ALKALOIDS

DR. MANASI GHOLKAR

ASSISTANT PROFESSOR
DEPARTMENT OF PHARMACOGNOSY,

ORIENTAL COLLEGE OF PHARMACY

GENERAL INTRODUCTION

• Nitrogen containing compounds

• ‘Alkaloid’ coined by Meissner, German pharmacist
• Used for various purposes like poisons, medicines, poultices, teas, etc
• Some of the alkaloids isolated in the earlier era were morphine, emetine, colchicine,
cinchonine, strychnine, brucine and piperine
• Currently more than 6000 alkaloids have been isolated
 DEFINITION

• Alkali-like (resemble some characters of naturally occurring complex amines)

• Organic products of natural or synthetic origin which are basic in nature and contain one or more
nitrogen atoms, normally or heterocyclic nature and possess specific physiological actions on the human
or animal body, when used in small quantities-TRUE ALKALOIDS

• ‘Proto’ OR ‘Amino’ Alkaloids- simple amines, N not in heterocyclic ring eg. Mescaline, ephedrine,
colchicine, N,N-dimethyl tryptamine
• ‘Pseudoalkaloids’- steroidal, terpenoidal and purines; not derived from amino acids eg. Conessine, caffeine
PROPERTIES

• Most alkaloids are crystalline solids

• (exception nicotine [Volatile in nature], Lobeline and coniine are liquid in
nature )

• Most alkaloids are colourless in nature exception berberine is yellow

FUNCTIONS IN PLANTS

Protective against insects and herbivores due to their bitterness and toxicity.

Help in detoxification : final product of metabolism(waste products).

Source of energy in case of deficiency in carbon dioxide assimilation.

Source of nitrogen in case of nitrogen deficiency.

Growth regulators in certain metabolic systems.

EFFECTS IN HUMANS

Highly potent in nature

Produce varying degrees of physiological and psychological responses
In large doses - highly toxic - fatal
In small doses, many have therapeutic value
muscle relaxants, tranquilizers, pain killers, mind altering drugs,
chemotherapy
ISOLATION AND EXTRACTION

Solubility:
In plant they are present as either free bases or as salts in combination
with plant acids
Free bases are soluble in organic solvents
Alkaloidal salts are soluble in water
ISOLATION AND EXTRACTION

• Based on its basic nature and solubility

• Alkaloids usually in salt form in plants🡪 treatment with a base 🡪

conversion of salt to base form 🡪 separation of free base using an organic
solvent [STAS OTTO PROCESS]
ISOLATION PROCESS

• Plant defatting (seed and leaf)

Step 1 • Solvent: Petroleum ether (*alkaloid should not be soluble)

• * Soluble drug: pretreated with acid; convert to salt (insoluble)

Alternately • Eg ergotamine from ergot

• Drug extracted with polar solvents

Step 2 • Water, EtOH, MeOH, Aq. Alc mixture or acidified aq. Sol
ISOLATION PROCESS

• Converted to thick syrup by evaporation

Step 3
• Partitioning between aqueous and organic solvent
Step 4 • Aqueous phase made alkaline with Na carbonate or ammonia

• Basic aq. Sol extracted with organic solvent; dried using Na

Step 5 sulphate
ALTERNATE ISOLATION METHOD

• Treatment of drug with ammonia (free base formed)

Step 1

• Extracted with organic solvent

Step 2

• **not useful to extract alkaloids with quaternary nitogen

PURIFICATION

• Direct crystallization from solvent

• Steam distillation- volatile alkaloids (Coniine, sparteine, nicotine)

• Chromatographic techniques- thin layer, column, GC, HPLC, HPTLC, ion exchange

• Gradient pH technique
CHEMICAL TESTS FOR IDENTIFICATION

Wagner's test: (I2/KI):Reddish brown precipitate

Mayer’s: (HgCl2) Creamy precipitate with True alkaloid

Hager's test: (Picric acid) Yellow precipitate with True alkaloid

Dragendorff’s: (Potassium Bismuth Iodide) Reddish Brown precipitate

Tannic acid solution: precipitation as alkaloidal tannate

 Mayer’s test

Wagner’s test

https://media.neliti.com/media/publications/286181-preliminary-phytochemical-screening-qual-f501b8b2.pdf
CLASSIFICATION OF ALKALOIDS

