PPT. Alkaloids
PPT. Alkaloids
PPT. Alkaloids
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All alkaloids are nitrogenous, but not all the nitrogenous compounds
are alkaloids.
Plants are a rich source of alkaloids but some have been found in
animals e.g. (muscopyridine) of musk deer and fungi e.g. Ergot
alkaloids and almost all alkaloids have been synthesized.
Most but not all possess basic properties due to the presence of an
amino nitrogen but certain are amphoteric e.g. cephaline and
psychotrine or even acidic e.g. colchicines and recinine.
A) Plant sources
` The important alkaloid-bearing families are: Liliaceae, Amarylidaceae,
Asteraceae, Ranunculaceae, Papaveraceae, Leguminosae, Rutaceae,
Loganiaceae, Apocyanaceae, Solanaceae and Rubiaceae.
B) Animal sources
` Recently alkaloids were found in animals and insects e.g, Pyocyanine
from the bacterium Pseudomonas aeruginosa.
` Ergot alkaloids; ergotamine and ergometrine from Ergot fungus.
` Lycopodine from Lycopodium spores, and muscopyridine from the
Musk deer.
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Nomenclature:
Alkaloids terminate with the suffix-ine, their names may be derived from:
Genus name
Species name
Common name
Physiological activity
Discoverer
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2. Pseudo-alkaloids
` These alkaloids derived from non-amino acid precursors.
` Alkaloids of this type are very weak in its basic characters.
` Examples of pseudoalkaloids include such compounds as solanidine, caffeine, theophylline and
theobromine.
` The N atom is inserted into the molecule at a relatively late stage, for example, in case of steroidal
or terpenoid skeletons. Certainly, the N atom can also be donated by an amino acid source across
a transamination reaction, if there is a suitable aldehyde or ketone group
True alkaloids derived from amino acid and they share 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 some are liquids.
True alkaloids may occur in plants (a) free state, (b) as salts and (c) as Noxides.
Examples of true alkaloids include such biologically active alkaloids as cocaine,
quinine, atropine and morphine.
Prefixes:
` "Nor-"
` Designates N-demethylation e.g. nor pseudoephedrine and nor nicotine
` "Apo-"
` Dsigntes dehydration e.g. apomorphine.
` "Iso-, pseudo-, neo- and epi-"
` Indicate different types of isomers.
Suffixes:
` "-dine"
` Refer to isomerism as in the case of the Cinchona alkaloids, quinidine and
cinchonidine are the optical isomers of quinine and cinchonine, respectively.
` "-inine"
` Indicates, in case of ergot alkaloids, a lower pharmacological activity e.g.
ergotaminine is less potent than ergotamine.
Nitrogen in alkaloids:
Number of nitrogen atoms: Alkaloids usually contain one nitrogen atom. Yet,
certain alkaloids may contain more than one up to 5 nitrogen atoms in their
molecule e.g. nicotine contains 2 N atoms and ergotamine 5.
Nitrogen in alkaloids exists in the form of amine as follow:
R1
R1
R1
N R3
R4
Ammonia
Primary
amine
R2
Secondary
amine
R2
R3
Tertiary
amine
R2
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heat
O
CH3 C NH2 + H2O
O
CH3 C OH + CH3 NH2 heat
O
CH3 C NH CH3 + H2O
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Physicochemical Properties:
Physical characters:
1) Condition:
Most alkaloids are crystalline solids. Some are liquids like:
- Volatile e.g. nicotine and coniine, or
- Non-volatile e.g. pilocarpine and hyoscine.
2) Color:
The majority of alkaloids are colorless but some are colored e.g.:
- Colchicine and berberine are yellow. Canadine is orange.
- The salts of sanguinarine are copper-red. Betanine is red.
3) Solubility:
The solubility of alkaloids and their salts is of considerable importance
because:
- They are often administered in solution (injection form).
- The differences in solubility between alkaloids and their salts are used as a
base for their isolation and purification from non-alkaloidal substances.
