The Cardiac The Cardiac GlycosidesGlycosides

Cardio-active GlycosidesCardio-active Glycosides

Group of steroidal glycosides act as Group of steroidal glycosides act as cardiotonic agent. They increase cardiotonic agent. They increase

tone, excitability and contractility of tone, excitability and contractility of cardiac muscles.cardiac muscles.

Structure features:Structure features:

Steroidal nucleus must be Steroidal nucleus must be present.present.

33-OH group involved in -OH group involved in glycosidic linkage.glycosidic linkage.

1414-OH group at C-14.-OH group at C-14. A/B ring junction A/B ring junction ciscis B/C ring junction B/C ring junction transtrans C/D ring junction C/D ring junction ciscis Additional oH groups at C-Additional oH groups at C-

5, C-11 and C-16 may be 5, C-11 and C-16 may be present.present.

The presence of lactone The presence of lactone ring:ring:

R

OH

sug-O

R2

R1

3

5

12

16

17

R3H

H

H

BA

CD

According to the type of lactone According to the type of lactone ring Cardiac Glycosides are ring Cardiac Glycosides are classified into:classified into: Cardinolides:Cardinolides:They are C-23 containing 5-membered They are C-23 containing 5-membered

unsaturated lactone ring unsaturated lactone ring

e.g. e.g. DigitalisDigitalis & & StrophanthusStrophanthus

Bufadienolides:Bufadienolides:They are C-24 containing 6-membered They are C-24 containing 6-membered

unsaturated lactone ring unsaturated lactone ring

e.g. e.g. SquillSquill

OO

17

17

O

O

The Sugar Part:The Sugar Part:

The glycosides usually contain 3 to 4 sugars The glycosides usually contain 3 to 4 sugars attached at C-3 OH.attached at C-3 OH.

Beside Glucose and Rhamnose they usually Beside Glucose and Rhamnose they usually contain deoxysugars.contain deoxysugars.

CHO

CH

CH

CH

CH

CH2OH

OH

OH

HO

OH

Glucose

CHO

CH

CH

CH

CH

CH3

OH

OH

HO

Rhamnose

HO

CHO

CH2CH

CH

CH

CH3

OH

OH

Digitoxose

OH

CHO

CH2CH

CH

CH

CH3

OH

OH

Cymarose

OCH3

The CardinolidesThe Cardinolides1- 1- DigitalisDigitalis Glycosides Glycosides

Known as “foxglove”Known as “foxglove”The most important species includes:The most important species includes:

Digitalis purpureaDigitalis purpurea

Digitalis lanataDigitalis lanata

OO

OH

HO

R2

R1

3

5

12

16

17R1=R2=H DigitoxigeninR1=H, R2=OH GitoxigeninR1=OH, R2=H Digoxigenin

Digitalis contain three major Digitalis contain three major aglycones:aglycones:

Digitoxigenin derived Glycosides: (Glycosylation at 3 OH)

Lanatoside A DX-DX-DX(Ac)-Gl

Purpurea glycoside ADX-DX-DX-Gl

Acetyl-digitoxinDX-DX-DX(Ac)

DigitoxinDX-DX-DX

Gitoxigenin derived Glycosides: (Glycosylation at 3 OH)Lanatoside B

DX-DX-DX(Ac)-GlPurpurea glycoside B

DX-DX-DX-Gl

Acetyl-gitoxinDX-DX-DX(Ac)

GitoxinDX-DX-DX

Digoxigenin derived Glycosides: (Glycosylation at 3 OH)LanatosideC

DX-DX-DX(Ac)-GlDeacetyl lanatoside C (Deslanoside)

DX-DX-DX-Gl

Acetyl-digoxinDX-DX-DX(Ac)

DigoxinDX-DX-DX

-Ac (Alkaline hydr.)

-Ac (Alkaline hydr.)

-Gl (Enzymatic Hydr.)-Gl (Enzymatic Hydr.)

-Ac (Alkaline hydr.)

-Ac (Alkaline hydr.)

-Gl (Enzymatic Hydr.) -Gl (Enzymatic Hydr.)

-Ac (Alkaline hydr.)

-Ac (Alkaline hydr.)

-Gl (Enzymatic Hydr.) -Gl (Enzymatic Hydr.)

