Prof. Dr. Amani S. Awaad

Professor of PharmacognosyPharmacognosy Department,

College of Pharmacy Salman Bin Abdulaziz

University,

Al-Kharj. KSA.

Email: amaniawaad@hotmail.com

Pharmacognosy -2

PHG 322

Glycosides

What are glycosides

*Where it occurs & classes

*Their chemical identifications

and biological activities

Organic natural compounds present in a lot of plants and some animals, these compounds upon hydrolysis give one or more sugars (glycone) and non sugar (aglycone) or called genin.

Definition:

• Glycosides consist of a sugar residue covalently bound to a different structure called the aglycone.

• The sugar moiety can be joined to the aglycone in various ways:

1. Oxygen (O-glycoside)

2. Sulphur (S-glycoside)

3. Nitrogen (N-glycoside)

4. Carbon (Cglycoside)

Glycosides

• -Glycosides and -glycosides are

distinguished by the configuration of the

hemiacetal hydroxyl group.

• The majority of naturally-occurring

glycosides are -glycosides.

• O-Glycosides can easily be cleaved into

sugar and aglycone by hydrolysis with

acids or enzymes.

• Almost all plants that contain glycosides

also contain enzymes that bring about

their hydrolysis (glycosidases).

Glycosides

• Glycosides are usually soluble in water and in polar organic solvents, whereas aglycones are normally insoluble or only slightly soluble in water.

• It is often very difficult to isolate intact glycosides because of their polar character.

• Many important drugs are glycosides and their pharmacological effects are largely determined by the structure of the aglycone.

• Sugars exist in isomeric α and β forms. Both α and β Glycosides are theoretically possible.

• All natural glycosides are of the β Type.

• Some α linkage exists in sucrose, glycogen and starch. Also the glycoside K-strophanthoside (strophanthidin-linke to strophanthotriose (Cymarose + β-glucose + α-glucose).

Glycosides

Classification

1. According to the type of glycosidic

linkage: α- glycoside (α-sugar) and β-

glycosides (β-sugar).

1. According to the chemical group of the aglycone involved into the acetal union:

Glycosides

CH2OH

OH

CH2OH

O-C6H11O5

C6H12O6 +

SugarSalicin

Glycosidic linkage-H2O

a) O-glycoside (OH group) b) S-glycoside (SH group).

CH2 CH CH2C

S C6H11O5

N OSO3K

Glycosidic linkage

Sinigrin

C6H12O6

Sugar

+ CH2 CH CH2C

SH

N OSO3K

N

N

NH2

N

N

H

N

N

NH2

N

N

OOHCH2

H

OH OH

OH

+

OOHCH2

H

OH OH

H

H

Glycosidic linkage

Adenine

C-glycoside (C group). N-glycoside (NH group).

HO OH

CH2OH

O

C6H12O6 +

HO OH

CH2OH

O

C6H11O5

Barbaloin

Glycosidiclinkage

Classification

Glycosides

1. According to the nature of the simple sugar component of the glycoside:

a)Glucosides (the glycone is glucose).

d)Galacosides (the glycone is galacose).c) Mannosides (the glycone is mannose).

b) Arabinosides (the glycone is arabinose).

Classification

Glycosides

4-According to the number of the monosaccharides in the sugar moiety:

a)Monoside (one

monosaccharide) e.g., salicin

b)Biosides (two monosaccharide)

e.g., gentobioside

c)Triosides (three monosaccharide)

e.g., strophanthotriose.

Classification

Glycosides

5- According to the physiological or pharmacological activity ‘therapeutic classification)

a)Laxative

glsycosides.

b) Cardiotonic

glycosides

6-according to the correlation to the parent natural glycoside:

a) primary glycosides e.g., amygdalin, purpurea

glycoside A,

b) Secondary glycosides e.g., prunasin, digitoxin

a.) Alcoholic and phenolic

glycosides (aglycones are

alcohols or phenols)

Classification

Glycosides

7-According to the plant families.

