ALKALOIDS

PHARM MAXMILIAN J NZOWA

PST 5 SEMISTER 2
Session 18: Introduction to Alkaloids

• Learning Tasks
• By the end of this session students are expected to be able to:
• Explain the occurrence and distribution of alkaloids
• Explain naming of alkaloids
• Explain properties of alkaloids
Occurrence and Distribution of Alkaloids

• Alkaloids are basic naturally occurring compounds containing one or

more nitrogen atoms usually in a heterocyclic ring and have a marked
physiological action on man or other animals
• Some alkaloids occur in certain families while others only occur in
specific species
• Alkaloids are highly found in apocynaceae, rubiaceae, solanaceae and
papaveracea
• Alkaloids are not found in rosaceae and labiatae families
• Alkaloids are produced by a large variety of organisms, including
bacteria, fungi, plants, and animals
 Meaning and Definition
• Meaning
–The term “alkaloid” means …….???
• Definition
–Difficult because they very much resemble the
naturally occurring complex amines
–But can simply be defied as
“Basic naturally (typically from plants) occurring
compounds containing one or more nitrogen
atoms usually in a heterocyclic ring and have a
marked physiological action on man or other
animals”
 The Nitrogen of Alkaloids
• The N atom can either be 1° (mescaline), 2°
(ephedrine), 3° (atropine) or 4°
(tubocurarine)
• This N feature affects the alkaloid derivatives
which can be prepared and the isolation
procedures.
 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 Origin:
• Some alkaloids are derived from Bacteria, Fungi, Insects, Frogs, Animals.
 Characteristics
•Bitter tasting, usually white solids
•Except nicotine which is brown liquid
•Precipitated with heavy metal iodides
•Except caffeine
•They are basic
•Combine with acids to form water soluble
salts
 Alkaloids: Occurrence & Distribution
• In bacteria (P. aeruginosa), rarely
in fungi e.g. pscilocin from
hallucinogenic mushrooms)
• Some occur in several genera from
different species (caffeine), but
most in closely related species.
• Some occur in certain families
(hyoscyamine), while others only
in specific species (morphine).
• Plants rarely contain more than 1
type of alkaloid.
• All alkaloids of one plant have a
common biogenetic origin
 Alkaloids: Occurrence & Distribution
• Alkaloids occur in all plant
parts, but are usually
localized in one organ (e.g.
the bark or seeds).
• Vary widely from part to
part – some plant parts
may contain no alkaloids.
• Occasionally, different
alkaloids also form in
different parts of the plant
Alkaloids: Occurrence & Distribution
• Generally in Plants;
• Alkaloids are 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
• Occur in free state, as salts, or as amine or
alkaloid N-oxides
Alkaloids: Occurrence & Distribution
• Alkaloids may occur;
• In Free state (e.g. as free bases)
• As Salts
• with Organic acids e.g. Oxalic, Acetic acids
• with inorganic acids e.g. HCl, H2SO4.
• with special acids: e.g. Meconic acid in
Opium, Quinic acid in Cinchona
• As Glycosides e.g. Solanine in Solanum sp
• As Alkaloid N-oxides (N-oxidation products of
alkaloids) e.g. reserpine, strychnine etc.
 Distribution of Alkaloids 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
 Functions in the Plant
• Protect against insects and herbivores due to their bitterness and toxicity.
• Are final products of detoxification (waste products) in some cases.
• Source of nitrogen in case of nitrogen deficiency.
• Act as growth regulators in certain metabolic systems.
• Are source of energy in case of deficiency in carbon dioxide assimilation.
remember

• Functions of alkaloids in the plant;

• Protect against insects and herbivores due to their bitterness and toxicity
• Are final products of detoxification in some cases.
• Source of nitrogen in case of nitrogen deficiency
• Act as growth regulators in certain metabolic systems.
Properties of Alkaloids

• Physical properties
• Most alkaloids are crystalline solids, a few are amorphous solids e.g. emetine.

