What are Alkaloids?
·
Alkaloids
are usually secondary metabolites.
·
The term
alkaloid was coined by Meissner in 1819. Alkaloids are “alkali like” substances / organic compounds.
·
They are basic nitrogen containing compound
obtained from plant, animal and microorganism having marked physiological
action.
·
They are
basic in nature; they contain one or more nitrogen atom (usually in
heterocyclic ring).
·
First synthesized alkaloid was connine.
Define the term Alkaloids.
Alkaloids are complex
organic compounds of natural or synthetic origin which are basic in nature and
contains one or more nitrogen atom, normally of heterocyclic nature and possess
specific pharmacological activity on human or animal body, when used in small
quantity.
Discuss the distribution of Alkaloids in the
plant kingdom?
·
Rare
in lower plants.
·
Dicots
are richer in alkaloids than Monocots.
·
Families
rich in Alkaloids: Apocynaceae, Rubiaceae, Solanaceae and Papaveraceae.
·
Families
free from Alkaloids: Rosaceae, Labiatae.
·
They
found in different parts of the plant:
ü
All
Parts e.g. Datura
ü
Barks
e.g. Cinchona
ü
Seeds
e.g. Nux vomica
ü
Roots
e.g. Aconite
ü
Fruits
e.g. Black pepper
ü
Leaves
e.g. Tobacco
ü
Latex
e.g. Opium
Name the different forms in which alkaloids
found in Plants.
— In
the form of Free bases e.g. Caffeine
— Salts
with Organic acids e.g. Oxalic, Acetic acid.
— Salts
with inorganic acids e.g. HCl, H2SO4
— Salts
with special acids: Meconic acid in Opiumin, Quinic acid in Cinchona.
— Glycosidal
form e.g. Solanine in Solanum.
Discuss the role / functions of Alkaloids in Plants.
Alkaloids
are doing following functions in the plants:
— They
may act as protective against insects and herbivores due to their bitterness
and toxicity.
— They
are, in certain cases, the final products of detoxification (waste products).
— As
a source of nitrogen in case of nitrogen deficiency.
— As
a Carrier: For transportation of different acids.
— They,
sometimes, act as growth regulators in certain metabolic systems.
— They
may be utilized as a source of energy in case of deficiency in carbon dioxide
assimilation.
Explain the various physical and chemical properties of the
alkaloids.
1. Physical
Properties
A.
Condition:
— Most
alkaloids are crystalline solids.
— Few
alkaloids are amorphous solids e.g. emetine.
— Some
are liquids that are either:
ü Volatile
e.g. nicotine and coniine.
ü Non-volatile
e.g. pilocarpine and hyoscine.
B.
Colour:
The
majority of alkaloids are colorless but some are colored e.g.: Colchicine and
berberine are yellow.
Canadine
is orange.
C.
Solubility:
— Both
alkaloidal bases and their salts are soluble in alcohol.
— Generally,
the bases are soluble in organic solvents and insoluble in water
Exceptions:
ü Bases
soluble in water: caffeine, ephedrine, codeine, colchicine, pilocarpine and
quaternary ammonium bases.
ü Bases
insoluble or sparingly soluble in certain organic solvents: morphine in ether,
theobromine and theophylline in benzene.
Salts
are usually soluble in water and, insoluble or sparingly soluble in organic
solvents.
Exceptions:
ü Salts
insoluble in water: Quinine monosulphate.
ü Salts
soluble in organic solvents: Lobeline and apoatropine hydrochlorides are
soluble in chloroform.
2. Chemical
Properties
·
Alkaloids are basic in nature (Lone pair
of electrons on nitrogen)
·
Basicity increased when adjacent
functional group are electron releasing.
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
·
Basicity order: R2-NH > R-NH2 > R3-N
·
Saturated hexacyclic amines are more basic
than aromatic amines.
·
Bases sensitive to decomposition whereas
salts are stable.
Isomerisation:
— Optically
active isomers may show different physiological activities.
— l-ephedrine
is 3.5 times more active than d-ephedrine.
— l-ergotamine
is 3-4 times more active than d-ergotamine.
— d-
Tubocurarine is more active than the corresponding l- form.
— Quinine
(l-form) is antimalarial and its d- isomer quinidine is antiarrhythmic.
