Alkaloids

Alkaloids
Mr. Vishal Suresh Bagul
S.Y.M.Pharmacy
Department of Pharmacogony
R.C.Patel Institute of Pharmaceutical Eduction & Research ,Shipur

Definition
• Alkaloids are basic nitrogen containing
compounds. They are generally obtained
from plants, animals and microorganisms
and often demonstrate a marked
physiological action
Mr.Vishal S Bagul Department of Pharmacognosy,RCPIPER,Shipur

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.
• Biosynthesis: Some alkaloids are not derived from amino
acids e.g purine, steroidal alkaloid .

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 .

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

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

• 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 tonne of leaves.

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

• 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
commercial form of alkaloids.

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

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.

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 toxicity, safety, cost
& ease of recovery and recycling of
the solvent).Mr.Vishal S Bagul Department of Pharmacognosy,RCPIPER,Shipur

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 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
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)

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

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

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

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

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

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

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

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

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

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

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.

Biosynthetic classification
1. Ornithine derived alkaloids
e.g. Pyrrolidine alkaloid-nicotine
Tropane alkaloid – Atropine, hyosyamine, coacaine
2. Lysine derived alkaloids
e.g. Piperidine and pyridine alkaloid – conine, lobaline, arecoline
Quinazolidine alkaloid- lupinine
3. Tyrosine derived alkaloids
e.g. Isoquinoline alkaloid – morphine, codeine, emetine, cephaline, berberine, d- tubocurine
Amino alkaloid- colchicine
4. Tryptophan derived alkaloids
e.g. Indole alkaloid- ergot alkaloid, vincristine, vinblastine, reserpine, strychnine,
physostigmine, strychinine, brucine
Quinoline alkaloid – cinchonine, quinine, quinidine, camptothecin
5. Histidine derived alkaloids
e.g. Imidazole alkaloid – Pilocrpine
6. Phenylalanine derived alkaloids
e.g. Amino alkaloid- Ephedrine

Pharmacological classification
1. Narcotic analgesic e.g.Morphine
2. Antimalerial e.g. Quinine
3. Reflux excitability e.g.Strychnine
4. Respiratory stimulant e.g.Lobeline
5. Neuralgia e.g. Aconitine
6. Oxytocic e.g. Erogotometrine
7. Bronchodilator e.g. Ephedrine, vasicine
8. Anticholinergic e.g. Atropine
9. CNS stimulant e.g. Caffeine
10. Antitussive e.g. Codeine
11. Antiarrythmic e.g.Quinidine
12. Antihypertensive e.g. Reserpine
13. Anticancer e.g. Vincristine
14. Antiglucoma e.g. Pilocarpine

Biosynthesis of indole alkaloids

Biosynthesis of Isoquinoline alkaloids

Biosynthesis of Tropane alkaloids

Biosynthesis of Quinoline alkaloids

Alkaloids

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Viewers also liked

Viewers also liked (8)

Similar to Alkaloids

Similar to Alkaloids (20)

More from Vishal Bagul

More from Vishal Bagul (8)

Recently uploaded

Recently uploaded (20)

Alkaloids