Quinoline Alkaloids

Cinchona Alkaloids

Cinchona bark contain many alkaloids the majors are:

1- Quinine and Quinidine.
HO
COOH
2- Cinchonine and Cinchonidine.
Cinchona alkaloids are present
as salts with Quinic and
HO
OH
Cinchotannic acids.
OH

Quinic acid

They are diacidic bases form two types of salts:

1- Neutral salts (Monoacidic) (less water soluble.
2- Acidic salts (Diacidic) water soluble.

 Both Quinine and Quinidine, Cinchonine and Cinchonidine

are Diastereoisomers. Each

stereochemistry at C-8 and C-9.

HO

H3CO

Quinine

in

N
H3CO

differs

HO

pair

N
Quinidine

the

Properties:
Quinine is very slightly soluble in H2O, soluble in
ethanol, chloroform, ether, benzene and other organic
solvents.
Quinine is a diacidic base. It forms 2 types of sulfates:
Quinine monosulfate (neutral and H O insoluble).
2
Quinine bisulfate
(acidic and H2O soluble).

Quinine (l-isomer) gives quinidine (d-isomer) among

other products when warmed with KOH in amyl
alcohol.

Quinine is levorotatory, while quinidine is dextrorotatory.

Separation of the 4 Alkaloids

Powdered Bark
- Alk. CaO + NaOH + H2O
- Reflux with benzene &
- Filtration while hot

Benzene filtrate (Alkaloidal bases)

dilute H2SO4

Acidic aqueous layer (Alkaloidal bisulphates)

pH to 6.5 with Na2CO3

Precipitate (monosulphate)
Quinine
Hot water, Na2CO3

Aqueous solution (Monosulphates)

quinidine,
cinchonine & cinchonidine
NaOH, ether

Quinine
Ether layer
Quinidine & Cinchonidine
-HCl PH=7, Na, K Tart. salt
- filter

Precipitate

Filtrate

Cinchonidine tartrate

Quinidine tartrate

Aqueous layer
Cinchonine

 Tests for identification

1- Fluorescence test:
Solution of the alkaloid in oxygenated acids (e.g H 2SO4, HNO3 or
phosphoric acid) blue fluorescence (+ ve with quinine and quinidine).

2- Thalleoquine test:
Aqueous solution of the alkaloidal salt + Br2 /H2O (few drops till the
appearance of yellow color) + NH4OH emerald green color
(+ ve with quinine and quinidine).

3- Rosequin test (Erythroquinine test):

Aqueous solution of the alkaloidal salt + dil HCl + Br 2 /H2O (few drops till the
appearance of yellow color) + CHCl 3 + pot. Ferrocyanide + NH4OH
red color in the CHCl3 layer (+ ve with quinine and quinidine).

 Uses:

Quinine is used mainly as anti-malarial in a dose

of 2g of quinine sulfate or other salt for 14 days.
Quinidine is used as a cardiac depressant
(anti-arrhythmic), particularly to inhibit auricular
fibrillation in a dose of 0.6-1.6 g of quinidine
sulfate daily.
Cinchonine and cinchonidine are used as antiinflammatory.

Isoquinoline Alkaloids

1- Ipecacuanha Alkaloids
Occurrence:
Ipecac is the dried roots and rhizomes of Cephalis ipecacuanha (Brazilian
ipecacuanha) or Cephalis acuminata (Cartagena or Panama ipecacuanha)
Fam. Rubiaceae.
It contains several alkaloids (2 2.5 %), mainly emetine (50- 70 % of total
alkaloids), with cephaline and psychotrine.

MeO
RO

MeO

OMe
N

OMe
H
N

R = Me Emetine
R=H
Cephaline

HO

OMe
OMe

N
H
N
Psychotrine

 Emetine:
It is non phenolic and levorotatory.
It contains 2 basic nitrogens.

Cephaline:
It is phenolic and levorotatory.
It gives emetine on methylation with (CH3)2 SO4.

Psychotrine:
Occurs as yellow prisms.
It is phenolic and gives cephaline on reduction.
It gives emetine on reduction followed by methylation.

 Isolation of Ipeca
alkaloids:
Powdered
root and rhizome
- Ext. alcohol,Conc., lead acetate.
- Filtration

Filtrate
Alkaloidal bases and salts
- Evap., dil. HCl & Filtration

Residue
Non-alkaloidal sub.

Filtrate (Alkaloidal HCl salts)

- Alk. with NaOH & Ext. with ether

Ether layer
Emetine

Aq.alk. solution(Phenolic alkaloids)

Aqueous layer
(Psychotrine)

- HCl (Alkaloidal salts)

- Alk. NH4OH Ext. ether

Ether layer
(Cephaline)

 Tests for identification of Ipeca alkaloids:

Alkaloidal solution in HCl + Ca hypochlorite orange color.

Emetine and cephaline + Froehd's reagent: dirty green color (the

color with emetine fades by addition of HCl).

Psychotrine + Froehd's reagent: pale green color.

Cephaline and psychotrine + p-nitrodiazobenzene dye soluble in

NaOH purple color.

Psychotrine + conc. H2SO4 + HNO3 cherry red color.

Emetine + Liebermann's reagent black color.

 Uses:

Emetine and cephaeline have antitumour and antiviral

activity, but are too toxic for therapeutic use.
Emetine and psychotrine are mainly used as emetic
drugs.
The crude drug is used as expectorant (due to its saponin
content) .
Emetine HCl and Dehydroemetine (DHE) have
an
antiamoebic effect, and are used for the treatment of
amoebic dysentry and Fasciola.
Ipeca alkaloids are diaphoretic, alone or in combination with
opium (e.g. Dover's powder).

2- Curare Alkaloids

Occurrence:

Curare or South American arrow poison is the dried crude extract, obtained
mainly from Chondrodendron tomentosum (Menispermaceae) and certain
Strychnos species, (Loganiaceae).

Curare contains several alkaloids (4-7%), the most important is d-tubocurarine.

MeO
N

Me

OH H

O
Me
Me

H
N+

OH
OMe

Properties:
d-tubocurarine (4ary alkaloid) is freely soluble in H2O. It is a phenolic
dextrorotatory alkaloid. It is a bis-benzyltetrahydroisoquinoline
alkaloid.

Tests:

Saturated aqueous solution + FeCl3 faint green color green color.

Solution of the alkaloidal HC1 + Na2CO 3 yellow brown precipitate.

Uses:

Tubocurarine chloride is mainly used by i.m. or i.v. routes as

skeletal muscle relaxant.
It is used to control and reduce convulsions of strychnine
poisoning and of tetanus.
It is used as a diagnostic aid in myasthenia gravis.