2. HETEROCYCLIC ALKALOIDS
QUINOLINE AND ISOQUINOLINE
MOSTAFA MAHMOUD HEGAZY PH.D
Quinoline
N

3. Alkaloids Containing
Quinoline Skeleton
Quinoline
N
◘ These are biosynthetically derived from
tryptophan amino acid. e.g. Cinchona alkaloids.

4. Cinchona alkaloids
 Cinchona is the dried stem and root barks of
Cinchona succirubra (known as Red
Cinchona), C. Ledgeriana., C. calisaya
(known as yellow cinchona), and C.
officinalis (known as pale cinchona) Family
Rubiaceae.

5.  Structural features of Cinchona alkaloids
 1- The basic skeleton of Cinchona
alkaloids is Ruban-9-Ol.
 2- Ruban nucleus is a combined skeleton
formed from a quinoline ring attached to
a quinuclidine ring (a bicyclic ring
contain N) through methylene group.

6.  3- In Rubanol, the methylene group is
oxidized to a secondary alcoholic
group and the carbon atom becomes
Asymmetric (Chiral).
4- Cinchona alkaloids are Di-acidic bases
(due to presence of 2N atoms) they can
form both neutral and acidic salts .

7.  Cinchona alkaloids contains two groups of diastereomers
(levo and dextro)

8. Isolation of Cinchona alkaloids
 The separation is based on the difference in solubility of the different
alkaloids and their salts.
 1- Quinine mono-sulfate is sparingly soluble in H2O.
 2- Cinchonine is almost insoluble in ether.
 3- l- isomers tartrates, quinine and cinchonidine H2O- insoluble, while d-
isomers tartrates, cinchonine and quinidine are H2O- soluble.

11. Properties
 Quinine is a diacidic base. It forms 3 types of sulfates:
 Quinine (l-isomer) gives quinidine (d-isomer) when warmed with KOH
in amyl alcohol.
 Quinine and cinchonidine are levorotatory.
 Quinidine and cinchonine are dextrorotatory.
◘ Quinine monosulfate (neutral and H2O insol.)
◘ Quinine bisulfate (acidic and H2O soluble)
◘ Quinine tetrasulfate (more H2O soluble)

12. 1- For cinchona:
Show blue fluorescence with dil. acids (as dil H2SO4).
2- Quinine and
Quinidine
When few drops of bromine water are added to 2-3 ml of weakly
acidic solution of quinine salt, followed by addition of 0.5-1 ml of
strong ammonia solution  emerald green color (Thalleoquin )
(This reaction is also given by quinidine but not with cinchonine and
cinchonidine).
3- Thalleoquin
test
Tests for identity

13. Uses:
1-Total extract
Bitter stomachic and astringent.
2- For quinine
 Tonic
 Anti-malarial (contra indicated in
pregnancy as it causes abortion).
 Alopecia (stimulate hair growth)

14. Uses:
3- Quinidine is used as a cardiac depressant
(Anti- arrhythmic) to inhibit auricular
fibrillation.
4- Cinchonine and Cinchonidine are used as
anti-rheumatic.

15. ALKALOIDS DERIVED FROM
TYROSINE AMINO ACID
Alkaloids Containing
Isoquinoline Skeleton
Isoquinoline
N
1) Ipecacuahna Alkaloids.
2) Curare Alkaloids.
3) Opium Alkaloids (Papaverine type)

16. Alkaloids of Ipecacuanha
 Ipecacuanha is derived from the dried rhizome and roots
of Cephaelis ipecacuanha or C. acuminata (Rubiaceae).
 The principal alkaloids, e.g. Emetine, Cephaeline and
Psychotrine.
 They possess a skeleton with
1- two tetrahydroisoquinoline ring systems,
2- plus a terpenoid-derive molecule (secologanin).
So Ipeca alkaloids are e.g.
Terpenoid Tetrahydroisoquinoline Alkaloids
Tetrahydroisoquinoline
N
H

17. HO
N
CH3
HO
NH
H H
H
HO
CHO
NH2
HO
H3COOC
O
H
O-glc
H
HO
NH
HO
H3COOC
O
H
O-glc
H
H
Dopamine
Secologanin
Mannich-like
reaction
N-deacetylisoipecoside

19. Pow dered root and rhizome
- Extraction with alcohol,
- Concentration,
- Purification by lead acetate method
- Filtration
Filtrate
Residue
Coloring matter & Non-alkaloidal
substances
- Evaporation to dryness
- Extraction with dil. HCl
- Filtration
Alkaloidal bases and salts
Filtrate
Alkaloidal hydrochlorides
- Alkalinization
with NaOH
- Extraction with ether
Ether layer
Non-phenolic
alkaloids
(Emetine)
- Evaporation
Emetine
Phenolic alkaloids (as phenates)
(Cephaeline & Psychotrine)
- Acidification with HCl
(Alkaloidal salts)
- Alkalinization with NH4OH
- Extraction with ether
Aqueous layer Ether layer
- Extraction with CHCl3 - Evaporation
Psychotrine Cephaline
Aqueous alkaline solution

20. Actions and Uses
1) As an expectorant and emetic.
Emetine has a more expectorant
and less emetic action than
cephaeline.
2) Treatment of amoebic dysentery.
3) The alkaloids have anti-tumor
properties ???

22. Chemical Tests:
 1- Ipecacuanha alkaloids in HCl + Ca-hypochlorite 
Orange color
 2- Froehd’s Reagent (Sulphomolybdic acid):
◘ With Emetine and Cephaline  Dirty green color
(the color with Emetine fades by addition of HCl).
◘ With Psycotrine  Pale green color

23. Chemical Tests:
3) Cephaline and Psychotrine (phenolic alkaloids) +
p-nitrodiazobenzene  dye soluble in NaOH 
Purple color.
4) Psycotrine + Conc. H2SO4 + HNO3  Cherry red
color.

24. Curare Alkaloids (arrow poison)
Curare is the dried crude extract obtained from
Chondrodendron tomentosum (Menispermaceae).
Uses: Curare was used by i.m or i.v. as skeletal
muscle relaxant, especially in surgical operations
such as abdominal surgery, where tense muscles needed
to be relaxed.
Chemical Tests:
1) Saturated aqueous solution + FeCl3  Green color
2) Solution of the alkaloidal HCl + Na2CO3  Yellow
brown color