The Cardiac Glycosides

Cardio-active Glycosides
A Group of steroidal glycosides act as cardiotonic agent. They increase tone, excitability and contractility of cardiac muscles.

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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
-Additional OH groups at C-5, C-11 and C-16 may be present.

R1
12

R
17

C H
14

D OH

16

R2

H B R3

-The presence of lactone ring:

sug-O

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 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
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O O

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

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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
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CHO HO CH HO CH CH OH CH OH CH3
Rhamnose

CHO CH2 CH OH CH OH CH OH CH3

Digitoxose

CHO CH2 CH OCH3 CH OH CH OH CH3

Cymarose
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The Cardinolides
1- Digitalis Glycosides
Digitalis is Known as foxglove The most important species includes: 1) Digitalis purpurea 2) Digitalis lanata

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Digitalis contain three major aglycones:

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

R2

OH

HO

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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)

-Ac (Alkaline hydr.)

Digitoxin DX-DX-DX

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.)

-Gl (Enzymatic Hydr.)

Acetyl-gitoxin DX-DX-DX(Ac)

-Ac (Alkaline hydr.)

Gitoxin DX-DX-DX

Digoxigenin derived Glycosides: (Glycosylation at 3 OH)

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

-Gl (Enzymatic Hydr.)

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Acetyl-digoxin DX-DX-DX(Ac)

-Ac (Alkaline hydr.) PURVI H. KAKRANI, SPSRC, Valasan

Digoxin DX-DX-DX

2- Strophanthus Glycosides
Obtained from Strophanthus komb The used part is the seeds. The common aglycone is K-strophanthidin

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O O

12

17
14

CHO
10

16

OH

OH

K-Strophanthidin

Cymarose

Cymarin

b-Glucose

K-Strophanthin b

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K-Strophanthoside PURVI H. KAKRANI, SPSRC, -Glucose

Valasan

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.

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O O

12

17 16

OH
5

Scillaridin A Rhamnose

Proscillaridin A

b-Glucose

Scillarin A

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Glucoscillarin A PURVI H. KAKRANI, SPSRC, b-Glucose

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Valasan

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.

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 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

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O O

O O

High temperature

OH Sug-O Sug-O
Anhydro-form

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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.

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Chemical Identification:
General test for steroids:
Liebermanns test:
Glycoside in acetic anhydride + Few drops of conc. H2SO4 Reddish violet Green

Test for Deoxysugars:

Keller-Kilianis 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)
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 Test for 5-membered lactone ring:

Legals test:
Cardenolide in pyridine + Na nitroprusside + NaOH deep red colour.

Keddes test :
Cardenolide + 3,5 dinitrobenzoic acid (Keddes reagent A) + NaOH (Keddes reagent B) violet colour.
COOH

O2N

NO2

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