1. Pharmacological
2. Taxonomic
3. Biosynthetic
4. Chemical
CHEMICAL CLASSIFICATION
CHEMICAL CLASSIFICATION
CHEMICAL CLASSIFICATION
CHEMICAL CLASSIFICATION
PROTO ALKALOIDS (NON-HETEROCYCLIC N)
 Ornithine

TROPANE ALKALOIDS
Tropane nucleus
Tropane alkaloids are ornithine derived
Fusion of pyrrolidine & piperidine ring with common methylated nitrogen.
Methylated nitrogen nucleus containing drugs are chemotaxonomic
characters of family Solanaceae.
Common ones are: Hyoscyamine (l), Hyoscine (l), Atropine
BELLADONA
BELLADONA

• Synonyms: Deadly night shade leaves, Poison black cherry

• Biological Source: Consists of dried leaves or the leaves and other

aerial parts of Atropa belladonna Linn.(European belladonna) or Atropa
acuminata (Indian belladonna) or mixture of both the species collected
when the plant is in flowering state. Family: Solanaceae
• Contains not less than 0.3% of alkaloid calculated as l-hyoscyamine

• Geographical source: Europe, India (Shimla to Kashmir, HP, Jammu)

 CHEMICAL CONSTITUENTS

• Main alkaloids are l-hyoscyamine and its racemic form is atropine

• Belladonine, scopoletin (l-methyl aesculetin), hyoscine, pyridine, N-methyl
pyrroline
• Homotropine is synthetic tropane alkaloid

Hyoscyamine (l)
CHEMICAL CONSTITUENTS

Atropine
Hyoscyamine
Hyoscine
Racemic forms
SPECIFIC CHEMICAL TEST:
VITALI MORINS

• Tropane Alkaloid + fuming Nitric acid 🡪 evaporate to dryness🡪 Nitrated residue

obtained 🡪 dissolve in acetone and to this add methanolic KOH 🡪 VIOLET
COLORATION
• Hyoscine hydrobromide + AgNO3 🡪 Yellowish white ppt, soluble in ammonia.
THERAPEUTIC USES

• Atropine is parasympatholytic drug with Anticholinergic properties

• Used to reduce secretions like sweat, saliva, gastric juices
• It also decreases smooth muscles motility (anti spasmodic property)
prevents gripping
• It possess Mydriatic property, dilates pupil and is used for retina
examination (ATROPINE)
• Hyoscyamine is given in peptic ulcers.
MARKETED FORMULATION
INDOLE ALKALOIDS

• True alkaloids Derived from amino acids

• Contain nitrogen in heterocyclic ring

• Derived from tryptophan alkaloid

Tryptophan
RAUWOLFIA
RAUWOLFIA

• Synonyms: Serpentina Roots, Sarpagandha, Chhotachand, Sarpagandha

• Biological Source: Dried roots of Rauwolfia serpentina; Family:

Apocynaceae. (It contains NLT 0.15% of reserpine and ajmalcine).

• Geographical Source: Asia, Africa, Sri Lanka; India (UP, Bihar, Orissa, TN)
CHEMICAL CONSTITUENTS

• About 30 indole alkaloids; range from 0.7-3%

• Reserpine is the main alkaloid
• Other indole alkaloids are: Rescinnamine, deserpedine, Ajmalicine,
ajmaline, reserpinine, yohimbine, serpentine, serpentinine
• Reserpine: ester of trimethoxy benzoic acid
• Rescinnamine: ester of trimethoxycinnamic acid
• Other constituents are: Oleo-resin, phytosterol, fatty acid, alcohol,
sugar.
CHEMICAL CONSTITUENTS

Reserpine Deserpidine
CHEMICAL CONSTITUENTS

Rescinnamine
CHEMICAL TEST:

•Van Urk Test: Indole alkaloid + H2SO4 + p-dimethyl amino benzaldehyde (Ehrlich
reagent) violet-red color
•(Indole alkaloids)
THERAPEUTIC USES

• Used in mild hypertension

• MOA: It lowers BP by depleting store of catecholamine at nerve
ending, prevent re-uptake of nor-epinephrine at storage sites, allowing
enzymatic destruction of neuronal transmitter.
• Neuropsychiatric disorder (anti-anxiety)
• Ajmalicine: treatment of circulatory diseases, in relief of obstruction of
normal cerebral blood flow
• Deserpidine: tranquilliser, antihypertensive
GUESS WHAT?
VINCA