— The racemic (optically inactive) dl-atropine
is physiologically active.
Give the general classification of Alkaloids?
There
are three main types of alkaloids: (1) true alkaloids, (2) protoalkaloids, and
(3) pseudoalkaloids. True alkaloids and protoalkaloids are derived from amino
acids, whereas pseudoalkaloids are not derived from these compounds.
A.
True Alkaloids
·
True alkaloids derive from amino acid
and they contain a heterocyclic ring with nitrogen.
·
These alkaloids are highly reactive
substances with biological activity even in low doses.
·
All true alkaloids have a bitter
taste and appear as a white solid, with the exception of nicotine which has a
brown liquid.
·
True alkaloids form water-soluble
salts.
·
Moreover, most of them are
well-defined crystalline substances which unite with acids to form salts. True
alkaloids may occur in plants (1) in the free state, (2) as salts and (3) as
N-oxides.
·
These alkaloids occur in a limited
number of species and families, and are those compounds in which decarboxylated
amino acids are condensed with a non-nitrogenous structural moiety.
·
The primary precursors of true
alkaloids are such amino acids as L-ornithine, L-lysine,
L-phenylalanine/L-tyrosine, L-tryptophan and L-histidine.
·
Examples of true alkaloids include such biologically active alkaloids as
cocaine, quinine, dopamine and morphine.
B.
Proto-alkaloids / Amino Alkaloids
·
Proto-alkaloids are compounds, in
which the N - atom derived from an amino acid and is not a part of the
heterocyclic.
·
They are derived from L-tyrosine and
L-tryptophan.
·
Proto-alkaloids are those with a
closed ring, being perfect but structurally simple alkaloids.
·
Examples: Ephedra, Colchicum etc.
C.
Pseudoalkaloids
·
Pseudoalkaloids are compounds, the
basic carbon skeletons of which are not derived from amino acids.
·
In reality, pseudoalkaloids are
connected with amino acid pathways. They are derived from the precursors or
post-cursors (derivatives the in-degradation process) of amino acids.
·
They can also result from the
amination and transamination reactions of the different pathways connected with
precursors or post-cursors of amino acids.
·
These alkaloids can also be derived
from non-amino acid precursors.
·
The N atom is inserted into the
molecule at a relatively late stage, for example, in the case of steroidal or
terpenoid skeletons.
·
Examples of pseudoalkaloids include such compounds as coniine, capsaicin,
ephedrine, solanidine, caffeine and theobromine.
Alkaloids
are mainly divided into two categories on the basis of their chemical
structure, that is, heterocyclic rings.
Atypical
alkaloids
These
are also known as nonheterocyclic alkaloids and contain nitrogen in aliphatic
chain.
Typical alkaloids
These
are also known as heterocyclic alkaloids and contain nitrogen in heterocyclic
ring system.
Discuss the classification of Alkaloids based on biosynthetic
origin.
Different metabolic pathways are involved in the biosynthesis of alkaloids. It is important to know precursor / starting material from
which the alkaloids in question are produced in the plant biosynthetically.
It is quite convenient and also logical to group together all
alkaloids having been derived from the same precursor but possessing different
taxonomic distribution and pharmacological activities.
Examples
(i)
Indole alkaloids derived from tryptophan.
(ii)
Piperidine alkaloids derived from lysine.
(iii)
Pyrrolidine alkaloids derived from ornithine.
(iv)
Phenylethylamine alkaloids derived from tyrosine.
(v)
Imidazole alkaloids derived from histidine.
