Alkaloids
Defination
These are the organic products of natural or synthetic origin which are basic in nature & contain one or more than one nitrogen atoms, normally of heterocyclic nature & possess specific physiological actions on human or animal body, when used in small quantites.
The term is derived from the word ‘alkali-like’ & hence they resemble some of characters of naturally occuring amin
New Definition:
Alkaloids are cyclic organic compounds containing nitrogen in a negative state of oxidation with limited distribution among living organisms.
Types Of Alkaloids
*True Alkaloids
*Proto Alkaloids
*Pseudo Alkaloids
TRUE ALKALOIDS:These contain heterocyclic nitrogen, which is derived from amino acids & always basic in nature. These alkaloids are toxic & normally present in plants as salts of organic acids e.g. Morphine, Codeine
PROTO ALKALOIDS:These are simple amines in which the nitrogen is not in heterocyclic ring. These are basic in nature & prepared in plants from amino acids e.g. Colchicine, Ephedrine
PSEUDO ALKALOIDS: These includes mainly steroidal, terpenoid alkaloids & purines. These are not derived from amino acids.
These do not show many of the typical characters of alkaloids but give the standard qualitative tests for alkaloids. e.g. caffeine
Occurrence
Alkaloids occurs in plants both in free form and salts of organic acids such as muconic acid, quinic acid, maleic, citric, oxalic acid. Salts with inorganic acids e.g. HCl, H2SO4.
Amongst Angiosperms, Leguminosae, Papaveraceae, Ranunculaceae, Solanaceae, Liliaceae are plant families for yeilding alkalloids.
Distribution
They are reported to be present in different parts of the plant and can be isolated from:
Seeds: Nux vomica, areca
Fruits: black pepper
Leaves: belladonna, vasaka, datura
Rhizomes and roots: ipecac, aconite,rauwolfia
Stems: ephedra
Bark: kurchi, cinchona
Fungi: ergot
Phusical Properties
With few exceptions, all the alkaloids are colourless, crystalline solids with a sharp melting point.
Some of the alkaloids are amorphous gums, while other are liquid & volatile in nature.
Some alkaloids are coloured in nature e.g. berberine is yellow.
Free bases of alkaloids are soluble in organic, non-polar, immiscible solvents.
The salts of most bases are soluble in water.
Free bases are insoluble in water.
The alkaloids containing quarternary bases are only water soluble.
Some of pseudoalkaloids & protoalkaloids show higher solubility in water e.g. caffeine is freely soluble in water.
Isomerism: 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 antiarrythmic.
The racemic (optically inactive) dl-atropine is physiologically active.
Chemical Properties
Most of the alkaloids are basic in reaction, due to the availability of lone pair of electrons on nitrogen.
The basic character of the alkaloid is enhanced if the adjacent functional groups are electron releasing.
The alkaloid turns to be neutral or acidic when the adjacent functional groups are electron withdrawing like amide group which reduces the availability of the lone pair of electrons.
Alkaloids exhibiting basic character are very much sensitive to decomposition & cause a problem during storage their salt formation.
The alkaloids may contain one or more no. of nitrogen. It may exist in the form as
Primary amine (R-NH2) e.g. mescaline
Secondary amine (R2-NH) e.g. ephedrine
Tertiary (R3-N) e.g.atropine
Quartanary ammonium compounds e.g.tubocurarine hydrochloride
Basicity
R2-NH > R-NH2 > R3-N
Saturated hexacyclic amines is more basic than aromatic amines.
Stability
Effect of heat:
Alkaloids are decomposed by heat, except Strychnine and caffeine (sublimable).
Reaction with acids:
1- Salt formation.
2- Dil acids hydrolyze Ester Alkaloids e.g. Atropine
Chemical Tests For Alkaloids
*MAYER’S REAGENT Cream coloured ppt.
(pot. mercuric iodide solution)
*DREGENDORFF’S REAGENT Reddish brown ppt.
(pot. bismuth iodide solution)
*WAGNER’S REAGENT Reddish brown ppt.
(iodine-pot.iodide solution)
*HAGER’S REAGENT Yellow coloured ppt.
(picric acid solution)
*Tannic acid test: ppt soluble in dilute acid or ammonia solution
5%w/v aqs solution
of tannic acid
*Ammonia Reineckate Test: Pink flocculent ppt
(Ammonia Reineckate aqs solution)
General Isolation Procedure for Alkaloids
Purification of crude extract of Alkalloids
Direct crystallization from solvent
Steam distillation
Chromatographic techniques
pH gradient technique
ROLE OF ALKALOIDS IN PLANTS
They are reserve substances with an ability to supply nitrogen.
