Alkaloids of
Phenylalkylamine
Alkaloid-like amines. Have no nitrogen as part
of the heterocyclic ring.
Distribution :
This group of alkaloids occurs in many plants
and can be classified into the followings:
a. Beznylamine type (e.g. the capsaicinoids)
b. Phenylethylamine Type (e.g. mescaline)
c. 2-aminophenylpropane type
(e.g. ephedrine, cathinone)
N
R
R
R
Benzylamine type
N
N
R
R
R
Phenylethylamine-type 2-Aminophenylpropane-type
Biosynthetic Source:
It derived from Phenylalanine
amino acid
Ephedra alkaloids
 They are present in the arial parts of several Ephedra species, especially
Ephedra sinica (Family Ephedraceae).
•
The plant contains alkaloids, which are phenylethylamine derivatives
(derived from l-phenyl alanine), among these (-) ephedrine (l- ephedrine)
(1-3%) its stereoisomer (+) pseudoephedrine (d-ephedrine).
Psudoephedrine
Ephedra sinica
d,l-Ephedrine
Epinephrine (Adrenaline)
Ephedra alkaloids
1- Ephedrine:
A-Properties:
Ephedrine occurs as solid, steam volatile (i.e. sublimable) alkaloid.
It is a strong base (why??), soluble in water.
It does not give a precipitate with Mayer's reagent in diluted solution (Gives only
with conc solutions).
B- Isolation from the plant material:
Steam distillation (free base volatile with steam), or by applying any of the usual
procedures for extraction of alkaloids.
Shaking with dilute HCl, which extracts both
ephedrine and pseudo-ephedrine as their hydrochloride salts followed by
separation of the mixture.
Separation of ephedrine from pseudo-ephedrine:
-Ephedrine is more soluble in water than psudo-ephedrine.
-Ephedrine oxalate is less soluble in water than psudo-ephedrine oxalate.
Ephedra alkaloids
C-Tests for identification:
Color test:
Chen's test (Copper sulphate test):
To a solution of ephedrine in water add two drops of 5% CuSO4, and 0.5
ml 20% NaOH, a violet color is produced, on shaking with 1 ml ether or
benzene, the organic layer acquires a purple color and the aqueous layer
a blue color.
Ephedra alkaloids
D-Pharmacological action and uses:
Ephedrine is an indirectly acting sympathomimetic amine similar to
noradrenaline.
It is effective orally and has a longer duration of action than
noradrenaline (biological catechol amines are rapidly deactivated
my COMT enzyme, while ephedra alkaloids are not).
COMT
Adrenaline
In active
metabolite
Ephedra alkaloids
Oral administration of ephedrine causes:
-Peripheral vasoconstriction, (α-agonist effect)
-Bronchodilator effect (β-agonist effect)
-CNS effects (antidepressant and anorexic effect).
Psudo-ephedrine can act only as an α-agonist, so it can be use as a peripheral
vasoconstrictor (e.g. nasal decongestant), and has very minor CNS effect, so psudoephedrine is more safer than ephedrine.
Both ephedrine and psudo-ephedrine should be used with caution in
Hypertensive
patients due to their vasoconstrictive effect.
Β-agonist effect
-Bronchodilator
-CNS stimulant
effects.
Ephedrine
Psudoephedrine
α-agonist effect
Prepheral vasoconstrictor
(Nasal decongestant)
Ephedra alkaloids
Due to its CNS stimulant effects, and being used as a starting material for
the
simple
synthesis
of
the
more
potent
CNS
stimulant
drug
(Methamphetamine), ephedrine is regulated as a narcotic drug in many
countries worldwide.
Ephedrine has been inspired the development of several synthetic drugs
For example:
-The anorexic drug sibutramine (Meredia®) that has been used for weight
control.
-Xylometazoline (Otrivin®), that has been used as a topical nasal
decongestant.
Sibutramine
Xylometazoline
Alkaloids of the pyridine group
Alkaloids belonging to the pyridine group, are subclassified according to the
building nuclei into compounds containing:
1.Pyridine nucleus only e.g. Trigonelline from fenugreek.
2.Pyridine nucleus with another nitrogenous ring e.g. tobacco alkaloids.
3.Piperidine nucleus e.g. Pepper, Conium, Lobelia and Pomegranate alkaloids.
4.Pyridone nucleus e.g. Ricinine from castor seeds.