• Synonyms: Catharanthus, Periwinkle

• Biological Source: It is the dried whole plant of Catharanthus roseus

also called Vinca rosea; Family: Apocyanaceae

• Geographical Source: Indigenous to Madagascar, cultivated in India,

USA, South Africa, Europe, Australia
CHEMICAL CONSTITUENTS

• Indole Alkaloids
• 20 dimeric indole-dihydroindole alkaloids possess oncolytic activity
• Vincristine and Vinblastine most significant also known as
Catharanthine
• Dihydroindole alkaloid: Vindoline
CHEMICAL CONSTITUENTS
 THERAPEUTIC USES

• Vincristine sulphate: antineoplastic: arrest mitosis at the metaphase,

used in acute leukemia for children, Hodgkin’s disease, reticulum cell
sarcoma, lympho sarcoma, myosarcoma

• Hypotensive & Anti diabetic

GUESS WHICH PLANT??
OPIUM
(ISOQUINOLINE/PHENENTHRINE ALKALOID)

• Synonym: Raw opium

• Biological Source: Dried latex obtained by incision from the unripe
capsules of Papaver somniferum Linn.
• Dried or partly dried by heat or spontaneous evaporation, and worked
into somewhat irregularly shaped masses (natural opium) or moulded into
masses of more uniform size and shape (manipulated opium) Family:
Papaveraceae
• It contains not less than 9.5% of morphine calculated as anhydrous
morphine
OPIUM

• Geographical source: India, Pakistan, Afghanistan, Turkey, Russia, China

and Iran
• India- MP, UP, Punjab, Rajasthan; Govt opium factory is at Ghazipur
• Being a potent narcotic the cultivation and other aspects of opium are
governed by the respective governments in the different countries.
• In India all the activities about opium are governed by the Narcotic Drugs
and Psychotropic Substances Act, 1985
• https://youtu.be/tlr_w3rXX5o
• Opium farming.mp4
Cultivation:
Grown from November to March.
Propagation is done by seeds. Seeds are mixed with sand and are sown.
Soil: highly fertile, well drained loamy soil with fine sand, should contain organic matter,
N containing, pH around 7.
Nitrogen and phosphorus have good effects on growth of plant.
Capsules are incised vertically in the afternoon with the help of specific knife called
‘nushtur’.
Penetration should be optimum (2 mm). If incision is too deep then latex will flow
inside while superficial incision gives less latex. Latex exudes out and thickens in night.
Scrapped and collected next morning by an iron spatula called ‘Charpala’.
Process is repeated for about 4 times on the same capsule with 2 days interval
Latex is collected and dried further.
Capsules are collected and further the seeds are used as spice.
CHEMICAL CONSTITUTION

• Latex contains alkaloids derived from phenylalanine and tyrosine

• Benzylisoquinoline: narcotine (noscapine), narceine, papaverine
• Phenanthrene: morphine, codeine, thebaine
 CHEMICAL CONSTITUENTS

Heroin
Papaverine Narcotine

Opium alkaloids are present as salts of meconic acid

Chemical Test:

1. Test for meconic acid: Opium is dissolved in water, filtered, to

the filtrate add FeCl3 🡪 deep reddish-purple color, which
persists even after addition of HCl

2. Test for Morphine: Morphine solution + potassium

ferricyanide + FeCl3 🡪 bluish green color
Uses:
Opium: Sedative-Hypnotic Class, Action is due to Morphine
Morphine: potent analgesic given in severe pain (operative
conditions), due to central narcotic effects, causes addiction.
Sedates cerebrum and medulla, respiration, emetic & cough
reflex center
Triggers Chemo receptor trigger zone, nausea, vomiting
Codeine: relieves local irritation in bronchial tract, antitussive
Papaverine: smooth muscle relaxant of bronchial, intestinal and
blood vessels (vasodilator)
Narcotine: cough reflex depressant
Heroin: diacetyl morphine: more narcotic, analgesic property
than morphine
Apomorphine: emetic & in drug poisoning
Hydro morphine: narcotic analgesic, habit-forming tendency is
less.
THANK YOU