Alkaloids

Definition:
The term “alkaloid” (alkali-like) is commonly used to
designate basic heterocyclic nitrogenous compounds of
plant origin that are physiologically active.

Alkali like
Basic in nature
Nitrogen in heterocyclic ring
Physiologically active
Heterocyclic compounds are organic compounds
with a ring structure that contains in the cycle at least
one carbon atom and at least one other element, such
as N, O, or S. The most common cycles contain five
or six atoms, with the stability of these rings being
higher than that of three, four, seven, or larger rings.
Deviation from Definition:
• Basicity: Some alkaloids are not basic e.g.
Colchicine, Piperine, Quaternary alkaloids.
• Nitrogen: The nitrogen in some alkaloids is
not in a heterocyclic ring e.g. Ephedrine,
Colchicine, Mescaline.
• Plant Origine: Some alkaloids are derived
from Bacteria, Fungi, Insects, Frogs,
Animals.
Classification:
• True (Typical) alkaloids that are derived
from amino acids and have nitrogen in a
heterocyclic ring. e.g Atropine
• Protoalkaloids that are derived from
amino acids and do not have nitrogen in a
heterocyclic ring. e.g Ephedrine
• Pseudo alkaloids that are not derived
from amino acids but have nitrogen in a
heterocyclic ring. e.g Caffeine
• False alkaloids are non alkaloids give
false positive reaction with alkaloidal
reagents.
 Distribution and occurrence:
• Rare in lower plants.
• Dicots are more rich in alkaloids than
Monocots.
• Families rich in Alkaloids: Apocynaceae,
Rubiaceae, Solanaceae and
Papaveracea.
• Families free from Alkaloids: Rosaceae,
Labiatae
 :Distribution in Plant
• All Parts e.g. Datura.
• Barks e.g. Cinchona
• Seeds e.g. Nux vomica
• Roots e.g. Aconite
• Fruits e.g. Black pepper
• Leaves e.g. Tobacco
• Latex e.g. Opium
:Forms of Alkaloids
• Free bases
• Salts with Organic acids e.g. Oxalic,
acetic acids
• Salts with inorganic acids e.g. HCl, H2SO4.
• Salts with special acids:
e.g. Meconic acid in Opium
Quinic acid in Cinchona
• Glycosidal form e.g. Solanine in Solanum.
Function in Plants
• They may act as protective against insects
and herbivores due to their bitterness and
toxicity.
• They are, in certain cases, the final products
of detoxification (waste products).
• Source of nitrogen in case of nitrogen
deficiency.
• They, sometimes, act as growth regulators in
certain metabolic systems.
• They may be utilized as a source of energy in
case of deficiency in carbon dioxide
assimilation.
:Nomenclature
Trivial names should end by "ine". These names may
refer to:
– The genus of the plant, such as Atropine from Atropa
belladona.
– The plant species, such as Cocaine from Erythroxylon
coca.
– The common name of the drug, such as Ergotamine
from ergot.
– The name of the discoverer, such as Pelletierine that
was discovered by Pelletier.
– The physiological action, such as Emetine that acts as
emetic, Morphine acts as narcotic.
– A prominent physical character, such as Hygrine that is
hygroscopic.
 :Prefixes and suffixes
Prefixes:
• "Nor-" designates N-demethylation or N-demethoxylation,
e.g. norpseudoephedrine and nornicotine.
• "Apo-" designates dehydration e.g. apomorphine.
• "Iso-, pseudo-, neo-, and epi-" indicate different types of
isomers.
Suffixes:
• "-dine" designates isomerism as quinidine and
cinchonidine.
• "-ine" indicates, in case of ergot alkaloids, a lower
pharmacological activity e.g. ergotaminine is less potent
than ergotamine.
 :Physical Properties
I- Condition:
• Most alkaloids are crystalline solids.
• Few alkaloids are amorphous solids e.g. emetine.

