Alkaloids

By

Dr. Huda Saaran

Lab no. One
Baghdad college of Pharmacy
❖ Definition

❖ Alkaloids are basic nitrogen containing compounds.

❖ They are generally obtained from plants, animals and microorganisms

and often demonstrate a marked physiological action.

❖ The name alkaloid (“alkali-like”) was originally applied to the substances

because, like the inorganic alkalis, they react with acids to form salts
• ALKALOID DESCRIPTION

➢ Naturally occurring chemical compounds containing basic nitrogen atoms, usually extracted from
an amino acid.
➢ Bitter tasting, generally white solids (exception -nicotine is a brow liquid).
➢ They give a precipitate with heavy metal iodides.
➢ Insoluble or sparingly (moderately)soluble in water.
➢ Caffeine (a purine derivative) does not precipitate like most alkaloids.
➢ Alkaloids are basic - they form water soluble salts. Most alkaloids are well-defined crystalline
substances, which unite with acids to form salts.

➢ In plants, they may exist

 In the free state,
 as salts, or
 as N-oxides.
➢ Occur in a limited number of plants. Nucleic acid exists in all plants, where as Morphine exists in
only one plant species.

➢ Usually classified according to the nature of the basic chemical structures from which they are
derived.
 OCCURRENCE, DISTRIBUTION& LOCATION OF ALKALOIDS

➢ Occur in bacteria(Pseudomonas aeruginosa) and rarely in fungi (psilocin from

hallucinogenic mushrooms).

➢ Some alkaloids occur in several genera (group) from different species (caffeine),
but most occur in closely related species.

➢ Some occur in certain families (hyoscyamine), while others occur only in a specific
species (morphine).

➢ Rarely do plants contain more than 1 type of alkaloid.

➢ All alkaloids of one plant will have a common biogenetic origin.

Distribution

• Alkaloids occur in all plant parts, but are usually

localized in one organ (e.g.the bark or seeds).

• Within the plant, [alkaloid] can vary widely from part to

part –some parts may contain no alkaloids.

• Occasionally, different alkaloids also form in different

parts of the plant.

• Alkaloid concentrations occur in wide ranges –e.g.

Madagascar periwinkle contains 3g per (anti cancer) alkaloids
per ton of leaves.
NAMING OF ALKALOIDS

Numerous methods can be used to name alkaloids

1-Generic plant name –atropine from Atropa belladonna.
2-Specific name of the plant –cocaine from Erythroxylum coca.
3-Common name of the herb –ergotamine from ergot (rye).
4-Physiological action of the plant –emetine producing emesis.
5-Other –e.g. morphine derived from ancient Greek mythology –Morpheus
–god of dreams.
6- A prominent physical character, such as Hygrine that is hygroscopic.
Classification of Alkaloids :
1. Biological origin

Sedatives : Morphine.

Vasodilatation : Ephedrine, Ergonovine.

Local anesthetic : Cocaine.

Hallucinating : Mescaline, Psilocybin.

2- Biosynthetic pathway

Common amino acid precursors:

• Phenylalanine
• Tyrosine
• Tryptophan
• Histidine
• Anthranilic acid
• Lysine
• Ornithine
3- Chemical classification

➢ True (Typical) alkaloids that are derived from amino acids and have
nitrogen in a heterocyclic ring. e.g. Atropine

➢ Proto alkaloids 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.
A. Proto alkaloids
➢ These are also called Non heterocyclic or Atypical alkaloids or Biological amines.

➢ These are less commonly found in nature.

➢ These molecules have a nitrogen atom which is not a part of any ring system.

➢ Examples of these include ephedrine, colchicine, erythromycin and Taxol etc.

B. Heterocyclic Alkaloids or Typical Alkaloids:

➢ Structurally these have the nitrogen as a part of a cyclic ring system.

➢ These are more commonly found in nature.