They might be the defensive mechanisms for plants growing in dry regions to protect from grazing animals, herbivores & insects.
They might have a possible role as growth regulatory factors in the plants.
These are end products of detoxification mechanisms in plants.
These are present in conjugation with the plant acids such as meconic acid hence acting as carriers within the plants for transportation of such acids.
Reservoirs of protein sythesis
PHARMACOLOGICAL ACTIVIES OF ALKALOIDS
Anticancer e.g. vinca
Hypotensive e.g. rauwolfia
Oxytocic e.g. ergot
Narcotic analgesic e.g. opium
Anticholinergic e.g. belladona, datura
Local anasthetic e.g. coca
Antimalarial e.g. cinchona
Expectorant e.g. vasaka
Biosynthesis of alkalloids
Most alkaloids are synthesized from a few common amino acids (tyrosine, tryptophan, ornithine or argenine, aspartic acid, & lysine)
Nicotinic acid precursor for part of nicotine
Purine precursor for caffeine
Some alkaloids synthesized from terpenes - along mevalonic acid pathway
Generally classified by the predominant ring structure and/or carbon skeleton
CHEMICAL CLASSIFICATION OF ALKALOIDS
PSEUDO ALKALOIDS
DITERPENES
e.g. Aconitine, aconine, hypoaconitine
PROTO ALKALOIDS
ALKYLAMINES
e.g. Ephedrine,pseudoephedrine, colchicine
Prefixes and suffixes:
Prefixes:
"Nor-" designates N-demethylation or N-demethoxylation, e.g. norpseudoephedrine and nornicotine.
"Apo-" designates dehydration e.g. apomorphine.
"Iso-, pseudo-, neo-, and epi-" indicate different types of isomers.
Suffixes:
"-dine" designates isomerism as quinidine and cinchonidine.
"-ine" indicates, in case of ergot alkaloids, a lower pharmacological activity e.g. ergotaminine is less potent than ergotamine.
Defination
These are the organic products of natural or synthetic origin which are basic in nature & contain one or more than one nitrogen atoms, normally of heterocyclic nature & possess specific physiological actions on human or animal body, when used in small quantites.
The term is derived from the word ‘alkali-like’ & hence they resemble some of characters of naturally occuring amin
New Definition:
Alkaloids are cyclic organic compounds containing nitrogen in a negative state of oxidation with limited distribution among living organisms.
Types Of Alkaloids
*True Alkaloids
*Proto Alkaloids
*Pseudo Alkaloids
TRUE ALKALOIDS:These contain heterocyclic nitrogen, which is derived from amino acids & always basic in nature. These alkaloids are toxic & normally present in plants as salts of organic acids e.g. Morphine, Codeine
PROTO ALKALOIDS:These are simple amines in which the nitrogen is not in heterocyclic ring. These are basic in nature & prepared in plants from amino acids e.g. Colchicine, Ephedrine
PSEUDO ALKALOIDS: These includes mainly steroidal, terpenoid alkaloids & purines. These are not derived from amino acids.
These do not show many of the typical characters of alkaloids but give the standard qualitative tests for alkaloids. e.g. caffeine
Occurrence
Alkaloids occurs in plants both in free form and salts of organic acids such as muconic acid, quinic acid, maleic, citric, oxalic acid. Salts with inorganic acids e.g. HCl, H2SO4.
Amongst Angiosperms, Leguminosae, Papaveraceae, Ranunculaceae, Solanaceae, Liliaceae are plant families for yeilding alkalloids.
Distribution
They are reported to be present in different parts of the plant and can be isolated from:
Seeds: Nux vomica, areca
Fruits: black pepper
Leaves: belladonna, vasaka, datura
Rhizomes and roots: ipecac, aconite,rauwolfia
Stems: ephedra
Bark: kurchi, cinchona
Fungi: ergot
Phusical Properties
With few exceptions, all the alkaloids are colourless, crystalline solids with a sharp melting point.
Some of the alkaloids are amorphous gums, while other are liquid & volatile in nature.
Some alkaloids are coloured in nature e.g. berberine is yellow.
