Alkaloids: alkaloids as pharmaceutical raw materials, opium and its analogue, synthesis of ephedrine, clinical comparison of ephedrine and epinephrine

1. Md. Imran Nur Manik
Lecturer
Department of Pharmacy
Northern University Bangladesh
Natural
products and
secondary
metabolites

2. Alkaloids
Syllabus for Alkaloids: alkaloids as pharmaceutical raw materials, opium and its analogue, syn
thesis of ephedrine, clinical comparison of ephedrine and epinephrine.
Alkaloids may be defined as basic nitrogenous compounds which occur abundantly in
the plant kingdom. They contain one or more nitrogen usually in a heterocyclic ring
and have a marked physiological action on man & animals. The nitrogen may exist as
primary (1° amines), secondary (2° amines) or tertiary (3° amines) amine. These
compounds are basic but the degree of their basicity depends on the structure of the
molecule and presence and location of other functional groups.
Alkaloids as pharmaceutical raw materials:
Alkaloids are natural products. They are the secondary metabolites of plant.
Their structure is diverse varying from simple to very complex structure and their
activity is also highly selective based on the structure. For example-

4. The difference between morphine and codeine is that codeine contains a
methoxy group in place of phenolic hydroxyl group. Morphine is an analgesic and it is
10 times more potent compare to codeine. But codeine is mainly used as anti-tussive
drug. It has mild analgesic.
Again thebaine has structure similar to morphine and codeine (both the
hydroxyl groups are replaced by methoxy groups). But thebaine is neither analgesic
nor anti-tussive and it is mainly used as CNS stimulant.
Thus we can see that the simple molecular modification of principle
compound can give variation of pharmacological action and thus suit the need of
different diseases. So it is easily understandable that nature can give us idea of
designing drug molecules for different indications.

5. Opium alkaloids:Opium:
It is the air dried milky exudates obtained by incising the unriped capsules of poppy
plant (Papaver somniferum Linn. of Papaveraceae family).
The plant poppy is an annual herb with large, showy, solitary flowers having colour of p
ink to purple.
Geographical source:
The plant is indigenous to Asia Minor. The plant poppy is cultivated in many
countries but legal opium production is not permitted in all countries.
Constituents:
More than 30 alkaloids are found in opium. The two principle types of
alkaloids present in opium are –
1.Alkaloids containing partially hydrogenated phenanthrene nucleus:
Examples include morphine, codeine, thebaine etc which act primarily on the CNS and
produce stimulation or depression as well as smooth muscle contraction.
2. Alkaloids having 1-benzyl-isoquinoline structure: Example Narcotine,
Papaverine. They have little CNS action.

6. The most important are the alkaloids
1.Morphine: It is the most important opium alkaloid. It is a phenanthrene derivative
containing an alcoholic and phenolic OH group. Morphine and its salts occur as white
silky crystals, odorless and having a bitter taste. They are classified as narcotic
analgesics and are strong hypnotic and narcotic. Their use tends to induce habit form
ation as well as common side-effects as nausea, vomiting and constipation.
2.Codeine: It is the most widely used opium alkaloid. It is obtained from opium, or by
methylation of morphine or by appropriate reduction and demethylation of thebaine.
If methyl group replaces the hydrogen of phenolic OH in morphine it becomes codeine.
The drug and its salts are narcotics and antitussives. They are used as sedatives
especially in allaying coughs. Its action is similar to that of morphine but is less toxic.
Heroin: Diacetylmorphine or heroine is formed by acetylation of morphine, where the
hydrogen atoms of both the phenolic and alcoholic hydroxyl groups are replaced by
acetyl groups. Its action is similar but more pronounced than that of morphine. Due to its
potency and the danger of habit formation it is not used in medicine.

7. 3. Noscapine
4. Thebaine
5. Papaverine
Also contains alkaloids like: i. Narceine, ii. Protopine, iii. Laudanine, iv. Codamine,
iv. Cryptopine, v. Lanthopine , vi. Meconidine

8. Introduction:
Ephedrine is an Alkaloidal amine having sympathomimetic action. Its action is similar
to adrenaline but there are some differences.
Ephedrine can be extracted from stems of various species of Ephedra or it can be
chemically synthesized.
Chemical synthesis:
1. It is synthesized from benzaldehyde by condensing with nitroethane. The
corresponding compound in then reduced. The L-isomer of the reduced compound is
then methylated to obtain ephedrine.
2. Benzaldehyde is fermented with glucose using yeast. The fermentation of glu
cose leads to pyruvic acid formation with is condensed with benzaldehyde. The conde
nsed compound is hydrogenated in presence of methylamine to yield ephedrine.
Ephedrine

9. Comparison with epinephrine
Criterion Ephedrine Epinephrine
Route of Administration Effective in oral route Must be given in IV route (except when
used as inhaler for asthmatic attack)
Duration of action Prolonged Comparatively shorter
Onset of action
Slower (thus it is more suitable
more chronic asthma and colds)
Comparatively rapid
Potency Comparatively less Greater than ephedrine
Blood-Brain-Barrier
penetration
Greater penetration Penetration is less
CNS activity Greater CNS activity Comparatively less active
Vasoconstriction
Stronger vasoconstriction Comparatively lower vasoconstriction
property.
Tolerance Possible Usually doesn’t occur
Structure
H
C
OH
CH
CH3
H
N
CH3
H
C
OH
C
H2
H
N
CH3
HO
HO
Epinephrine