2- 2- StrophanthusStrophanthus GlycosidesGlycosides

Obtained from Obtained from Strophanthus Strophanthus kombkombéé

The used part is the seeds.The used part is the seeds.The common aglycone is K-The common aglycone is K-

strophanthidinstrophanthidin

OO

OH

CHO

O

3

5

12

16

17

OH

Cymarose

-Glucose

-Glucose K-Strophanthoside

K-Strophanthin

Cymarin

K-Strophanthidin

BufadienolidesBufadienolides1- 1- SquillSquill Glycosides Glycosides

They have 6-membered lactone ring.They have 6-membered lactone ring.Obtained from Obtained from SquillSquill bulbs. bulbs.Aglycone contains only two hydroxyl Aglycone contains only two hydroxyl

groups at C-3 and C-14.groups at C-3 and C-14.

OH

O

3

5

12

16

17

Rhamnose

-Glucose

-Glucose Glucoscillarin A

Scillarin A

Proscillaridin A

Scillaridin A

O

O

Physical and Chemical Physical and Chemical properties of cardiac glycosides:properties of cardiac glycosides:

Solubility:Solubility:Glycosides are soluble in water and Glycosides are soluble in water and

alcohols.alcohols.Increase number of sugars increase Increase number of sugars increase

water solubility.water solubility.Aglycones soluble in CHClAglycones soluble in CHCl33 and EtOAc. and EtOAc.

Stability:Stability:Acid hydrolysis:Acid hydrolysis:

Split sugars from the aglycone first.Split sugars from the aglycone first.Enzymatic hydrolysis:Enzymatic hydrolysis:

Split sugars stepwise starting from the Split sugars stepwise starting from the terminal sugar.terminal sugar.

Elevated temperature:Elevated temperature:Cause dehydration by removal of C-14 OH Cause dehydration by removal of C-14 OH

group to give inactive anhydro-formgroup to give inactive anhydro-form

OO

OH

Sug-O

OO

Sug-O

High temperature

Anhydro-form

Dehydration of Gitoxin with another OH at C-16 give Dehydration of Gitoxin with another OH at C-16 give a fluorescent compound used as test for Gitoxina fluorescent compound used as test for Gitoxin

OO

OH

HO

OO

HO

Anhydro-form

H2SO4

OH

Medicinal Importance:Medicinal Importance:

They are Cardiotonics used to treat They are Cardiotonics used to treat Congestive heart failure.Congestive heart failure.

They increase force of contraction of cardiac They increase force of contraction of cardiac muscles without increase oxygen muscles without increase oxygen consumption.consumption.

Increase cardiac output.Increase cardiac output. The diastolic phse last longer so decrease The diastolic phse last longer so decrease

heart rate.heart rate. Have diuretic effect due to increase amount Have diuretic effect due to increase amount

of blood passing through the kidney.of blood passing through the kidney.

Chemical Identification:Chemical Identification:

General test for steroids:General test for steroids:Liebermann’s test:Liebermann’s test:

Glycoside in acetic anhydride + Few drops of Glycoside in acetic anhydride + Few drops of conc. Hconc. H22SOSO4 4 Reddish violet GreenReddish violet Green

Test for Deoxysugars:Test for Deoxysugars:Keller-Kiliani’s Test:Keller-Kiliani’s Test:

Glycoside in acetic anhydride containing traces Glycoside in acetic anhydride containing traces of FeClof FeCl33 + conc. H + conc. H22SOSO4 4 on the wall of the tubeon the wall of the tube

Acetic acid layer acquire Bluish-green colour Acetic acid layer acquire Bluish-green colour (Digitalis)(Digitalis)

Acetic acid layer acquire Red colour (Squill)Acetic acid layer acquire Red colour (Squill)

Test for 5-membered lactone ring:Test for 5-membered lactone ring:

Legal’s test: Legal’s test: Cardenolide in pyridine + Na nitroprusside + Cardenolide in pyridine + Na nitroprusside +

NaOHNaOH deep reddeep red colourcolour..

Kedde’s testKedde’s test : : Cardenolide+ 3,5 dinitrobenzoic acid (Kedde’s Cardenolide+ 3,5 dinitrobenzoic acid (Kedde’s

reagent A) + NaOH (Kedde’s reagent B) reagent A) + NaOH (Kedde’s reagent B)

violet colourviolet colour..