• Some are liquids that are either:

Volatile e.g. nicotine and coniine, or
Non-volatile e.g. pilocarpine and
hyoscine.
II- Color:
The majority of alkaloids are colorless but some are
colored e.g.:
• Colchicine and berberine are yellow.
• Canadine is orange.
 :Physical Properties
III- Solubility:
• Both alkaloidal bases and their salts are soluble in alcohol.
• Generally, the bases are soluble in organic solvents and
insoluble in water
Exceptions:
• Bases soluble in water: caffeine, ephedrine, codeine,
colchicine, pilocarpine and quaternary ammonium bases.
• Bases insoluble or sparingly soluble in certain organic
solvents: morphine 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: quinine monosulphate.
• Salts soluble in organic solvents: lobeline and apoatropine
hydrochlorides are soluble in chloroform.
 :IV- Isomerization
• Optically active isomers may show different
physiological activities.
• l-ephedrine is 3.5 times more active than d-ephedrine.
• l-ergotamine is 3-4 times more active than d-ergotamine.
• d- Tubocurarine is more active than the corresponding l-
form.
• Quinine (l-form) is antimalarial and its d- isomer
quinidine is antiarrythmic.
• The racemic (optically inactive) dl-atropine is
physiologically active.
 :Chemical Properties
I- Nitrogen:
• Primary amines R-NH2 e.g. Norephedrine
• Secondary amines R2-NH e.g. Ephedrine
• Tertiary amines R3-N e.g. Atropine
• Quaternary ammonium salts R4-N e.g d-Tubocurarine

II- Basicity:
• R2-NH > R-NH2 > R3-N
• Saturated hexacyclic amines is more basic than aromatic
amines.
:III- Oxygen

• Most alkaloids contain Oxygen and are

solid in nature e.g. Atropine.

• Some alkaloids are free from Oxygen and

are mostly liquids e.g. Nicotine, Coniine.
 :IV- Stability
• Effect of heat:
Alkaloids are decomposed by heat, except
Strychnine and caffeine (sublimable).
• Reaction with acids:
1- Salt formation.
2- Dilute acids hydrolyze Ester Alkaloids e.g.
Atropine
:Conc. acids may cause
• Dehydration:
.
Atropine → Apoatropine
Morphine → Apomorphine
• Effect of light and Oxygen:
Some alkaloids are unstable when exposed to
light and Oxygen:

Oxygen
Eserine Rubreserine
Alkaline solutions

Reserpine Decomposition

Ergot Alkaloids Lumi Alkaloids

(Inactive)
:Qualitative test for Alkaloids

• Precipitation Reagents:
They are used to:
1- Indicate the absence or presence of Alkaloids
2- Test for complete of extraction

Disadvantages: Some non alkaloids interfere

such as Proteins, lactones, coumarins
-Detection of alkaloid:-
-Wagner's test: (I2/kI): Reddish brown precipitate.

.Mayer’s: (HgCl2 Creamy precipitate with True alkaloid-

Hagger's test: (Picric acid) Yellow precipitate with True-

.alkaloid

Dragendroff: (Potassium Bismuth Iodide) Reddish-

.Brown precipitate

Tannic acid solution: different alkaloid colored-

.precipitate
 ?How to verify Functional Groups
IR:
carbonyl, amide, ester, substituted phenyl,
hydroxy, amine, alkyl, ether, etc

:Optical property

Specific optical rotation: similar skeleton

and conformation
 Classification of Alkaloids

Me
N

N N N
H H N

Piperidine Pyridine Pyrrolidine Tropane Quinoline

NH N NH
N NH N
H N N N
Isoquinoline Tetrahydro- Indole Imidazole Purine
isoquinoline
 Tropane Alkaloids -1
Tropane alkaloids are a class of bicyclic alkaloids and
secondary metabolites that contain a tropane ring in their
chemical structure. Tropane alkaloids occur naturally in
many members of the plant family Solanaceae

:Occurrence •
Hyoscyamus niger
Atropa belladonna
Datura stramonium
Main Alkaloids are: (Scopolamine)
.Atropine, Hyoscyamine, Hyoscine -1
Hyoscyamine is the major natural alkaloid with
.negative optical rotation (l- form)
During extraction hyoscyamine racemizes to
.the optically inactive dl Atropine
Both alkaloids composed of tropine base and
.tropic acid

Hyoscyamine
 Hyoscine (Scopolamine)
Hyoscine is an ester of l-tropic acid with scopoline •
.base
.Hyoscine is a syrupy liquid •

Hyoscine
 Hyoscyamus niger

Family: Solanaceae

Common Name: Henbane and stinking

nightshade) is a poisonous plant in the
nightshade.

