Download The Cardiac Glycosides Cardio

The Cardiac Glycosides
Cardio-active Glycosides
A Group of steroidal glycosides act as cardiotonic
agent. They increase tone, excitability and
contractility of cardiac muscles.
Structural features:
-Steroidal nucleus must be
present.
-3b-OH group involved in
glycosidic linkage.
-14b-OH group at C-14.
- A/B ring junction cis –
- B/C ring junction trans-C/D ring junction cis
R1
12
17
C
H
D
14
-Additional OH groups at C-5, C-11 and C-16 may be
present.
-The presence of lactone ring:
R
3
sug-O
A
5
H
B
H
R3
OH
16
R2
• According to the type of lactone ring
Cardiac Glycosides are classified
into:
– Cardinolides:
They are C-23 containing 5-membered
unsaturated lactone ring
e.g. Digitalis & Strophanthus
O
O
17
O
– Bufadienolides:
They are C-24 containing 6-membered
unsaturated lactone ring
e.g. Squill
O
17
The Sugar Part:
• The glycosides usually contain 3 to 4 sugars attached at
C-3 OH.
• Beside Glucose and Rhamnose they usually contain
deoxysugars.
CHO
CH OH
HO CH
CH OH
CH OH
CH2OH
Glucose
CHO
HO CH
HO CH
CH OH
CH OH
CH3
CHO
CH2
CH OH
CH OH
CH OH
CH3
CHO
CH2
CH OCH3
CH OH
Rhamnose
Digitoxose
Cymarose
CH OH
CH3
The Cardinolides
1- Digitalis Glycosides
• Digitalis is Known as “foxglove”
• The most important species includes:
•
1) Digitalis purpurea
•
2) Digitalis lanata
Digitalis contain three major aglycones:
O
O
R1
17
12
16
3
HO
5
OH
R2
R1=R2=H
R1=H, R2=OH
R1=OH, R2=H
Digitoxigenin
Gitoxigenin
Digoxigenin
Digitoxigenin derived Glycosides: (Glycosylation at 3 OH)
Lanatoside A
DX-DX-DX(Ac)-Gl
-Ac (Alkaline hydr.)
Purpurea glycoside A
DX-DX-DX-Gl
-Gl (Enzymatic Hydr.)
-Gl (Enzymatic Hydr.)
Acetyl-digitoxin
DX-DX-DX(Ac)
Digitoxin
DX-DX-DX
-Ac (Alkaline hydr.)
Gitoxigenin derived Glycosides: (Glycosylation at 3 OH)
Lanatoside B
DX-DX-DX(Ac)-Gl
-Ac (Alkaline hydr.)
Purpurea glycoside B
DX-DX-DX-Gl
-Gl (Enzymatic Hydr.)
Acetyl-gitoxin
DX-DX-DX(Ac)
-Gl (Enzymatic Hydr.)
Gitoxin
DX-DX-DX
-Ac (Alkaline hydr.)
Digoxigenin derived Glycosides: (Glycosylation at 3 OH)
LanatosideC
DX-DX-DX(Ac)-Gl
-Ac (Alkaline hydr.)
-Gl (Enzymatic Hydr.)
Acetyl-digoxin
DX-DX-DX(Ac)
-Ac (Alkaline hydr.)
Deacetyl lanatoside C (Deslanoside)
DX-DX-DX-Gl
-Gl (Enzymatic Hydr.)
Digoxin
DX-DX-DX
2- Strophanthus Glycosides
• Obtained from Strophanthus kombé
• The used part is the seeds.
• The common aglycone is K-strophanthidin
O
O
12
CHO
17
14
16
10
3
O
Cymarose
5
OH
OH
K-Strophanthidin
Cymarin
b-Glucose
K-Strophanthin b
-Glucose
K-Strophanthoside
Bufadienolides
1- Squill Glycosides
• They have 6-membered lactone ring.
• Obtained from Squill bulbs.
• Aglycone contains only two hydroxyl
groups at C-3 and C-14.
O
O
17
12
16
OH
3
O
5
Scillaridin A
Rhamnose
b-Glucose
b-Glucose
Proscillaridin A
Scillarin A
Glucoscillarin A
Physical and Chemical properties of
cardiac glycosides:
• Solubility:
– Glycosides are soluble in water and alcohols.
– Increase number of sugars increase water
solubility.
– Aglycones soluble in CHCl3 and EtOAc.
• Stability:
– 1) Acid hydrolysis:
• Split sugars from the aglycone first.
– 2) Enzymatic hydrolysis:
• Split sugars stepwise starting from the terminal
sugar.
– 3) Elevated temperature:
• Cause dehydration by removal of C-14 OH group to
give inactive anhydro-form
O
O
O
O
High temperature
OH
Sug-O
Sug-O
Anhydro-form
Medicinal Importance:
• -They are Cardiotonics used to treat Congestive
heart failure.
• -They increase force of contraction of cardiac
muscles without increasing oxygen consumption.
• -Increase cardiac output.
• The diastolic phase lasts longer, thus decreases
heart rate.
• -Have diuretic effect due to increase amount of blood
passing through the kidney.
Chemical Identification:
General test for steroids:
Liebermann’s test:
Glycoside in acetic anhydride + Few drops of conc.
H2SO4
Reddish violet
Green
Test for Deoxysugars:
Keller-Kiliani’s Test:
Glycoside in gl. acetic containing traces of FeCl3 +
conc. H2SO4 on the wall of the tube
Acetic acid layer acquire Bluish-green colour (Digitalis)
Acetic acid layer acquire Red colour (Squill)
• Test for 5-membered lactone ring:
– Legal’s test:
• Cardenolide in pyridine + Na nitroprusside + NaOH
deep red colour.
– Kedde’s test :
• Cardenolide + 3,5 dinitrobenzoic acid (Kedde’s reagent A) + NaOH
(Kedde’s reagent B)  violet colour.
COOH
O2N
NO2