ALKALOIDA

Siti Rofida

Alkaloids: Introduction
small organic molecules (secondary metabolites) of
plants which contain nitrogen (ussually in a ring)
alkaloids, protoalkaloids, pseudoalkaloids
structurally diverse: 12,000+ structures
20% of all plant species
concentrated in specific plant taxa (families, genera,
species)
biosynthetically diverse (families/types)
strong biological effects (-> 3 ecological examples)

Historical and human importance:

pharmaceutically significant (often neurological)
effect of N
biological effects & uses:
analgesic - pain killers (morphine)
paralysis, anesthesia (tubocurarine, coniine)
stimulants (caffeine, nicotine)
antitussive (codeine)
emetic (emetine)
anti-cancer drugs (taxol, vinblastine)
toxins and antibiotics (quinine, sanguinarine)

Alkaloid Families and Biosynthesis

families classified by ring structure

derived from amino acids
Examples:
tyrosine -> morphine (opium alkaloids)
tryptophan -> quinine (quinoline)
vinblastine (indole)
glutamate (via ornithine) -> cocaine (tropane)
- >nicotine (tobacco alk)
- > senecionine (pyrrollizidine)
aspartate -> nicotine
xanthine -> caffeine, theobromine (purine)

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

Terpenoid Indole Alkaloids

antikanker
antimalaria
antiaritmia .

Benzylisoquinoline Alkaloids
Analgesik,
gout,
blocker neuromuskuler
antimikroba

Tropane Alkaloids and

Nicotine
Familia Solanaceae
antikolinergik

Purine Alkaloids
Xanthosine
N-methylations

7-methylxanthosine
N-methylations

caffeine synthase / N-methyltransferase

7-methylxanthine,
N-methylations

theobromine

caffeine synthase / N-methyltransferase

caffeine

Tests for Alkaloids

Most alkaloids are precipitated from neutral or
slightly acidic solution by
Mayer's reagent (potassiomercuric iodide
solution) Cream coloured precipitate.
Dragendorff's reagent (solution of potassium
bismuth iodide) orange coloured precipitate.
Wagners reagent (iodine in potassium iodide)
red-brown precipitate
Hagers reagent (picric acid) yellow
precipitate
Caffeine does precipitate

Extraction of Alkaloids
Extraction is based on the basicity of
alkaloids and on the fact that they
normally occur in plants as salts (i.e.:
on the solubility of bases and salts in
water and organic solvents).
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

Extraction in an Alkaline
Medium
Step 1: Powdered, defatted
herb is mixed with an
alkaline aqueous solution.

This displaced alkaloids from their salt combinations.

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 toxicity, safety, cost
& ease of recovery and recycling of the solvent).

The Soxhlet Apparatus

Industry: uses solid-liquid
extractors based on the
principle of counter-current
extraction, such Soxhlet
apparatus.

Extraction of Alkaloids: 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.
Repeated until the organic
phase no longer contains
alkaloids.
Many acids can be used (HCL,
Sulfuric, citric, tartaric), but
always in very dilute
concentrations (1-5%)

Alkaloid Extraction: Step III

Aqueous solution of alkaloid salts is
washed with an apolar 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 Mayers reaction on
the aqueous phase becomes
negative).
This purification step may be carried
out in a separation funnel or in
centrifugal extractors.
Separation Funnel

Final Step
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.

Kava Powder

Alkaloid Extraction in Acidic

Medium
2 Methods possible
Pulverized drug is extracted
directly with acidified
water
Or
Pulverized drug 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)

Vacuum Distillation

In both cases: Results = aqueous solution of

alkaloid salts needing purification.
Purification achieved by
Alkalinizing solution & extracting bases with
an immiscible organic solvent.
Selectively absorb the alkaloids contained in
the solution on an ion exchange resin, then
eluting them with a strong acid.
Precipitating the alkaloids as
iodomercurates. The resulting alkaloids are
recovered by filtration, dissolved in a mixture
of water, alcohol and acetone and
decomposed by passing through an ionexchange resin.

Isolation of Alkaloids
All methods of alkaloid
extraction yield
impure compounds, so
alkaloids therefore
have to be separated.
TLC and HPLC are most
commonly used.
Under the best
conditions, alkaloids
can be obtained by
direct crystallization:
simply by neutralizing
the acidic extraction
medium.

Crystals of Hydrastine