Trigonilline
Nicotine
Coniine
Ricinine
1-Fenugreek alkaloids (Pyridine alkaloids)
Trigonelline (aka Caffearine) occurs in many seeds as Foenugreek (Trigonella
foenum-graecum) and coffee (Coffea arabica).
A-Properties:
It is , very soluble in water, derived from nicotinic acid (can be semisynthesised from nicotinic acid by methylation), which is biosynthesized from
L-tryptophan.
It can be easily hydrolysed by HCl, to give methyl chloride and nicotinic acid.
B-Uses:
Trigonelline is used as a hypoglycemic agent in diabetic patients, as it slows
down the metabolism of nicotinic acid, which increase the glucose uptake form
blood and its subsequent oxidation.
CH3I, (Methylation)
HCl (250°C, Hydrolysis)
Trigonelline
Trigonelline
Nicotinic acid
2-Tobacco alkaloids (Pyridine).
Tobacco is the cured and dried leaves of Nicotiana tabacum Fam.
Solanacea
A-Properties:
Nicotine possesses two basic nitrogen atoms. It can unite with two
molecules of monobasic acids. The weaker basic nitrogen is that in
the pyridine ring (Why?).
Nicotine decomposes upon exposure to UV light and air to give
nicotine oxide ;nicotinic acid and methylamine.
Anabasine
Nicotelline
Nicotine
Nor-nicotine
2-Tobacco alkaloids (Pyridine).
D-Pharmacological action:
Nicotine has a little use in medicine, due to its high toxicity (LD50 = 3
mg/kg, oral), and being highly addictive compound.
In small doses, it can act as a respiratory stimulant, and can help in
treating nicotine dependence (e.g. nicotine patches, lozenges and sprays).
Nicotine can also be used as insecticide in the form of tobacco extract.
Nicotine can be used commercially to produce one of a
vitamin
B- complex named nicotinic acid or Niacin (Vitamin B3) used to prevent
Pellagra.
3-Pepper alkaloids (Piperidine alkaloids)
In the fruits of pepper species e.g .Piper nigrum Fam.
Piperaceae.
A-Properties:
Piperine is a solid, weak basic alkaloid. It does not form
stable salts .
It is decomposed easily with alcoholic potash to yield
piperidine and piperic acid.
B- Uses:
Piperine used as condiment . It also used in certain
tonic and rubifacient preparations.
NaOH, hydrolysis
4-Conium alkaloids (Piperidine alkaloids)
In hemlock fruits , Conium maculatum ,Fam. Umbelliferae.
The juice from hemlock plant was a primary constituent used by ancient
Greeks in executing criminals.
An extract of hemlock was used to cause the death of Socrates around 400
BC The major alkaloid of hemlock is coniine.
It contains a group of toxic alkaloids of which, coniine and ɣ-coniceine are
the main examples.
A-Properties:
Both coniine and ɣ-coniceine are liquid, volatile with characteristic mice-like
odor.
D-Pharmacological action and uses:
Coniine (LD50 =7 mg/kg, by oral) has a neuromuscular blocking effect. On
autonomic ganglia (nicotinic receptor blocker), it produces initial
stimulation and subsequent blockage.
Coniine has been used as a local analgesic , mostly in external
preparations, due to its high toxicity. It is used as an ointment for
treatment of hemorrhoids and anal fissures.
ɣ-coniceine
Coniine
5-Lobelia alkaloids (Piperidine alkaloids)
Lobelia herb or Indian tobacco is the dried
leaves and flowering tops of Lobelia inflata ,
Fam. Lobeliaceae (Campanulaceae).
B-Pharmacological action and uses:
Lobeline produces similar, pharmacological effects as
nicotine, however it is not addictive so, lobeline sulfate
incorporated in tablets or lozenges, to aid in breaking the
tobacco habit (smoke cessation).
It is used as antiasthma, respiratory stimulant
(bronchodilator) in low dose and as expectorant due to its
irritant effect on the stomach.
Lobelia inflata
Lobelanine
l-Lobeline
Lobelanidine
6-Pomegranate alkaloids (Piperidine alkaloids)
The fruit rind, as well as, the root and stem barks of pomegranate, Punica
granatum, Fam. Punicaceae, contain several alkaloids.
A-Properties and uses:
Usually isolated as a pelletierine tannate. The tannate form of pelletierine is
used because it is less soluble in the stomach, so it is less able to be absorbed
(local action).
Pelletierine
Isopelletierine