➢ Heterocyclic alkaloids are further subdivided into 14 groups based on the ring structure
containing the nitrogen
4- Classification based on the ring structure or nucleus
of the chief alkaloid group in the plant drug:
- Pyridine-Piperidine.
- Tropane.
- Quinoline.
- Isoquinoline.
- Indole.
- Imidazole.
- Steroid.
- Alkaloidal amines.
- Purine.
 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.
• The salts of sanguinarine are copper-red.
III- Solubility:
• Soluble in polar and organic solvent
• In soluble in water
• Salts are usually soluble in water and, insoluble or sparingly
soluble in organic solvents.
IV- Isomerization:
Optically active isomers may show different
physiological activities.
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. Conc. acids may cause:
• Dehydration:
Atropine → Apoatropine
Morphine → Apomorphine
• Demethoxylation:
e.g. Codeine.
❖ Important general reactions involved:

-Decarboxylation
The process of removing a carboxyl group from a chemical compound.

-Transamination
The process of transposing an amino group within a chemical compound.
 The basicity of alkaloids depends on the availability of the lone pair of
e-on the N2 atoms: e-donating groups enhance basicity, while e-
withdrawing groups decrease it.
 Because some alkaloids have a carbonyl group on the amide, they can
also be neutral (colchicine & piperine).
 Basic characteristic renders complex alkaloids unstable, so that in
solution they are sensitive to heat, light & oxygen.
 Basic character of alkaloids also allows them to form salts with mineral
acids (such as hydrochlorides, nitrates and sulphates) or inorganic acids
(tartrates, sulfamates).
 Alkaloid salts are soluble in water and dilute alcohols.
 Solid salts can be conserved well and are a common.
TESTS FOR ALKALOIDS
 Most alkaloids are precipitated from neutral or slightly acidic
solution by
 Dragendorff's reagent (solution of potassium bismuth
iodide)orange coloured precipitate.
 Mayer's reagent (potassio mercuric iodide solution) Cream
coloured precipitate.
 Wagner’s reagent (iodine in potassium iodide)
red-brown precipitate.
 Hagers reagent (picric acid) yellow precipitate.
 Caffeine does not precipitate.
EXTRACTION OF ALKALOIDS
➢ Extraction is based on the basicity of alkaloids and on the fact that they normally
occur in plants as free bases, salt, or an oxide.
➢ Herbs often contain other materials which can interfere with extraction such as large
amounts of fat, waxes, terpenes, pigments and other lipophilic substances (e.g. by
forming emulsions) –avoided by defatting the crushed herb (using petroleum ether
and hexane).
➢ Extraction method normally depends on the raw material, the purpose
of extraction & the scale on which is to be performed.
➢ For research purposes: chromatography allows for quick and reliable results.

➢ If larger amounts of alkaloids need to be extracted, one of the following methods

can be used.
GENERAL METHOD
Step I
➢ Powdered, defatted herb is mixed with an alkaline
aqueous solution.
➢ Free bases are then extracted with organic
solvents.
➢ Normally aqueous ammonia is used, but a
carbonate solution is used when alkaloids contain
fragile elements such as a ester
or lactone.
➢ In some cases, e.g. Cinchona bark, a mixture of
calcium hydroxide & sodium hydroxide should be
used as the alkaloids
are bound to tannins.
➢ Organic solvent: chloroform, dichloromethane or
ethyl acetate –depends on the polarity of the
compound present in the mixture.
Step II

➢ Organic solvent containing alkaloids (bases) is

separated from residue & concentrated by
distillation under pressure if needed.

➢ Solvent is stirred with an acidic aqueous

solution: alkaloids go into the solution as salts.
Impurities remain in the organic phase.
• Aqueous solution of alkaloid salts is washed with
a non- polar solvent (hexane).

• Alkalinized with a base using an organic solvent

not miscible with water.

• Alkaloids precipitate and dissolve in the organic

phase.

• Extraction of aqueous phase continues till all

alkaloids have moved into the organic phase
(tested when Mayer’s reaction on the aqueous
phase becomes negative).

• This purification step may be carried out in a

separation funnel or in centrifugal extractors.
Step III

➢ Organic solvent containing

alkaloid bases is decanted, freed
from water traces (drying over
anhydrous salt e.g. sodium
sulphate) and evaporated under
reduced pressure.

➢ A dry residue remains: total basic

alkaloids.
Extraction of liquid alkaloids 2 Methods possible

1- Plant powder is extracted directly with

acidified water.

2- Plant powder is extracted with acidified

alcoholic or a hydroalcoholic solution. This is
then followed by distillation under vacuum
(eliminates that alcohol, leaving behind and
acidic aqueous solution of alkaloid salts)
THE END