• Some are liquids that are either volatile or non-volatile

• Majority of the alkaloids are colorless but some are colored;
• Alkaloidal bases are soluble in organic solvents and insoluble in water
• Salts of alkaloids are usually soluble in water and, insoluble or
sparingly soluble in organic solvents
• Alkaloids are bitter tasting
• Many alkaloids are extremely toxic to other organisms.
• Alkaloids exhibit isomerism e.g. optical isomerism i.e L-ephedrine is 3.5 times
more active than d-ephedrine
• Chemical properties
• Alkaloids are amines (may be primary, secondary, tertiary and quaternary)
• Most alkaloids contain oxygen and are solid in nature e.g. Atropine.
• Alkaloids are decomposed by heat, except Strychnine and Caffeine
• Alkaloids react with acids to form salts
• Dilute alkalis liberate most alkaloids from their salts e.g. NH3
• Some alkaloids are unstable when exposed to light and oxygen while others
are not
Nomenclature

Morpheus
Nomenclature
•Numerous methods can be used to name
alkaloids
•Names should end by "ine". These names
may be derived from:
•Generic plant name – Atropine from
Atropa belladonna
•Specific name of the plant – Cocaine from
Erythroxylum coca.
•Names of loved ones e.g. Cathelenine
Nomenclature
• Common name of the plant – Ergotamine from
ergot (rye)
• Physiological action of the plant – Emetine
producing emesis
• A prominent physical character e.g. Hygrine
which means hygroscopic
• The name of the discoverer e.g. Pelletierine,
discovered by Pelletier.
• Others – e.g. morphine derived from ancient
Greek mythology – Morpheus – god of dreams
 Prefixes
Prefixes:
& Suffixes
• "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.
Naming of Alkaloids

• Alkaloids are named by various methods

• Names of alkaloids end by "ine". These names may be derived from:
• Generic plant name – Atropine from Atropa belladonna
• Specific name of the plant – Cocaine from Erythroxylum coca
• Names of loved ones e.g. Cathelenine
• Common name of the plant – Ergotamine from ergot (rye)
• Physiological action of the plant – Emetine producing emesis
• Prefixes and Suffixes used in naming of alkaloids
• 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 which is less potent than ergotamine
• 
Prefixes & Suffixes
Suffixes:
•"-dine" designates isomerism as Quinidine
and Cinchonidine.
•"-ine" indicates, in case of ergot alkaloids,
a lower pharmacological activity e.g.
Ergotaminine which is less potent than
ergotamine.
 Properties of Alkaloids
Physical Properties
•Physical State
•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
Properties of Alkaloids
Physical Properties
•Color
•Majority are colorless but some are
colored;
•Colchicine and berberine are yellow.
•Canadine is orange.
•The salts of sanguinarine are copper-red
 Properties of Alkaloids
Physical Properties
•Solubility
•Both alkaloidal bases and their salts are
soluble in alcohol
•Generally, the bases are soluble in
organic solvents and insoluble in
water
Properties of Alkaloids
Physical Properties
•Solubility (cont’d..)
• 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.
 Properties of Alkaloids
Physical Properties
• Solubility (cont’d..)
• 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.
 Properties of Alkaloids
Physical Properties
•Isomerism
•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.
Properties of Alkaloids
Physical Properties
•Isomerism (cont’d…)
•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.
 Properties of Alkaloids
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
• QAS (R4-N) e.g. d-Tubocurarine
II- Basicity:
• R2-NH > R-NH2 > R3-N
• Saturated hexacyclic amines are more basic than aromatic amines.
 Properties of Alkaloids
Chemical Properties
• Based on basicity, alkaloids can be;
• Weak bases e.g. Caffeine
• Strong bases e.g. Atropine
• Amphoteric
• Phenolic alkaloids e.g. Morphine
• Alkaloids with Carboxylic groups e.g.
Narceine
• Neutral alkaloids e.g. Colchicine
Properties of Alkaloids
Chemical Properties
•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
 Properties of Alkaloids
Chemical Properties
• Stability
• Effect of heat:
• Alkaloids are decomposed by heat, except
Strychnine and Caffeine (sublimable).
• Reaction with acids:
• Salt formation
• Dilute acids hydrolyze Ester Alkaloids e.g.
Atropine
Properties of Alkaloids
Chemical Properties
•Dehydration
•Atropine → Apoatropine
•Morphine → Apomorphine
•Demethoxylation:
• e.g. Codeine
 Properties of Alkaloids
Chemical Properties
•Effect of Alkalis
•Dilute alkalis liberate most alkaloids from
their salts e.g. NH3.
•May cause isomerization (racemization) of
alkaloid e.g. conversion of hyoscyamine to
atropine.
•Can form salts with alkaloids containing a
carboxylic group e.g. Narceine.
 Properties of Alkaloids
Chemical Properties
• Effect of Alkalis (cont’d)
• Strong alkalis e.g. aqueous NaOH and KOH form
salts with phenolic alkaloids.
• Strong alkalis cause hydrolysis of Ester
alkaloids (e.g. atropine, cocaine and
physostigmine) and Amide alkaloids
(colchicines).
• Strong alkalis cause opening of lactone ring.
 Properties of Alkaloids
Chemical Properties
• 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)
Pharmacological Actions & Uses
•Effects of Alkaloids on Humans
•High biological activity
•Produce varying degrees of physiological
and psychological responses
•Largely by interfering with
neurotransmitters
•Others interfere with membrane
transport, protein synthesis or other
processes
Pharmacological Actions & Uses