Part Used: Leaves, seeds and juice

Habitat: Europe, Siberia, UK, and Ireland

Traditional Uses: Herbal medicine for ailments of the bones, rheumatism,

toothache, asthma, cough, nervous diseases, and stomach pain. It might
also be used as analgesic, sedative, and narcotic in some cultures.
Adhesive bandages with henbane extract behind the ear are reported to
prevent discomfort in travel-sick people
The side effects of henbane ingestion are dryness in the mouth, confusion, visual
illusions, bizarre thoughts, locomotor and memory disturbances
B. Name : Atropa belladona
F: Solanaceae
Common Name: Deadly nightshade
is a toxic perennial herbaceous plant

Habitat: Europe, Asia & Turkiye

The common name belladonna originates from its historic use by women, as bella-
donna is Italian for "beautiful woman". Drops prepared from the belladonna plant
were used to dilate women's pupils, an effect considered to be attractive. Belladonna
drops act as a muscarinic antagonist, blocking receptors in the muscles of the eye
that constrict pupil size. Belladonna is currently rarely used cosmetically, as it carries
the adverse effects of causing minor visual distortions, inability to focus on near
objects, and increased heart rate. Prolonged usage was reputed to cause blindness.
Part Used: Whole plant
Active Constituents: atropine, scopolamine, and hyoscyamine
All parts of the plant contain tropane alkaloids; roots have
up to 1.3%, leaves 1.2%, stalks 0.65%, flowers 0.6%, ripe
berries 0.7%, and seeds 0.4% tropane alkaloids
Leaves reach maximal alkaloid content when the plant is
budding and flowering, roots are most poisonous in the end
of the plant's vegetation period. Belladonna nectar is
transformed by bees into honey that also contains tropane
alkaloids. The berries pose the greatest danger to children
because they look attractive and have a somewhat sweet
taste.
 Datura stramonium

Common names ultimately from Sanskrit dhattūra,

thorn apple, jimsonweed
Poisonous flowering plant
Family: Solanaceae
Habitat: Asia, Europe
Constituents: tropane alkaloids atropine, hyoscyamine,
scopolamine

Traditional Uses:

During 9th-century
Treatment for asthma,
External inflammations and haemorrhoids
 Alkaloids in the form of HCl salts

1- Alkalinize by NaHCO3 pH 7.5

2- Extract with Ether

Ether Aqueous layer

Hyoscine free base Atropine & Hyoscyamine HCl
(pKa = 6.2) (pKa = 9.3)

Convert to oxalate salts,

Fractional Crystallization
(Acetone/ Ether)

Atropine Oxalate Hyoscyamine Oxalate

Crystals Solution
:Gerrard’s test
Alkaloid + 2% HgCl2 in 50% Ethanol → Red colour Atropine
Red after warming Hyoscyamine
White ppt Hyoscine
:Pharmacological actions and uses 
:The three Alkaloids are anticholinergic agents
.Decrease saliva and GIT secretions so used preoperative-
Decrease motility of smooth muscles so used as-
.antispasmodics
-Stimulate respiratory system.
-A mydriatic (causes dilatation of the eye pupil).
-An antidote to organophosphorus insecticides.
-Hyoscine has more central effect so it is sedative and
hypnotic.
-Hyoscine is mainly used as antiemetic.
:Quinoline alkaloid
Botanical source: Cinchona succirubra
Family: Rubeaceae

: Cinchona Alkaloid
:main compound 4

Quinine, Cinchonine, Cinchonidine, Quinidine

Part Used: Dried barks

- .

