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
anti-
malaria
anti-
aritmia .
 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 caffeine synthase / N-methyltransferase

theobromine 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
hexane)
 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 ion-
exchange 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