•Effects of Alkaloids on Humans

•In large doses - highly toxic – fatal
•In small doses, many have
therapeutic value
•muscle relaxants, tranquilizers, pain
killers, mind altering drugs,
chemotherapy
Pharmacological Actions & Uses
• Psychoactive Alkaloids
• Although only a small percent are psychoactive,
these get much focus
• Affect the central nervous system - often by
influencing neurotransmitters
• Categories of psychoactive cmpds
• Stimulants
• Hallucinogens
• Depressants
• May also be narcotic (addictive)
Pharmacological Actions & Uses

Stimulants Hallucinogens Depressants

Cocaine Tropane alkaloids Morphine

Ephedrine Mescaline Codeine

Caffeine Psilocybin Heroin

Ergot alkaloids (LSD)

Pharmacological Actions & Uses
• Autonomic Nervous System:
• Sympathomimetics (ephedrine) or
sympatholytics (yohimbine, ergot alkaloids),
parasympathomimetics (pilocarpine),
anticholinergics (choline), ganglioplegics
(nicotine).
• Also, local anesthetics (cocaine), defibrillation (quinidine), anti-tumour
agents (ellipticine), anti-malarial (quinine), anti-bacterials (berberine), and
amoebicides (emetine).
 Chemical Tests for Alkaloids
• Most alkaloids are precipitated from neutral or slightly acidic solution by:
1. Mayer's reagent (potassiomercuric iodide solution)  Cream coloured
precipitate.
2. Dragendorff's reagent (solution of potassium bismuth iodide) orange
coloured precipitate.
3. Wagner’s reagent (iodine in potassium iodide)  red-brown precipitate
4. Hager's reagent (picric acid)  yellow precipitate
• Classification of Alkaloidal precipitating agents:
1- Reagents that form double salts:
a- Mayer’s Reagent: Potassium Mercuric Iodide.
b- Dragendorff’s Reagents: Potassium Iodobismethate.
c- Gold Chloride.
2- Reagents Containing Halogens:
a- Wagner’s Reagent: Iodine/ Potassium Iodide.
3-Organic Acids:
a- Hager’s Reagent: Picric Acid
b- Tannic Acid.
Classification of Alkaloidal precipitating
agents:
4- Oxygenated High Molecular Weight Acids:
a- Phosphomolybdic acid
b- Phosphotungestic acid
c- Silicotungestic Acid
Key Points

• Alkaloids are basic naturally occurring compounds containing one or

more nitrogen atoms usually in a heterocyclic ring and have a marked
physiological action on man or other animals
• Alkaloids are produced by a large variety of organisms, including
bacteria, fungi, plants, and animals and are part of the group of
natural products
• Alkaloids may occur in free state (e.g. as free bases), as salts (e.g.
with organic acids),