Transcript Tropane Alkaloids

Tropane Alkaloids

They are ester alkaloids resulted from the coupling of
organic acids with amino alcohol (Base).
 The parent base is the “Tropane” base.
H
N
1
2
7
6

NH
5
4
3
Tropane Alkaloids are classified into:
1- Solanaceous Tropane Alkaloids.
2- Erythroxylon (Coca) Alkaloids.
1- Solanaceous Tropane Alkaloids
 Occurrence:
Atropa, Datura, Hyoscyamus, Duboisia spp.
 Main Alkaloids
are:
1- Atropine.
2- Hyoscyamine.
3. Hyoscine (Scopolamine).
Atropine & Hypscyamine

Hyoscyamine is the major natural alkaloid with
negative optical rotation (l- form).
 During extraction hyoscyamine racemizes to the
optically inactive dl Atropine.
 Both alkaloids composed of tropine base and tropic
acid.
Tropic Acid
Me
NCH3
O
H
CH 2OH
O
*
Tropine base
N
O
Me
N
CH 2OH
O
O
OH
(-)-Hyoscyamine
O
Atropine
Hyoscine (Scopolamine)

Hyoscine is an ester of l-tropic acid with scopoline
base.
 Hyoscine is a syrupy liquid.
Tropic Acid
O
NCH3
Scopoline base
O
O
OH
Separation of the Alkaloidal mixtures:
Alkaloids in the form of HCl salts
1- Alkalinize by NaHCO3 pH 7.5
2- Extract with Ether
Ether
Hyoscine free base
(pKa = 6.2)
Aqueous layer
Atropine & Hyoscyamine HCl
(pKa = 9.3)
Convert to oxalate salts,
Fractional Crystallization
(Acetone/ Ether)
Atropine Oxalate
Crystals
Hyoscyamine Oxalate
Solution
 Chemical tests:
 Vitali-Morin’s
test:
Solid alkaloid + fuming HNO3 → Evaporate to dryness,
dissolve residue in acetone, add methanolic solution of
KOH → Violet colour.
 P-dimethylaminobenzaldehyde:
Alkaloid + reagent in porcelain dish and heat on boiling water
path → Intense Red Colour → Cherry Red after cooling.

Gerrard’s test:
Alkaloid + 2% HgCl2 in 50% Ethanol →
Red colour Atropine
Red after warming Hyoscyamine
White ppt Hyoscine
 Pharmacological actions and uses:
The three Alkaloids are anticholinergic agents:

Decrease saliva and GIT secretions so used preoperative.
 Decrease motility of smooth muscles so used as
antispasmodics.
 Stimulate respiratory system.
 A mydriatic (causes dilatation of the eye pupil).

An antidote to organophosphorus insecticides.

Hyoscine has more central effect so it is sedative and hypnotic.
Hyoscine is mainly used as antiemetic.

Synthetic and Semisynthetic Derivatives:

Homatropine:
Synthetic drug prepared by passing HCl gas in a mixture of
tropine base and mandelic acid in the presence of water.
Homatropine is less toxic than Atropine. It is hypnotic in
small doses. Homatropine is used as Mydriatic with shorter
effect than Atropine.
NCH3
O
O
OH
 Hyoscine
butyl bromide:
Quaternary Semisynthetic derivative of Hyscine.
It is used as antispasmodic and antiemetic.
-
Br
O
Bu NCH3
+
O
O
OH
2- Erythroxylon (Coca) Alkaloids
 Occurrence:
Coca leaves contain about 2% total alkaloids.
 Main Alkaloids
are:
1- Cocaine.
2- Cinnamylcocaine.
3. a- truxilline.

O
N
H3C
C
OH
OH
Ecogonine
The base for Coca Alakloid is called “Ecogonine”
Cocaine

It is the major Alkaloid in Coca leaves.
 Cocaine is diester Alkaloid.
 Heating at 160 0C in conc. HCl leads to hydrolyses of
cacaine to MeOH, Benzoic acid and Ecogonine base.
COOMe
NCH3
O
Benzoic acid
Ecgonine base
O
Production of Cocaine commercially:



The total Alkaloids are hydrolysed to obtain the free base.
The base is then Methylated with HCl in MeOH.
The Methylated base is then esterified with Benzoly
chloride.
Cinnamylcocaine
COOMe
NCH3
Ecgonine base
O
Cinnamic acid
O
 Uses:
Cocaine was used as local anesthetic.
Cocaine has a CNS stimulant activity so is
one of the widely abused drugs.