8-According to the chemical nature of the aglycone:

b.)Aldehydic G

(aglycones are

aldehydes).

c.)Cyanogenic G (aglycones

are nitriles or derivatives of

hydrocyanic acid).

d)Anthracene or

anthraquinone G

(aglycones are

anthracene der.).

e) Steroidal G (aglycones are steroidal in nature,

derived from cyclopentanoperhydrophenanthrene)

ClassificationGlycosides

8-According to the chemical nature of the aglycone:

f.) Coumarin G (aglycones are derivative of benzo α-

pyrone).

g.)Chromone glycosides (aglycones are derivatives

of benzo-δ-pyrone)

h) Flavonoidal G (aglycones are 2-phenyl chromone

structure).

i) Sulphur containing or thioglycosides (aglycones

are contain sulphur).

j) Alkaloidal glycosides (aglycone is alkaloidal in

nature) e.g., glucoalkaloids of solanum species.

GlycosidesDeoxy sugers

A- 6-deoxy sugars

1- methylpentoses 2- α-L-rhamnose

C- 2,6-deoxy sugars (called rare sugars)

1- D.digitoxose 2- D.cymarose 3- diginose

B- 2-deoxy sugars

2-deoxy-D-ribose

Characteristic of 2-deoxy sugers:

1. Give positive Schiff’s test for

aldehydes.

2. Positive Keller-Kelliani test.

Glycosides

Physical and chemical properties:

Diversity in structure makes it difficult to find

general physical and chemical properties:

1. A- Most glycosides are water soluble and

soluble in alcohols.

B- Either insoluble or less soluble in non

polar organic solvents.

C- More sugar units in a glycoside lead to

more soluble in polar solvents.

2- Glycosides do not reduce Fehling’s

solution, but when are susceptible to hydrolysis

give reducing sugars (C-glycosides are

exceptions).

Stability and hydrolytic cleavage:

Glycosides

1- Acid hydrolysis:

a- Acetal linkage between the aglycon and

glycone more unstable than that between

two individual sugars within the molecule.

b- all glycosides are hydrolysable by acids

non specific (except C-glycosides).

c- Glycosides containing 2-deoxy sugars are

more unstable towards acid hydrolysis

even at room temperature.

d- C-glycosides are very stable (need

oxidative hydrolysis).

O-Gluc.

HO

OH

HO

Arbutine

hydroquinone

+ glucose

hydrlysis

Stability and hydrolytic cleavage:

Glycosides

2- Alkali hydrolysis:

1- mild alkali 2- strong alkali

3- Enzyme hydrolysis:

1- Enzymatic hydrolysis is specific for each glycoside

there is a specific enzyme that exerts a hydrolytic action

on it.

2- The same enzyme is capable to hydrolyze different

glycosides, but α and β sterio-isomers of the same

glycoside are usually not hydrolysed by the same enzyme.

3- Emulsin is found to hydrolysed most β-glycoside

linkages, those glycoside are attacked by emulsin are

regarded as β-glycosides.

4- Maltase and invertase are α-glycosidases, capable of

hydrolyzing α-glycosides only

Glycosides

Extraction and isolation of glycosides:

1. Water mixed with different proportions

of methanol or ethanol (most suitable

extracting solvent).

2. Non-polar organic solvents are

generally used for de-fating process.

3. Glycosides are not precipitate from

aqueous solutions by lead acetate.

Glycosides

General methods of isolation involve:

1. Destruction of hydrolysing enzymes.

a. Drying for 15-30 min. at 100 C˚.

b. Place plant in boiling water or alcohol 10-20 min.

c. Boiling with acetone.

d. Cold acid pH treatment.

e. Extract at very low temperature.

2. De-fating or purification of the plant material (in case of seeds).

3. Extraction of the glycosidal constituents by alcohol, water or dilute

alcohols. Some times ether saturated with water for dry material.

4. Concentrate the alcoholic extract (to get rid of the organic solvent).

Add water (or hot water)→ filter any precipitate.

5. Purify aqueous extract:

a. Extract non glycosidal impurities by org solvent.

b. Water soluble impurities precipitate by lead acetate.

6. Precipitate excess lead salts.

7. Isolation of the glycosides from the purified aqueous solution, by

crystallization.

Qualitative testing of glycosides:

They do not themselves reduce Fehling’s.but reducing sugars upon hydrolysis.

To test for the presence of glycosides

Estimate reducing sugars before and after hydrolysis. (by acids or enzymes)

Glycosides

Glycosides

Tests depending on the chemical nature of the genin:

1-Steroidal or cardiac glycosides:

Give positive Liebermann’s test (steroidal structure).

2-Anthraquinone glycosides and/or aglycone:

Give positive Borntrager’s test, characteristic reddish

coloration with alkalies.

3-Flavonoidal glycosides and/or aglycones:

Characteristic color with, NH4OH, AlCl3, FeCl3.