Due to the great variation in their structure, the solubility of different alkaloids
and salts are variable.
Both alkaloidal bases and their salts are soluble in alcohol.A general rule: the
bases are soluble in organic solvents and insoluble in water. Exceptions:
Bases soluble in waterCaffeine, ephedrine, codeine, colchicine, pilocarpine
and quaternary ammonium bases.Bases insoluble or sparingly soluble in
certain organic solvents: Morphine and psychotrine insoluble ether,
theobromine and theophylline insoluble benzene.
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Alkaloidal salts and the quaternary alkaloid are soluble in H2O, and,
insoluble
or sparingly soluble in organic solvents.
Exceptions:
Salts insoluble in waterQuinine monosulphate.Salts soluble in
organic solvents Lobeline and apoatropine hydrochlorides are soluble
in chloroform.
Generally, salts of weak bases are easily hydrolyzed in solution
without alkalinization and release the bases, which are extracted with
organic solvents e.g. colchicine is soluble as a base or hydrochloride
salt in H2O and CHCl3.
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A) Basicity of alkaloids:
+ H+ClHydrochloric
acid
Amine hydrochloride
. HCl
In plants, alkaloids occur as free bases, salts or N-oxides (NO). When the
salt of an alkaloid is treated with hydroxyl ion, nitrogen gives up a hydrogen ion
and the free amine is liberated.
Quaternary ammonium compounds (R4N+X-), e.g. tubocurarine chloride and
berberine chloride have four chemical groups covalently bonded to nitrogen.
The positive charge of this ion is balanced by some negative ion. The
quaternary ammonium ion, have no proton to give up. Thus; it is not affected by
hydroxyl ion; so quaternary ammonium compounds have chemical properties
quite different from those of the amines.
OCH3
CN
Piperidine
Pyridine
N
CH3
Ricinine
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The influence of different factors such as exposure to light, heat, oxygen, acids and alkalis should be
considered during preservation and manipulation of alkaloids.
In general, alkaloids are less stable in solution than in the dry state.
Effect of heat
Alkaloids are decomposed by heat, except caffeine that sublimes without decomposition.
Effect of heat and light in presence of oxygen:
Most tertiary amine alkaloids are easily transformed to the N oxides when exposed to light and oxygen at
elevated temperature. N-oxides are usually water-soluble, they are characterized by their delayed
release properties, low toxicity and low addictive properties as compared to the parent tertiary
alkaloids.
Effect of acids ,
Hot, dilute acids and concentrated mineral acids may cause:
Dehydration to produce anhydro- or apo-alkaloids, e.g.: dehydration of morphine to produce
apomorphine and that of atropine to yield apoatropine.
O-demethylation of certain alkaloids such as quinine, narcotine and codeine to produce phenolic
alkaloids by treatment with HI e.g. conversion of codeine to morphine.
Hydrolysis of ester alkaloids, such as atropine and reserpine, and glycoalkaloids, such as solanine.
Effect of alkalis
Weak alkalis: liberate most alkaloids from their salts e.g. NH3.They also can form salts with alkaloids
containing a carboxylic group e.g. narceine, when treated with NaHCO3, yields the corresponding sodium
salt.
Strong alkalis: such as aqueous NaOH and KOH form salts with phenolic alkaloids.
Hot alkalis: resulted in hydrolysis of ester alkaloids e.g. atropine, cocaine and physostigmine and
cleavage of lactone ring, if present, to produce the corresponding acid e.g. pilocarpine is transformed to
pilocarpic acid.
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Composition
Remarks
Potassium-mercuric iodide
Iodine in potassium iodide
Saturated solution of picric acid
Potassium bismuth iodide
Potassium cadmium iodide
Color reagents:
Froehd's
Mandalin's
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Marquis'
Erdmann's
Mecke's
Shaer's
Rosenthaler's
Dragendorff's
Vitali-Morin reagent.
Thaleoquine reaction.
Murexide reaction.