1. Shri D.D. Vispute College of Pharmacy and Research Center,Panvel
www.visputepharmacy.in
Alkaloids
DR. CHANCHAL RAJ

2. Contents
 Inttroduction
 Definition
 Properties
 Classification
 Extraction-general methods
 Study of Drugs : Ephedra, colchicum, Datura, Coca, Ashwagandha, Rauwolfia, Vinca, Ergot,
Kurchi, Vasaka, Opium, Ipecac, Berberis aristata, cinchona, Pepper, Tobacco, Tea, Coffee,
Cocoa, Pilocarpus, Solanum
 Isolation, Identification and Analysis of Phytoconstituents: Piperine, Caffeine
 Marketed products and therapeutic uses of Atropine, Pilocarpine, Vasaka, Kurchi, Ephedra,
Pepper

3. Introduction
 Alkaloids are a group of basic naturally occurring organic compounds containing at least one
nitrogen atom.
 Alkaloids meaning alkali like.
 The term “alkaloids” in German “Alkaloide” was introduced in 1819 by the German chemist
Friedrich Wilhelm Meissner.
 These are produced by large variety of organisms viz. bacteria, fungi, plants and animals.
 In plants alkaloids are found as secondary metabolites groups.
 More than 10,000 different alkaloids have been discovered in species from over 300 plant
families.
 These compounds are renowned for their potent pharmacological activities.

4. Definition: Alkaloids are a group of basic, naturally occurring organic
compounds that contain at least one nitrogen atom present in heterocyclic
ring and which shows pharmacological effects on humans and/or animals
when used in small quantities.
Occurrence:
 In dicotyledonous families like apocynaceae, solanaceae, rubiaceae,
rutaceae, papavaraceae, papileonaceae.
 Absent in labiatae, rosaceae.
 Found in monocotyledonous families viz. liliaceae, amaryllidaceae.
Functions in plants:
 As reservoirs for protein synthesis.
 Protects plants from herbivores and insects.
 End products of detoxification mechanisms.

5. Properties
Physical properties
 Most alkaloids are well-defined crystalline substances which unite with acids to form salts.
 In the plant they may exist in the free state, as salts or as N-oxides.
 In addition to the elements carbon, hydrogen and nitrogen, most alkaloids contain oxygen.
 Coniine from hemlock and nicotine from tobacco, are oxygen-free and are liquids.
 Generally alkaloids are colourless. Exception: berberine is yellow and the salts of
are copper-red.
 Bitter in taste.
 Solubility: Alkaloidal salts are soluble in polar solvents and insoluble in organic solvents.
Alkaloidal bases are soluble in organic solvents and insoluble in polar solvents.

6. Chemical properties:
 Alkaloids in plants, due to its basic nature; generally exists as salts of organic acids like oxalic
acids, acetic acid, citric acids, malic acid, tannic acid, lactic acid and tartaric acids.
 Opium alkaloids like morphine are found in the salts form of meconic acid.
 Cinchona alkaloids are found with quinic acid.
 Nicotine and narceine are found in free in nature.
 Few alkaloids like of solanum occur as glycosides of sugars like glucose, rhamnose and
galactose.
 Most of the alkaloids contain one or more nitrogen in the tertiary state in a ring system.

7. General methods of extraction
 Extraction methods vary with the scale and purpose of the operation, and with the raw material.
 For many research purposes chromatography gives both speedy and accurate results.
 However, if an appreciable quantity of alkaloid is required, one of the following general methods will usually serve.
Process A.
 The powdered material is moistened with water and mixed with lime which combines with acids, tannins and other
phenolic substances and sets free the alkaloids (if they exist in the plant as salts).
 Extraction is then carried out with organic solvents such as ether or petroleum spirit.
 The concentrated organic liquid is then shaken with aqueous acid and allowed to separate.
 Alkaloid salts are now in the aqueous liquid, while many impurities remain behind in the organic liquid.
Process B.
 The powdered material is extracted with water or aqueous alcohol containing dilute acid.
 Pigments and other unwanted materials are removed by shaking with chloroform or other organic solvents.
 The free alkaloids are then precipitated by the addition of excess sodium bicarbonate or ammonia and separated
filtration or by extraction with organic solvents.
 Volatile liquid alkaloids (nicotine and coniine) are isolated by distillation.
 The powdered material that contains alkaloids is extracted with water and the aqueous extract is made alkaline
sodium carbonate or ammonia and the alkaloid is distilled off in steam.
 This could be collected and purified.

