The Cardiac Glycosides

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

Transcript of The Cardiac Glycosides

Page 1: The Cardiac Glycosides

The Cardiac The Cardiac GlycosidesGlycosides

Cardio-active GlycosidesCardio-active Glycosides

A Group of steroidal glycosides act A Group of steroidal glycosides act as cardiotonic agent. They increase as cardiotonic agent. They increase tone, excitability and contractility of tone, excitability and contractility of

cardiac muscles.cardiac muscles.

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Structural featuresStructural features::

--SteroidalSteroidal nucleus must nucleus must be presentbe present..

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

--1414-OH group at C-14-OH group at C-14.. - -A/B ring junction A/B ring junction cis cis

- - B/C ring junction B/C ring junction transtrans--

--C/D ring junction C/D ring junction ciscis--Additional OH groups at C-5, C-11 and C-16 Additional OH groups at C-5, C-11 and C-16

may be presentmay be present..

--The presence of The presence of lactonelactone ringring::

R

OH

sug-O

R2

R1

3 5

12

16

17

R3

H

H

H

BA

CD

14

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According to the type of lactone According to the type of lactone ring Cardiac Glycosides are ring Cardiac Glycosides are classified intoclassified into::

–CardinolidesCardinolides::They are C-23 containing 5-membered They are C-23 containing 5-membered unsaturated lactone ringunsaturated lactone ring

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

–BufadienolidesBufadienolides::They are C-24 containing 6-membered They are C-24 containing 6-membered unsaturated lactone ringunsaturated lactone ring

e.g. e.g. SquillSquill

OO

17

17

O

O

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The Sugar PartThe Sugar Part::The glycosides usually contain 3 to 4 sugars The glycosides usually contain 3 to 4 sugars

attached at C-3 OHattached at C-3 OH..

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

CHO

CH

CH

CH

CH

CH2OH

OH

OH

HO

OH

Glucose

CHO

CH

CH

CH

CH

CH3

OH

OH

HO

Rhamnose

HO

CHO

CH2

CH

CH

CH

CH3

OH

OH

Digitoxose

OH

CHO

CH2

CH

CH

CH

CH3

OH

OH

Cymarose

OCH3

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The CardinolidesThe Cardinolides1- 1- DigitalisDigitalis Glycosides Glycosides

Digitalis is Known as “foxgloveDigitalis is Known as “foxglove””The most important species includesThe most important species includes::

11 ) )Digitalis purpureaDigitalis purpurea 22 ) )Digitalis lanataDigitalis lanata

Page 6: The Cardiac Glycosides

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 aglyconesaglycones::

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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.)

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22 - -StrophanthusStrophanthus GlycosidesGlycosides

Obtained from Obtained from Strophanthus Strophanthus kombkombéé

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

strophanthidinstrophanthidin

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OO

OH

CHO

O

3 5

12

16

17

OH

Cymarose

-Glucose

-Glucose K-Strophanthoside

K-Strophanthin

Cymarin

K-Strophanthidin

10

14

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BufadienolidesBufadienolides1- 1- SquillSquill Glycosides Glycosides

They have 6-membered lactone ringThey 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-14groups at C-3 and C-14..

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Squill bulbSquill bulb

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OH

O

3

5

12

16

17

Rhamnose

-Glucose

-Glucose Glucoscillarin A

Scillarin A

Proscillaridin A

Scillaridin A

O

O

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Physical and Chemical Physical and Chemical properties of cardiac properties of cardiac

glycosidesglycosides::

SolubilitySolubility::–Glycosides are soluble in water and Glycosides are soluble in water and

alcoholsalcohols..–Increase number of sugars increase Increase number of sugars increase

water solubilitywater solubility..

–Aglycones soluble in CHClAglycones soluble in CHCl33 and EtOAc and EtOAc..

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StabilityStability::–11 ) )Acid hydrolysisAcid hydrolysis::

Split sugars from the aglycone firstSplit sugars from the aglycone first..

–22 ) )Enzymatic hydrolysisEnzymatic hydrolysis::Split sugars stepwise starting from the Split sugars stepwise starting from the

terminal sugarterminal sugar..

–33 ) )Elevated temperatureElevated 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

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OO

OH

Sug-O

OO

Sug-O

High temperature

Anhydro-form

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

for Gitoxinfor Gitoxin

OO

OH

HO

OO

HO

Anhydro-form

H2SO4

OH

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Medicinal ImportanceMedicinal Importance::

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

--They increase force of contraction of They increase force of contraction of cardiac muscles without increasing oxygen cardiac muscles without increasing oxygen consumptionconsumption..

--Increase cardiac outputIncrease cardiac output..The diastolic phase lasts longer, thus The diastolic phase lasts longer, thus

decreases heart ratedecreases heart rate..--Have diuretic effect due to increase amount Have diuretic effect due to increase amount

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

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Chemical IdentificationChemical Identification::

General test for steroidsGeneral test for steroids::–Liebermann’s testLiebermann’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 DeoxysugarsTest for Deoxysugars::–Keller-Kiliani’s TestKeller-Kiliani’s Test::

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

Acetic acid layer acquire Acetic acid layer acquire BluishBluish--greengreen colour colour (Digitalis)(Digitalis)

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

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

–Legal’s testLegal’s test:: Cardenolide in pyridine + Na nitroprusside + NaOHCardenolide in pyridine + Na nitroprusside + NaOH

deep deep redred colourcolour..

–Kedde’s testKedde’s test : :Cardenolide + 3,5 dinitrobenzoic acid (Kedde’s reagent A) + Cardenolide + 3,5 dinitrobenzoic acid (Kedde’s reagent A) +

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

violet colourviolet colour.. COOH

NO2O2N