:Pharmacological effect
Antimalaria, Antiarhythmitic
Detection under U.V 366nm
.blue fluorescent with sulfuric acid
 Quinidine

Cinchonidine

Cinchonine
 B. Source: Nicotiana tobacum
F: Solanaceae
Part used: Leaves
Constituents: Nicotine, Yohimbine,
:Nicotinic acid derivatives
Nicotine is a very toxic. compound

-Pharmacological effect:
-It works on nicotinic receptor
(start by stimulation then
inhibition.
-Highly hydrophobic, so can cross
blood brain barrier.
The plant is native to the Caribbean, where the Taíno
people were the first recorded peoples to use it and
cultivate it. In 1560, Jean Nicot de Villemain, then
French ambassador to Portugal, brought tobacco
seeds and leaves as a "wonder drug" to the French
court. It was considered a decorative plant at first,
Uses as: CNS stimulant, dental carries,
Alzheimer
.It's liquid compound, yellowish
.Oxidized by light and will form brown color
Toxicity: Cancer which give nitrous amine (very
nuclephilic) lead to change in DNA structure,
Pulmonary and cardiac disease, Effect in
hepatic system lead to increase metabolite
Nicotine
 : Piperdine Alkaloid
.)Lobelia(
:Biosynthetic origin
.Botanical sours form Lobelia inflata Lobeliaece
:Pharmacological effect
.CNS Stimulant (cholinergic agonist)
Uses: For premature babies (has Problem
in respiration) so give cortisone to dilution
.lung
High dose cause tonic spasm for skeletal
.and smooth muscle
Lobeline
 : Arecoline Alkaloid
Botanical sours are seed of Areca catechu
.Arecaceae
Pharmacological action: Parasympathomimetic
work on messianic receptor and in high dose work
on nicotinic receptor
Uses:, Alzheimer disease, has Psychocyco active
.”effect “Cigarette as cocaine in malaise

It causes redness of mouth, teeth an saliva, when

.use for long time cause buccal cancer
Arecoline
 Imidazole Alkaloid
:Biosynthetic origin
Examples: Pilocarpine
.Botanical sours are Pilocarpus jaborandi Rutaceae
Pharmacological effect: Parasympathomimetic
Uses: in Glaucoma (wide and narrow angle
.Glaucoma) and myosis of the eye
.Keep away from light
Side effect: bronco contraction, brady
cardiac, not first choice for glaucoma
because headache and increase in
.lacrimation
Imidazole alkaloid
 Indole alkaloids

Ergot
Periwincle
Rauwolfia
Nux-vomica
Physostigma
Ergot refers to a group of fungi
This fungus grows on rye and related
plants, and produces alkaloids that can
cause ergotism in humans and other
mammals who consume grains.
Biological source: Claviceps
purpurea
F: Clavicipitaceae
P. used: grains or seeds contaminated
with the this fungus
Ergot alkaloids are classified as:
Derivatives of 6,8-dimethylergoline and lysergic acid derivatives.

:Ergotamine and Ergometrine

.dopamine and Serotonin &
Lysergic acid derivatives (LSD) &
:Uses of Ergotamine
Migraine (at low dose has agonist
.adrenergic)
lysergic acid
.Make vasoconstriction
.Oxytocic (stimulate or induce labor)
.Postpartum hemorrhage (vasoconstriction)
Sometimes leading to gangrene and loss of limbs due to severely restricted blood
.circulation
Ergotamine