It
is, however, pertinent to mention at this juncture that the enormous volume of
authentic information accumulated so far with regard to the isolation of alkaloids from
a variety of plant species and their subsequent characterization by the help of
latest analytical techniques they may be classified as follows:
A. Alkaloids
derived from Amination Reactions
(i)
Acetate-derived Alkaloids
(ii)
Phenylalanine-derived Alkaloids
(iii)
Terpenoid Alkaloids
(iv)
Steroidal Alkaloids
B. Alkaloids
derived from Anthranilic Acid
(i)
Quinazoline Alkaloids
(ii)
Quinoline Alkaloids
(iii)
Acridine Alkaloids
C. Alkaloids
derived from Histidine
Imidazole
Alkaloids
D. Alkaloids
derived from Lysine
(i)
Piperidine Alkaloids
(ii)
Quinolizidine Alkaloids
(iii)
Indolizidine Alkaloids
E. Alkaloids
derived from Nicotinic Acid
Pyridine
Alkaloids
F. Alkaloids
derived from Ornithine
(i)
Pyrrolidine Alkaloids
(ii)
Tropane Alkaloids
(iii)
Pyrrolizidine Alkaloids
G. Alkaloids
derived from Tyrosine
(i)
Phenylethylamine Alkaloids
(ii)
Simple Tetrahydro iso-quinoline Alkaloids
(iii)
Modified Benzyl Tetrahydro iso-quinoline Alkaloids
H. Alkaloids
derived from Tryptophan
(i)
Simple Indole Alkaloids
(ii)
Simple b-Carboline Alkaloids
(iii)
Terpenoid Indole Alkaloids
(iv)
Quinoline Alkaloids
(v)
Pyrroloindole Alkaloids
(vi)
Ergot Alkaloids
Discuss the classification of Alkaloids based on their major pharmacological
activity.
Interestingly,
the alkaloids exhibit a broad range of very specific
pharmacological characteristics. Perhaps this might also be used as a strong
basis for the general classification of the wide-spectrum of alkaloids derived
from the plant kingdom, such as: analgesics, cardio-vascular drugs,
CNS-stimulants and depressants, dilation of pupil of eye, mydriatics,
anticholinergics, sympathomimetics, antimalarials, purgatives, and the like.
However, such a classification is not quite common and broadly known.
Examples
(i) Morphine as
Narcotic analgesic;
(ii) Quinine as
Antimalarial;
(iii) Strychnine as
Reflex excitability;
(iv) Lobeline as
Respiratory stimulant;
(v) Boldine as
Choleretics and laxatives;
(vi) Aconitine as
Neuralgia;
(vii) Pilocarpine as
Antiglaucoma agent and miotic;
(viii) Ergonovine as
Oxytocic;
(ix) Ephedrine as
Bronchodilator;
(x) Narceine as
Analgesic (narcotic) and antitussive.
The
extraction of alkaloids is based on their basic character and solubility
profiles. Generally, alkaloids are extracted mainly using two methods.
1. Stass-Otto
Method
- The powdered material that contains alkaloidal salts is moistened with alkaline substances like sodium bicarbon-ate, ammonia, calcium hydroxide, etc., which combines with acids, tannins and other phenolic substances and sets free the alkaloids bases.
- Extraction is then carried out with organic solvents such as ether or petroleum spirit.
- The concentrated organic liquid is then shaken with aqueous acid and allowed to separate.
- Alkaloid salts will be present in aqueous liquid, while many impurities remain behind in the organic liquid.
- The collected powdered material is extracted with water or aqueous alcohol containing dilute acid.
- Chloroform or other organic solvents are added and shaken to remove the pigments and other unwanted materials.
- The free alkaloids are then precipitated by the addition of excess alkalis like, sodium bicarbonate or ammonia and separated by filtration or by extraction with organic solvents.
Volatile
liquid alkaloids (nicotine and coniine) are isolated by distillation. The
powdered material that contains alkaloids is extracted with water and the
aqueous extract is made alkaline with sodium carbonate or ammonia and the
alkaloid is distilled off in steam. This could be collected and purified.
Discuss the general chemical tests used for the identification of Alkaloids.
The chemical tests
are performed from neutral or slightly acidic solution of drug.
Dragendorff’s
Test
Drug solution
+ Dragendroff’s reagent (Potassium Bismuth Iodide), formation of Orange- red
colour.
Mayer’s
Test
Drug solution
+ few drops of Mayer’s reagent (potassium mercuric iodide), formation of
creamy-white precipitant.
Hager’s
Test
Drug solution
+ few drops of Hagers reagent (Saturated aq. Solution of Picric acid),
formation of crystalline yellow precipitate.
Wagner’s
Test
Drug solution
+ few drops of Wagner’s reagent (dilute Iodine solution), formulation of
reddish-brown precipitate.
Tannic
Acid Test
Drug solution
+ few drops of tannic acid solution, formation of buff coloured precipitate.
Ammonia
Reineckate Test
Drug solution
+ slightly acidified (HCl) saturated solution of ammonia reineckate, formation
of pink flocculent precipitate.
