole and Pyrrolidine
E.g.: Hygrine (Coca)

2. Pyrrolizidine
E.g.:
Echimidine (Russian Comphrey)
Senecionine (Senecio)

3. Pyridine and Piperidine
E.g.:
Arecoline (Areca)
Lobeline (Lobelia)

4. Tropane
E.g.:
Atropine (Datura, Belladonna, Hyoscyamus)
Hyoscine
Cocaine (Erythroxylum)

5. Quinoline
E.g.:
Quinine (Cinchona)
Quinidine
Cinchonine

6. Isoquinoline
E.g.:
Papaverine (Opium)
Emetine (Ipecac)
Cephaeline (Ipecac)

7. Quinazoline
E.g.:
Vasicine (Vasaka )

8. Phenanthrene
E.g.:
Morphine (Opium)

9. Indole
E.g.:
Vincristine (Vinca)
Reserpine (Rauwolfia)
Strychnine (Nux vomica)
Physostigmine (Physostigma)
Ergotamine, Ergometrine (Ergot)Dr. Preeti D. Verma, L. M. C. P.

10. Indolizidine
E.g.:
Castenospermine (Castenospermum)

11. Imidazole/Glyoxaline
E.g.:
Pilocarpine (Pilocarpus)

12. Aporphine
E.g.:
Boldine (Boldo tree)
N-CH3

13. Norlupinane
E.g.:
Lupanine (Cytisus)

PROTO ALKALOIDSPROTO ALKALOIDS
Examples:
 Ephedrine
 Colchicine Ephedrine

PSEUDO ALKALOIDSPSEUDO ALKALOIDS
Further classified into 3 classes:
E.g.
Caffeine (Tea, Coffee, Cola)
Theophylline
1. Purine1. Purine

2. Steroidal2. Steroidal
E.g.:
Conessine (Kurchi)
Protoveratrine (Veratrum)
Solasodine (Solanum)

3. Terpenoidal3. Terpenoidal
E.g.:
Aconitine (Aconite)
Units of Isoprene (C5H8)

Sr. No. Types of
Alkaloid
Basic Ring
Structure
Examples Source
True Alkaloid
1 Pyrrole and
Pyrrolidine
Hygrine Coca
2
3…..
till 13
Proto alkaloids
Pseudo alkaloids
1
2
3
N
H
N
H
CLASS ASSIGNMENT
Prepare a summary of all types of alkaloids in tabular form as shown below:

PHARMACOLOGICAL CLASSIFICATION
Based on their biological action & therapeutic use.
USE EXAMPLE
Anticholinergic Belladonna, Datura, Hyoscyamus
Cholinergic Physostigma, Pilocarpus
Anticancer Vinca
Antimalarial Cinchona
Anti-arrythmic Cinchona
CNS Stimulant Nux vomica, Tea, Coffee, Ephedrine
Antiamoebic Kurchi, Ipecac
Respiratory stimulant Lobelia, Ephedra
Narcotic Analgesic Opium
Expectorant Vasaka, Ipecac
Sympathomimetic Ephedrine
Anti-gout Colchicum

TAXONOMICAL CLASSIFICATION
Based on their distribution in various plant families.
 It is based on their distribution in various plant
families.
E.g. :
Solanaceous alkaloid – Tropane alkaloids.
 They grouped as per the name of the genus in which
they occur.
E.g. :
Ephedra – Ephedrine
Atropa – Atropine
Ergot – Ergotamine, Ergometrine
Colchicum - Colchicine
Cinchona – Quinine, CinchonineDr. Preeti D. Verma, L. M. C. P.

Based on their precursors from which the alkaloids are
biosynthesized in the plant i.e. amino-acid precursor.
BIOSYNTHETIC CLASSIFICATION
AMINOACID ALKALOID
Tryptophan Ergot alkaloid, Reserpine, Vincristine,
Quinine & Physostigmine.
Ornithine Tropane alkaloid, Pyrrolidine alkaloid,
Pyrrolizidine alkaloid
Phenyl alanine Ephedrine
Tyrosine Opium alkaloid, Ipecac alkaloid,
Colchicine
Lysine Piperidine alkaloid

Reserve substance with an ability to supply nitrogen
Defensive mechanism for plant growing in dry
regions to protect from grazing animals, herbivores
and insects
End product of detoxification mechanism in plant.
Regulatory growth factors in plant.
Present normally in conjugation with plant acid like
meconic acid, cinchotannic acid. So, act as carrier for
transportation of such acids in plant.
ROLE OF ALKALOID IN PLANTS

The alkaloids are poisonous in nature, but when
used in small quantity they exert useful
physiological effect. So, they have secured significant
place in medicine.
ROLE OF ALKALOID IN HUMAN

SaltSalt BaseBase
AcidAcid
BaseBase
Aqueous SolventAqueous Solvent Organic SolventOrganic Solvent
isolationisolation

Powdered material
Moisten with water containing lime
(Combines with Acids & Set free the alkaloidal base)
Extract with Organic solvent, like ether
Concentrate the organic extract
Shake concentrate with aqueous acid and allow to separate
The aqueous liquid contain alkaloidal salt.
Method – A (Salts)

Method – B (Free base)
Powdered material
Extract with water or aqueous alcohol containing dilute acid
Shake with Chloroform or other Organic solvent
Aqueous layer
(Contain alkaloidal salt)
Organic layer
(pigments and unwanted
materials)
Discard it
Add excess of NH3
(Free alkaloidal base
Precipitated)
Separated ppts by filtation or extraction with organic solventDr. Preeti D. Verma, L. M. C. P.

Aqueous extract
Make alkaline with Caustic Soda or Sodium carbonate
Alkaloid is distilled off in Steam
Method – C (Liquid)

PURIFICATION
1. Direct crystallization from solvent :
 Simple method of purification
 Alkaloids are crystallised in form of salts such as
oxalate, picrate or tartrate.
 May not be useful in case of complex mixtures
2. Steam distillation :
 Esp. employed for volatile liquid alkaloid, like
Nicotine, Coniine.
3. Chromatographic technique :
 Ideal for separation for vast number of plant alkaloids
 The different techniques of chromatography, like TLC,
Column, GC, HPLC, HPTLC, etc. are used for
separation of individual alkaloids from complex
mixtures. Dr. Preeti D. Verma, L. M. C. P.

4. Gradient pH technique :
 Variations in the extent of basicity of different alkaloids
Crude alkaloidal mixture
Dissolve in 2% tartaric acid solution
Extract with benzene
This fraction contains neutral and/or very weakly basic alkaloids
pH of solution is increased gradually by 0.5 up to pH 9
Extraction is carried out at each pH level with organic solvent
By this way, the alkaloids with different basicity are extracted
Strongly basic alkaloids are extracted at the end

 Trease and Evans, Pharmacognosy, 15th edition, 2002.
 Sim Stephen K, Medicinal Plant Alkaloids, 1969.
 Manske, The Alkaloids – Chemistry and Physiology,
1950.
 Trevor Robinson, The Organic Constituents of Higher
Plants, 1964.
 Shah and Quadry, Pharmacognosy, 12th edition,
Revised 2004-05.
 Tyler and Brady, Pharmacognosy, 8th edition.
 C.K.Kokate, Pharmacognosy, 19th edition, 2002.
 S.V. Bhat, Chemistry of Natural products, Reprint 2005.
References

An introduction to alkaloids by Dr. Preeti Verma

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