Free bases of alkaloids are soluble in organic, non-polar, immiscible solvents.
The salts of most bases are soluble in water.
Free bases are insoluble in water.
The alkaloids containing quarternary bases are only water soluble.
Some of pseudoalkaloids & protoalkaloids show higher solubility in water e.g. caffeine is freely soluble in water.
Isomerism: 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 antiarrythmic.
The racemic (optically inactive) dl-atropine is physiologically active.
Chemical Properties
Most of the alkaloids are basic in reaction, due to the availability of lone pair of electrons on nitrogen.
The basic character of the alkaloid is enhanced if the adjacent functional groups are electron releasing.
The alkaloid turns to be neutral or acidic when the adjacent functional groups are electron withdrawing like amide group which reduces the availability of the lone pair of electrons.
Alkaloids exhibiting basic character are very much sensitive to decomposition & cause a problem during storage their salt formation.
The alkaloids may contain one or more no. of nitrogen. It may exist in the form as
Primary amine (R-NH2) e.g. mescaline
Secondary amine (R2-NH) e.g. ephedrine
Tertiary (R3-N) e.g.atropine
Quartanary ammonium compounds e.g.tubocurarine hydrochloride
Basicity
R2-NH > R-NH2 > R3-N
Saturated hexacyclic amines is more basic than aromatic amines.
Stability
Effect of heat:
Alkaloids are decomposed by heat, except Strychnine and caffeine (sublimable).
Reaction with acids:
1- Salt formation.
2- Dil acids hydrolyze Ester Alkaloids e.g. Atropine
Chemical Tests For Alkaloids
*MAYER’S REAGENT Cream coloured ppt.
(pot. mercuric iodide solution)
*DREGENDORFF’S REAGENT Reddish brown ppt.
(pot. bismuth iodide solution)
*WAGNER’S REAGENT Reddish brown ppt.
(iodine-pot.iodide solution)
*HAGER’S REAGENT Yellow coloured ppt.
(picric acid solution)
*Tannic acid test: ppt soluble in dilute acid or ammonia solution
5%w/v aqs solution
of tannic acid
*Ammonia Reineckate Test: Pink flocculent ppt
(Ammonia Reineckate aqs solution)
General Isolation Procedure for Alkaloids
Purification of crude extract of Alkalloids
Direct crystallization from solvent
Steam distillation
Chromatographic techniques
pH gradient technique
ROLE OF ALKALOIDS IN PLANTS
They are reserve substances with an ability to supply nitrogen.
They might be the defensive mechanisms for plants growing in dry regions to protect from grazing animals, herbivores & insects.
They might have a possible role as growth regulatory factors in the plants.
These are end products of detoxification mechanisms in plants.
These are present in conjugation with the plant acids such as meconic acid hence acting as carriers within the plants for transportation of such acids.
Reservoirs of protein sythesis
PHARMACOLOGICAL ACTIVIES OF ALKALOIDS
Anticancer e.g. vinca
Hypotensive e.g. rauwolfia
Oxytocic e.g. ergot
Narcotic analgesic e.g. opium
Anticholinergic e.g. belladona, datura
Local anasthetic e.g. coca
Antimalarial e.g. cinchona
Expectorant e.g. vasaka
Biosynthesis of alkalloids
Most alkaloids are synthesized from a few common amino acids (tyrosine, tryptophan, ornithine or argenine, aspartic acid, & lysine)
Nicotinic acid precursor for part of nicotine
Purine precursor for caffeine
Some alkaloids synthesized from terpenes - along mevalonic acid pathway
Generally classified by the predominant ring structure and/or carbon skeleton
CHEMICAL CLASSIFICATION OF ALKALOIDS
PSEUDO ALKALOIDS
DITERPENES
e.g. Aconitine, aconine, hypoaconitine
PROTO ALKALOIDS
ALKYLAMINES
e.g. Ephedrine,pseudoephedrine, colchicine
Prefixes and suffixes:
Prefixes:
"Nor-" designates N-demethylation or N-demethoxylation, e.g. norpseudoephedrine and nornicotine.
"Apo-" designates dehydration e.g. apomorphine.
"Iso-, pseudo-, neo-, and epi-" indicate different types of isomers.
Suffixes:
"-dine" designates isomerism as quinidine and cinchonidine.
"-ine" indicates, in case of ergot alkaloids, a lower pharmacological activity e.g. ergotaminine is less potent than ergotamine.