8. Classification
 Alkaloids show great variety in their botanical and biochemical origin, in chemical structure
and in pharmacological action.
 Hence many different systems of classification are possible for alkaloids.
1. Simple classification
2. Biosynthetic classification
3. Pharmacological classification
4. Taxonomic classification
5. Chemical classification
 Based on chemical structure alkaloids are broadly classified into two divisions
I. Non-heterocyclic or atypical alkaloids, sometimes called ‘protoalkaloids’ or biological
amines.
II. Heterocyclic or typical alkaloids, divided into 14 groups according to their ring

9. I. Non-heterocyclic or atypical alkaloids: contain nitrogen in aliphatic chain.
Protoalkaloids or Biological amines:
 Protoalkaloids are compounds, in which the N atom derived from an amino acid is not a
of the heterocyclic ring.
 Such kinds of alkaloid include compounds derived from L-tyrosine and L-tryptophan.
 Protoalkaloids are those with a closed ring, being perfect but structurally simple alkaloids.
 They form a minority of all alkaloids. Hordenine, mescaline and yohimbine are good
of these kinds of alkaloid.
 These alkaloids have a pyrroline nucleus.
Groups Example Source use
Phenyl ethylamine
alkaloid
Ephedrine, mescaline Ephedra sp. Asthma
Tropolone alkaloids Colchicine Colchicum sp. Gout

10. TRUE ALKALOIDS PROTO ALKALOIDS PSEUDOALKALOIDS
True alkaloids derive from amino
acid
Also derived from amino acid the basic carbon skeletons
not derived from amino acids
Nitrogen in
heterocyclic ring
Nitrogen not in heterocyclic ring Nitrogen in aliphatic ring
Highly
reactive substances with biological
activity even in low doses
Closed ring, being perfect but
structurally simple alkaloids
Pseudoalkaloids can be acetate
phenylalanine
derived or terpenoid, as well as
steroidal alkaloids
Precursors: L-ornithine, L-lysine, L-
phenylalanine/Ltyrosine,
L-tryptophan and L-histidine
Precurser: L-Tryptophan, L- Precursor: phenylalanine
Examples: cocaine,
quinine and morphine.
Ephedrine, colchicine and
mescaline
Caffeine, theobromine,
theophylline

11.  II. Heterocyclic or typical alkaloids, divided into 12 groups according to their ring structure.
Contain nitrogen in heterocyclic ring system.
 Alkaloidal Amines – Ephedra, colchicum
 Tropane - Datura, Coca, Ashwagandha
 Indole - Rauwolfia, Vinca, Ergot
 Steroidal –Kurchi
 Quinazoline – Vasaka
 Benzyl isoquinoline – Opium
 Isoquinoline - Ipecac, Berberis aristata
 Quinoline - cinchona
 Pyridine-Piperidine –Pepper, Tobacco
 Purine - Tea, Coffee, Cocoa
 Imidazole – Pilocarpus
 Glycoalkaloids- Solanum

12. Basic ring structure:

13. Alkaloidal amines: Ephedra and Colchicum
Colchicum
 Source: Colchicum consists of dried ripe seeds and corms of Colchicum
autumnale Linn., belonging to family Liliaceae.
 Chemistry: The active principle is said to be an alkaline substance of a very poisonous nature
called Colchicine.
 Also found to contain demecolcine, resin, called colchicoresin, fixed oil, glucose
and starch.
 Chemical Test: Colchicum corm with sulphuric acid (70%) or conc.HCl produces yellow colour
due to the presence of colchicines.
 Uses: Both the corm and the seeds are analgesic, antirheumatic, cathartic and emetic. They are
used mainly in the treatment of gout and rheumatic complaints, usually accompanied with an
alkaline diuretic. Leukaemia has been successfully treated with autumn crocus, and the plant
has also been used with some success to treat Bechet’s syndrome, a chronic disease marked by
recurring ulcers and leukaemia. A very toxic plant, it should not be prescribed for pregnant
women or patients with kidney disease, and should only be used under the supervision of a
qualified practitioner.

15. Tropane - Datura, Coca, Ashwagandha
Datura
 Source: Datura herb consists of the dried leaves and flowering tops of Datura metel
Linn and Datura metel var. fastuosa belonging to family Solanaceae.
 Chemistry: Datura herb contains up to 0.5% of total alkaloids. hyoscine (scopolamine)
is the main alkaloid, while l-hyoscyamine (scopoline) and atropine are present in very
less quantities.
 Chemical Tests 1. Vitali-Morin test: The tropane alkaloid is treated with fuming nitric
acid, followed by evaporation to dryness and addition of methanolic potassium
hydroxide solution to an acetone solution of nitrated residue. Violet colouration takes
place due to tropane derivative.
 2. On addition of silver nitrate solution to solution of hyoscine hydrobromide,
yellowish white precipitate is formed, which is insoluble in nitric acid, but soluble in
dilute ammonia.
 Uses: In Ayurveda black datura is considered more efficacious or more toxic. D. metel
is used in the manufacture of Hyoscine or scopolamine. It exhibits parasympatholytic
with anticholinergic and CNS depressant effects. The drug is used in cerebral
excitement, asthma and in cough.

