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
3-OH group involved in - 
.glycosidic linkage R1
R
.14-OH group at C-14-  12
17
A/B ring junction cis -  C
H D R2
-- B/C ring junction trans 16
14
C/D ring junction cis- 
Additional OH groups at C-5, C-11 and C-16 may -  A H OH
3 5
.be present B
The presence of lactone-  sug-O
H
:ring R3
According to the type of lactone ring 
:Cardiac Glycosides are classified into
:Cardinolides – O
O
They are C-23 containing 5-membered
unsaturated lactone ring
e.g. Digitalis & Strophanthus 17

O
:Bufadienolides –
They are C-24 containing 6-membered O
unsaturated lactone ring
e.g. Squill
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 CHO CHO CHO

CH OH HO CH CH2 CH2
HO CH HO CH CH OH CH OCH3
CH OH CH OH CH OH CH OH
CH OH CH OH CH OH CH OH
CH2OH CH3 CH3 CH3
Glucose Rhamnose Digitoxose Cymarose
 The Cardinolides
1- Digitalis Glycosides

”Digitalis is Known as “foxglove 

:The most important species includes 
Digitalis purpurea )1 
Digitalis lanata )2 
 Digitalis contain three major
:aglycones

O
O
R1

12 17
R1=R2=H Digitoxigenin
16 R2 R1=H, R2=OH Gitoxigenin
R1=OH, R2=H Digoxigenin

OH
3 5

HO
Digitoxigenin derived Glycosides: (Glycosylation at 3 OH)
Lanatoside A -Ac (Alkaline hydr.) Purpurea glycoside A
DX-DX-DX(Ac)-Gl DX-DX-DX-Gl
-Gl (Enzymatic Hydr.) -Gl (Enzymatic Hydr.)

Acetyl-digitoxin Digitoxin
DX-DX-DX(Ac) -Ac (Alkaline hydr.) DX-DX-DX

Gitoxigenin derived Glycosides: (Glycosylation at 3 OH)

Lanatoside B -Ac (Alkaline hydr.) Purpurea glycoside B
DX-DX-DX(Ac)-Gl DX-DX-DX-Gl
-Gl (Enzymatic Hydr.) -Gl (Enzymatic Hydr.)

Acetyl-gitoxin Gitoxin
DX-DX-DX(Ac) -Ac (Alkaline hydr.) DX-DX-DX

Digoxigenin derived Glycosides: (Glycosylation at 3 OH)

LanatosideC -Ac (Alkaline hydr.) Deacetyl lanatoside C (Deslanoside)
DX-DX-DX(Ac)-Gl DX-DX-DX-Gl
-Gl (Enzymatic Hydr.) -Gl (Enzymatic Hydr.)

Acetyl-digoxin Digoxin
DX-DX-DX(Ac) -Ac (Alkaline hydr.) DX-DX-DX
Strophanthus Glycosides -2

Obtained from Strophanthus kombé 

.The used part is the seeds 
The common aglycone is K-strophanthidin 
 O
O

12 17

CHO 16
14

10
OH
3 5

O
OH K-Strophanthidin

Cymarose Cymarin

-Glucose K-Strophanthin 

-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
Squill bulb
 O

12 17
16

OH
3
5
O
Scillaridin A

Rhamnose Proscillaridin A

-Glucose Scillarin A

Glucoscillarin A
-Glucose
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 
:Acid hydrolysis )1 –
.Split sugars from the aglycone first 
:Enzymatic hydrolysis )2 –
Split sugars stepwise starting from the terminal 
.sugar
:Elevated temperature )3 –
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
 Dehydration of Gitoxin with another OH at C-16 give
a fluorescent compound used as test for Gitoxin

O O
O O

OH
H2SO4
OH

HO HO
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