introduction, identification, classification, therapeutic action of alkaliods

1. Alkaloids

2. Definition
 Alkaloids are basic nitrogen containing
compounds. They are generally obtained from
plants, animals and microorganisms and
often demonstrate a marked physiological action

3. ALKALOID DESCRIPTION
 Contains nitrogen -usually derived from an amino acid.
 Bitter tasting, generally white solids (exception -nicotine is a brown
liquid).
 They give a precipitate with heavy metal iodides.
 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, whereas, morphine exists in only one plant species .

4. 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 precipitate

5. OCCURRENCE, DISTRIBUTION& LOCATION OF
ALKALOIDS
 Occur in bacteria(Pseudomonas aeruginosa) and
rarely in fungi (pscilocin from hallucinogenic
mushrooms).
 Some alkaloids occur in several genera 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
biogenenetic origin

7. • 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)

8. PHYSICAL-CHEMICAL PROPERTIES OF ALKALOIDS
 MW: 100 –900
 Most bases which do not contain O2 are liquid at
room temperature (nicotine), while those that do are
solids. In rare cases they are coloured.
 Most solid bases rotate the plane of polarized
light, have high melting points.
 Normally are not soluble in water (occasionally
slightly soluble).
 Soluble in a polar or slightly polar organic solvents.
Soluble in concentrated hydroalcoholic solutions

9.  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.

10. 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

11. 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 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.

12. GENERAL METHOD
• 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

13. 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.

14. • 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 Mayer’s reaction
on the aqueous phase
becomes negative).
• This purification step may be
carried out in a separation
funnel or in centrifugal

15.  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.

16. 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)

17. Classification of
Alkaloids
1. Biological origin
Sedatives : Morphine
Vasodilatation : Ephedrine, Ergonovine
.
Local anesthetic : Cocaine
Hallucinating : Mescaline, Psilocybin.

18. 2-Biosynthetic pathway
Ornithine- Tropane, Pyrrolidine, Pyrrolizidine
Tyrosine-Benzyl isoquinoline
Tryptophane- Indole alkaloids, Quinoline
Pyridine- Pyridine
Lysine- Quinolizidine, Piperidine

19. 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.

20. 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.
 Table below shows the chemical structure and
biological significance of these compounds:

21. Name Structure
Biological
Significance
Ephedrine
Adrenergic agent-
used for asthma and
hay fever
Colchicine Relieves gout
Erythromycin Antibiotic

22. Taxol
(Paclitaxel)
Used in the treatment
of ovarian cancer,
breast cancer and
non-small cell lung
cancer

23. 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

24. No. Heterocycle Example
1.
Pyrrole and
Pyrrolidine
Hygrine, Stachydrine
2.
Pyrrolizidine
Senecionine, Symphitine, Echimidine,
Seneciphylline

25. 3.
Pyridine and Piperidine
Lobeline, Nicotine, Piperine, Conine,
Trigonelline
4.
Tropane (piperidine/N-methyl-
pyrrolidine)
Cocaine, Atropine, Hyoscyamine, Hyoscine
5.
Quinoline
Quinine, Quinidine, Cinchonine,
Cinchonidine

26. 6.
Isoquinoline
Morphine, Emetine, Papaverine, Narcotine,
Tubocurarine, Codeine
7.
Aporphine (reduced
isoquinoline/naphthalene)
Boldine
8.
Quinolizidine
Lupanine, Cytisine, Laburnine, Sparteine

27. 9.
Indole or
Benzopyrole
Ergometrine, Vinblastine, Vincristine, Strychnine, Brucine,
Ergotamine, Yohimbine, Reserpine, Serpentine,
Physostigmine
10.
Indolizidine
Castanospermine, Swainsonine
11.
Imidazole or
glyoxaline
Pilocarpine, Pilosine

28. 12.
Purine (pyrimidine/imidazole)
Caffeine, Theobromine
13.
Steroidal (some combined as
glycosides)*
Conessine, Solanidine
14. Terpenoid*
Aconitine, lycaconitine, Aconine
*Note- Steroidal and terpenoid classes are also treated as separate classes or along with glycosides.