4-Cyanogenetic glycosides give upon hydrolysis

hydrocyanic acid can be easily tested by change Na bikrate

paper (yellow) to red color.

5-Sulphur containing glycosides give black precipitate of

silver sulphate upon treatment with AgNO3 solution.

GlycosidesTests depending on the sugar part:

1- Keller Killiani’s test for 2-deoxy sugers:

Specificity of action of the hydrolyzing enzymes is often

applied for the identification of the sugar moieties of

glycosides or even the glycoside as alcohol.

1- Scillarin A [acid hydrolysis] →→→ Scillaridine A + Scillabiose

Scillabiose [Scillabiase] →→→ Rhamnose + glucose.

Glycosides

2- Prunasin [Prunase] →→→ glucose + HCN +

3- Amygdalin [amygdalase] → Prunasin

4- Myrosin enzyme is specific for thio D-

glucosides e.g., Sinigrin and sinalbin.

Glycosides

Special tests based on the chemical structure of the glycoside

Determination of the glycosidic linkages:

1. By the use of α and β glycosidases.

2. By acid hydrolysis of glycosides, immediate

optical activity measurement of the resulting

solution.

Color reactions based on the sugar moiety [2-deoxy

sugars]:

1. Keller Killiani:

glacialacetic acid containing + FeCl3 + H2SO4 →

brown ring free from red (acetic acid a quire blue).

2- Xanthydrol:

xanthydrol in glacial acetic containing 1% HCl +

glycoside [heat]→ red color.

.

Glycosides

1-Cardiac drugs: cardiotonic glycosides e.g., digitalis glycosides,

strophanthus, squill.

2-Laxatives e.g., anthraquinone glycosides of senna, aloes, rhubarb,

cascara, frangula.

3-Counter irritants e.g., thioglycosides and their hydrolytic products

‘allylisothiocyanate’

4-Analgesics e.g., methylsalicylate ‘a hydrolytic product of gaultherin.

5-Anti rheumatic e.g., salicin.

6-Some glycosides are claimed to reduce the capillary fragility e.g.,

flavonoidal glycosides, rutin, hisperidin.

7-Anti-inflamatory: e.g., the glycoside glycyrrhizin has a demulcent,

expectorant and antispasmodic action.

8-More recently as an anticancer agent e.g., amygdalin known in the

U.S. as Laetrile.

Medicinal importance of glycosides:

Glycosides

Cardiac glycosides

1-The genins of all cardiac glycosides are

steroidal in nature, that act as cardiotonic

agents.

2-They are characterized by their highly

specific action cardiac muscle, increasing tone,

excitability and contractility of this muscle,

thus allowing the weakened heart to function

more efficiently

Cardiac glycosides are a group of natural products

characterized by their specific effect on myocardial

contraction and atrioventricular conduction.

In large doses they are toxic and bring about cardiac

arrest in systole, but in lower doses they are important

drugs in the treatment of congestive heart failure.

They have a diuretic activity. Since, the improved

circulation tends to improve renal secretion, which

relieves the edema often associated with heart failure

Glycosides

Cardiac glycosides

Distribution in nature

• Scrophulariaceae

• Digitalis purpurea leaves (foxglove)

• Digitalis lanata leaves – white flowers

• Apocyanaceae

• Strophanthus vine seeds – Africa

• Liliceae

• Urginea bulbs (squill) – Europe, India

• Convallaria leaves (lily of the valley) –also produces a volatile oil perfume

Cardiac glycosides are also found in animalsonly in exceptional cases: Bufadienolides occurin toads (Bufo).

Cardiac glycosides occur in small amounts inthe seeds, leaves, stems, roots or barks of plantsof wide geographical distribution, particularlyof the Fam.

Glycosides

Cardiac glycosidesStructure of glycosides• According to the size of the lactone ring CG divided into

two groups of aglycones;

1-the (C23) cardenolide type [with an ,-unsaturated -

lactone (= butenolide]

2- the (C24) bufadienolide type [di-unsaturated -lactone (=

pentadienolide)].

• All of the aglycones have in common the classic,

tetracyclic, steroidal nucleus.

• The A, B, C and D rings normally have a cis-trans-

cis configuration or less often, a trans-trans-cis

configuration.

• Also common to all the aglycones is the presence

of two hydroxyl groups: one is a 3 secondary

alcohol, the other is a 14 tertiary alcohol.