Ergometrine
Nux-vomica
B. Name: Strychnus nux-vomica
Part used: Seeds
.F: Loganiaceae
Very toxic compounds Strychnine and Brucine which block
. Neurotransmission from the spinal cord to the brain
Used only for study the sympathetic and
.parasympathetic action of drug
Detection : Nitric acid: Strychnine will give
.yellow PPT. Brucine will give red PPT
R= H: Strychnine
R= OCH3: Brucine
Nux vomica is used for diseases of the digestive tract,
disorders of the heart and circulatory system, diseases of
the eye and lungs. It is also used to
treat depression, migraine, headache and anemia. It is also
as an appetite stimulant.
In manufacturing, nux vomica is used as rat poison. That’s
because it contains strychnine and brucine, two deadly
chemicals, that affect the brain and cause
muscle contractions. This can lead to convulsions and death
 Physostigmine and Neostigmine Alkaloid
B. Name: Physostigma venenosum
F: Fabaceae
Part used: Seeds
.Common name (Calaber been)
Pharmacological effect: Irreversible choline esterase
.inhibitor (parasympathomimmtic)
Used glaucoma and increase excretion of aqueous
.hummer and will decrease IOP
Precautions: Give I.V or I.M for it toxicity
.Neostgmine: Not an indol alkaloid
action normalize contraction of striated muscle by
.facilities nerve impulse
.Soluble in water so can use be given S.C
:Used
.For diagnosis of myasthenia gravis
.Post operation Bladder surgery
Side effect: Miosis, Convolution, Respiratory arrest,
.Brady cardiac
B. Name: Catharanthus roseus (Vinca rosa)
F: Apocynaceae
P. used: Arial part
Active Constituents: Vincristine and vinblastine
.It's cytotoxic used for Hodgkin's and non Hodgkin's disease

:Pharmacological effect
.Used: Anticancer single or combination therapy
Side effect: Alopecia, Gastrointestinal (Nausea, vomiting,
.ulcer)
:Rauwlfia Alkaloid
B. N: Rauwolfia serpentina
F: Apocyneceae
Local name: Indian snakeroot
Part used: Roots
Habitat: Asia
Examples: Reserpine and Rescinnamine
:Mode of action
Anti hypertensive, depletion of catecholamine
peripherally (decrease ephedrine and nor
ephedrine), depletion of central neurotransmitter
:(mainly serotonin) Pharmacological effect
Insanity: Popularly known as pagal-ki-dawa
Insomnia: This herb has sedative properties
High Blood Pressure
Hysteria: Rauwolfia is found beneficial in relieving
hysteria
Ressenamine
Morphinane type alkaloids:
Opium alkloaid:
Botanical source:
dried latex of Pappaver somniferum papaveraceae
Pharmacological action:
Medecinal uses :
Morphine:
Codeine:
Thebaine:
Papaverine:
Heroin:
Noscapine:
Codeine Heroine Morphine

Pappaverine :Thebaine Noscapine

methoxy codeine-6 )Narcotine(
Ipecacuahna alkaloids:
B.N: Cephalis ipecacuanha
F: Rubiaceae
P. Used : Rhizome
Constituents:
Emetine alkaloid:
Cephaline alkaloid
Habitat: Panama, Colombia, and Brazil
Uses: he roots were used emetic

R= CH3: Emetine
R= H: Cepheline
B. N: Aconitum napellus
Highly toxic flowering plants
F: Ranunculaceae
P. used: Aconite root
Constituents: Aconitine,
Several poisonous compounds, including
enough cardiac poison that it was used on spears
and arrows for hunting and battle in ancient times
Uses: In gardens for its attractive spike-like
In homeopathy, aconite is used to treat fear, anxiety,
and restlessness; acute sudden fever; symptoms from
exposure to dry, cold weather or very hot weather;
tingling, coldness, and numbness; influenza or colds
with congestion; and heavy, pulsating headaches
Precautions: When taken by mouth: Aconite is unsafe.
All species of the plant and products containing it are
dangerous. Aconite contains a strong, fast-acting poison
that causes severe side effects such as nausea, vomiting,
breathing problems, heart problems, and death
:Proto alkaloids

B.N: Ephedra sinica

F: Ephedraceae
Constituents: Ephedrine & pseudoephedrine
,Uses: To treat asthma, bronchitis
.and hay fever
Ephedra is also prescribed for
symptoms of cold and flu, including
nasal congestion, cough, fever & chills

:Adverse effects
Stroke, heart attack, and sudden
death

Ephedrine
 B.N: Colchicum autumnale
F: Liliaceae
,P. Used: The seed, bulb, leaves
and flower are used to make medicine
Constituents: Colchicine
:Pharmacological action
:Uses
Gout
Inflammatory disorders

Colchicine
 Purine (Xanthine) Alkaloids
• The purines are consisting of a six-membered pyrimidine ring fused to a
five-membered imidazole ring.