16. Datura metel

17. Coca:
 Source: Coca consists of the dried leaves of various species of Erythmxylon, that is,
Erythroxylon coca Lam (Huanco or Bolivian coca) or Erythroxylon coca var. Spruceanum
(Peruvian, Truxillo or Java coca) also known as Erythroxylon truxillense Rusby., belonging to
family Erythroxylaceae.
 Chemistry: Coca leaves contain the alkaloids Cocaine, Annamyl Cocaine, and Truxilline or
Cocamine. Truxillo or Peruvian leaves contain more alkaloid than the Bolivian, though the
latter are preferred for medicinal purposes. Java Coca contains tropacocaine and four yellow
crystalline glucosides in addition to the other constituents.
 Uses: The actions of Coca depend principally on the alkaloid Cocaine. Cocaine has stimulant
action on CNS. The leaves are extensively chewed to relieve hunger and fatigue. Coca
alkaloids cause also hallucination. Coca leaves are used as a cerebral and muscle stimulant,
especially during convalescence, to relieve nausea, vomiting and pains of the stomach without
upsetting the digestion. Cocaine also has local anesthetic action on skin and mucous
membrane; and is used as dental anaesthesia and minor local surgery of ophthalmic, ear,
nose and throat.
 Adulterant: Jaborandi leaves are used as an adulterant of Coca leaves.

18. Erythroxylon coca

19. Ashwagandha : Withania
 Source: It consists of the dried roots and stem bases of Withania somnifera Dunal, belonging
to family Solanaceae.
 Chemistry: The plants contain the alkaloid withanine as the main constituent and somniferine,
pseudowithanine, tropine and pseudotropine, hygrine, isopellederine, anaferine. The leaves
contain steroid lactone, commonly known as withanolides.
 Uses: To treat nervous disorders, intestinal infections and leprosy. Ashwagandha is one of the
most widespread tranquillizers used. Also used as an adaptogen and having a rejuvenative
effect on the body, improve vitality and aid recovery after chronic illness.

20. Chemical structure: Withania somnifera

21. Indole alkaloids: Rauwolfia, Vinca, Ergot
Rauwolfia : Sarpagandha
 Source: Rauwolfia consists of dried roots of Rauwolfia serpentine Benth., belonging to family
Apocynaceae.
 Chemistry: Rauwolfia contains about 0.7–2.4% total alkaloidal bases from which more than 80
alkaloids have been isolated. The prominent alkaloids isolated from the drug are reserpine,
rescinnamine, rescidine, raubescine and deserpidine. The other alkaloidal components are
ajmalinine, ajmaline, ajmalicine (8-yohimbine), serpentine, serpentinine, tetrahydroreserpine,
raubasine, reserpinine, isoajamaline and yohambinine.
 Uses: Rauwolfia in used as hypnotic, sedative and antihypertensive. It is specific for insanity,
reduces blood pressure. It is given in labours to increase uterine contractions and in certain
neuropsychiatric disorders. Ajmaline, which has pharmacological properties similar to those of
quinidine, is marketed in Japan for the treatment of cardiac arrhythmias.

23. Vinca: catharanthus
 Source: Vinca is the dried entire plant of Catharanthus roseus Linn., belonging
to family Apocynaceae.
 Chemistry: Alkaloids are present in entire shrub but leaves and roots contain
more alkaloids. About 90 alkaloids have been isolated from Vinca from which
some like Ajmalicine, Serpentine and Tetrahydroalstonine are known and are
present in other species of Apocynaceae. The important alkaloids are the
indole indoline, Vinblastine and Vincristine and they possess definite
activity. Vindoline and Catharanthine are indole monomeric alkaloids. It also
contains monoterpenes, sesquiterpene, indole and indoline glycoside.
 Uses: Vinblastin is an antitumour alkaloid used in the treatment of Hodgkin’s
disease. Vincristine is a cytotoxic compound and used to treat leukaemia in
children. Vinca is used in herbal practice for its astringent and tonic properties
in menorrhagia and in haemorrhages generally. In cases of scurvy and for
relaxed sore throat and inflamed tonsils, it may also be used as a gargle.