• The pharmaceutically important bases of this group are all methylated

derivatives of 2,6 dioxy-purine (Xanthine). This group includes mainly
Caffeine, theobromine and theophylline alkaloids.

• These alkaloids are weak bases, they give no precipitate with Mayer's
reagent.

6 H O
7 H
1 N 5 N N
HN
8
2
N 4 N O N
9 N
3 H
Purine Xanthine
Pseudo alkaloids

Caffeine Theobromine

Thyophyline
 Caffeine, Theobromine and Theophylline
O R3
R1 N
N R1=R2=R3=CH3 Caffeine
R1=H, R2=R3=CH3 Theobromine
R1=R2=CH3, R3=H Theophylline
O N N

R2

Caffeine
• Occurrence:
Tea leaves (2- 5%), Coffee seeds (1-2 %), Cola leaves (2- 3%),
Gurana seeds (2.5- 5 %) and Cacao seeds, (0.2- 0.5 %).
• Properties:
Water soluble.
• Uses:
Caffeine has a CNS stimulant effect, it is used mainly to relieve headache.
 Theobromine
• Occurrence: Cacao seeds.
• Properties:
1- Sparingly soluble in water. 2- Amphoteric.
• Uses: Theobromine is used mainly as a diuretic.

Theophylline
• Occurrence: Traces in Tea leaves, mostly synthetic.
• Properties: 1- Sparingly soluble in water.
• Uses:
Theophylline and derivatives are smooth muscle relaxant especially in the
upper respiratory tract. They used as bronchodilator. Theophylline also
act as duiretic.
• Color tests:

 Murexide test: (caffeine, theobromine and theophylline).

Crystals of caffeine + drops of concentrated HCl and traces of KClO3
→evaporated on water bath → red color is produced wich turns to
violet on exposure to ammonia vapor.

 Tannic acid test: (caffeine and theophylline):

A concentrated solution of the alkaloid + tannic acid → white
precipitate is obtained.

 Ferrous sulfate test: (theobromine):

To a solution of the alkaloid + drops of concentrated HCl + few drops of
Br2­water + a drop of FeSO4 + few drops of ammonia → Blue color.
 Steroidal Alkaloids

• These contain the perhydrocyclopentano-phenanthrene skeleton

characteristic of sterols.

They usually occur in glycosidal combination with sugars and thus •

.called gluco-alkaloids e.g. Veratrum alkaloids

H
H H

HO
Steroidal alkaloids are nitrogenous derivatives of
natural steroids. They are an important class of
alkaloids and conventional secondary metabolites that
occur in plants including Solanaceae, Liliaceae,
Apocynaceae, amphibians and marine organisms.
 Veratrum alkaloids -1
• They are of two types:
1- Typical or atypical steroidal alkamines containing one or two
non estrified hydroxyl groups e.g. Rubijervine and Veratramine.
2- Highly oxygenated alkamines estrified with organic acids e.g.
Protoveratrines A& B.
• Uses:
The second group posses hypotensive effect.

OH
N
N

HO

HO HO

Rubijervine Veratramine
 Veratrum alkaloids

The veratrum alkaloids, which are chemically similar to

steroids, include protoveratrine, veratridine, and jervine.
These agents were introduced in the 1950s as
antihypertensive agents; however, they were found to
have a narrow therapeutic index and their use was
discontinued.

Used as emetics and as drugs for neuralgia. Veratrum extracts

and purified alkaloids was proposed for treating arterial
hypertension.