24. Catharanthus roseus

25. Ergot: Ergot of Rye
 Source: Ergot is the dried sclerotium of a fungus, Claviceps purpurea Tulasne, belonging to
family Clavicipitaceae, developing in the ovary of rye plant, Secale cereale (Family Poaceae).
 Chemistry: A large number of alkaloids have been isolated from the Ergot. The most important
alkaloids are ergonovine and ergotamine.
On the basis of solubility in water the alkaloids are divided into two groups: water-soluble
Ergometrine (or ergonovine) group or water-insoluble (ergotamine and ergotoxine)
groups.
Group Alkaloids
Water - soluble group
I. Ergometrine group Ergometrine, Ergometrinine
Water – insoluble group
II. Ergotamine group Ergotamine, Ergotaminine, Ergosine, Ergosinine
III. Ergotoxine group Ergocristine, Ergocryptine, ergocristinine,
ergocryptinine

26. Ergot
Ergocrystine
Ergotamine

27. Cultivation and Collection
The life cycle of the fungus, Claviceps purpurea, which is a parasite, passes through the following characteristic
stages:
1. Sphacelia or honeydew or asexual stage
2. Sclerotium or ascigerous or sexual stage and
3. Ascospore stage.
1. Sphacelia or honeydew or asexual stage
The rye plant becomes infected by the spores of the fungus in the spring session when flowers bloom for
one week. The spores are carried by the wind or by insects to the flowers and collected at the base of the
ovary where moisture is present.
There germination of the spores takes place. A filamentous hyphae is formed which enters into the wall of
ovary by enzymatic action. A soft, white mass over the surface of ovary is formed, which
is known as Sphacelia. A sweet viscous yellowish liquid, known as honeydew, is secreted during the Sphacelia
stage which contains reducing sugars (reduce Fehling solution).
From the ends of some hyphae small oval conidiospores (asexual spore/s) are abstricted which remain
suspended on honeydew. The sweet taste of honeydew attracts some insects like ants and weevils. Insects
the sweet liquid and carry the conidiospores to the plants and spread the
fungal infection in the rye plants. Cultured conidiospores are used for the inoculum. Strains capable of
producing about 0.35% of selected alkaloids, mainly ergotamine, are now utilized.

28. 2. Sclerotium or ascigerous or sexual stage
 During the Sphacelia stage the hyphae enter only the outer wall of the ovary.
 On further development they penetrate into deeper parts, feed on the ovarian tissues and
replace it by a compact, dark purple hard tissue known as pseudoparenchyma.
 It forms the sclerotium or resting state of the fungus. During summer the sclerotium or ergot
increases in size and projects on the rye, showing sphacelial remains at its apex.
 It is collected at this stage by hands or machine and used as a drug.
 Ergot is then dried to remove moisture.
 About 6 weeks after inoculation, the mature sclerotia are harvested. They may be picked up by
hand or collected by machine.
 The number and size of the ergots produced on each spike of cereal by C. purpurea varies, rye
usually bears sclerotia, while wheat bears very few.

29. 3. Ascospore stage
 If Ergot is not collected, it falls on the ground.
 In the next spring session they produce stalked projections known as stromata which have globular
heads.
 In the inner surface of the heads there are many flask-shaped pockets known as perithecia.
 Each of these perithecia contains many sacs (asci) which possesses eight of the thread-like
ascospores.
 These ascospores are carried out by insects or wind to the flowers of the rye as described in the
stage.
 In this way life cycle of Ergot is completed.
 The ascospores may be germinated on a nutritive medium to get conidiospore bearing cultures.
 The suspension of these conidiospores is usually used as a spray to infect rye plants for commercial
production of Ergot.
 Ergot is collected from fields of rye when the sclerotia are fully developed and projecting from the
spike, or they are removed from the grain by shifting.
 The size of the crop varies according to weather conditions.
 The vegetative phase of the fungus can, like that of other moulds, be cultivated artificially.
 Under such conditions the typical sclerotia do not develop.

30. Ergot life cycle

31. Uses
 Ergot is oxytocic, vasoconstrictor and abortifacient and used to assist delivery and to reduce
post-partum haemorrhage.
 Lysergic acid diethylamide (LSD-25), obtained by partial synthesis from lysergic acid, is a
potent specific psychotomimetic.
 Ergometrine is oxytocic and used in delivery.
 It stimulates the tone of uterine muscles and prevents postpartum haemorrhage.
 Only ergometrine produces an oxytocic effect, ergotoxine and ergotamine having quite a
different action.
 Ergometrine is soluble in water or in dilute alcohol. It is known as ergonovine.
 Ergotamine and the semisynthetic dihydroergotamine salts are used as specific analgesics for
the treatment of migraine.
 Lysergic acid diethylamide (LSD-25), prepared by partial synthesis from lysergic acid, is a
potent specific psychotomimetic.

32. Chemical Tests
1. Ergot under UV light shows a red-coloured fluorescence.
2. Ergot powder is extracted with a mixture of CHCl3 and sodium carbonate.
The CHCl3 layer is separated and a mixture of p-dimethylaminobenzaldehyde (0.1 g), H2SO4
v/v, 100 ml) and 5% ferric chloride (1.5 ml) is added. A deep blue colour is produced.