• All of the aglycones have a constituent at C-17:

an ,-unsaturated lactone.

R

OH

CH3

HO

O

O

X3

X2

X1

2

34

1

56

7

89

10

1112

13

1415

16

17

O

O

OO

1 415

1 6

1 7

2 0

2 1

22

2 3

1 41 5

1 6

1 7

2 0

2 1

22

2 3

2 4

L ac to n e rin g o fC a rd en o lid e

L acto n e rin g o fB u fa d ien o lid e

Glycosides

Cardiac glycosidesStructure of glycosides

All cardio active glycosides are

characterized by the following structural

features:

1. The presence of β-OH at position C-3,

which is always involved in a glycosidic

linkage to a mono, di, tri, OR tetra

saccharide.

2. The presence of unsaturated 5 or 6-

membered lactone ring at position C-17,

also in the β configuration.

3. Additional OH groups may be present at

C-5, C-11 and C-16.

R

OH

CH3

HO

O

O

X3

X2

X1

2

34

1

56

7

89

10

1112

13

1415

16

17

Glycosides

Cardiac glycosides

1- Cardiac glycosides that α-β

unsaturated 5-membered lactose

ring in position C-17 are known as

cardenolides. These are

represented by the digitalis and

straphanthus group.

2- Digitalis glycosides contain

angular methyl group at C-10, while

strophanthus glycoside are

characterized by presence of either

an aldehydic (CHO) or primary

alcoholic (C`H2OH) group at C-10.

Digitalis glycosides R=CH3

Strophanthus glycosides R=CHO OR CH2OH

Classification of of CG

Glycosides

Cardiac glycosides

3- Cardiac agents that have doubly

unsaturated 6-membered lactone ring in

position C-17 are referred to as

Bufadienolides.

4- This group includes the squill glycosides

and the toad venom, Bufotoxin.

Squill glycosides R1=OH, R2=H

Bufotoxin R1 & R2 = ester group

Classification of of CG

Glycosides

Cardiac glycosides

5- The glycone portion at position C-3 of cardiac glycosides may contain four

monosaccharide molecules linked in series. Thus, from a single genin one may

have a monoside, a bioside, a trioside or a tetroside.

6- With the exception of D-glucose and L-rhamnose, all the other sugars that are

found in cardiac glycosides are uncommon deoxy-sugars e.g., Digitoxose,

Cymarose, Thevetose.

Digitoxose Cyamarose Thevetose

Classification of of CG

Glycosides

Cardiac glycosides

Biosynthetic origin

Aglycone of the cardiac

glycosides are derived from

mevalonic acid but the final

molecules arise from a

condensation of a C21 steroid

with a C2 unit (the source of

C-22 and C-23).

Bufadienolides are

condensation products of a

C21 steroid and a C3 unit.

Glycosides

Isolation difficulties:

1. Major difficulty in the isolation of

1ry glycosides from the crude drug..

why?

because 1ry glycosides are converted

into secondary glycosides by

hydrolysable enzymes.

2-Other difficulty is the existence of

several closely related glycosides in

the same drug, which are extremely

difficult to separate and purify.

Cardiac glycosides

GlycosidesI-The cardenolides Cardiac glycosides

A- The Digitalis group

Origin: D. purpurea, D. lanata, D. lutea and D. thapsi

The structures of the common aglycones of the digitalis group are indicated below:

Compounds R1 R2

Digitoxigenin H H

Gitoxigenin H OH

Digoxigenin OH H

DX = Digitoxose,

DX (AC)=Acetyldigitoxose

G = Glucose.

1- Glycosides derived from Digitoxigenin:

a- Lanatoside A = Digitoxigenin---DX---DX----DX(AC)---G.

b- Acetyl-digitoxin =Digitoxigenin---DX---DX----DX---(AC).

c- Digitoxin = Digitoxigenin------DX---DX----DX.

d- Purpurea gly A = Digitoxigenin---DX---DX----DX---G

2- Glycosides derived from Gitoxigenin:

a- Lanatoside B = Gitoxigenin---DX---DX----DX(AC)---G.

b- Acetyl-gitoxin = Gitoxigenin---DX---DX----DX---(AC).

c- Gitoxin = Gitoxigenin------DX---DX----DX.

d- Purpurea gly B = Gitoxigenin---DX---DX----DX---G

3- Glycosides derived from Digoxigenin:

a- Lanatoside C = Digoxigenin---DX---DX----DX(AC)---G.

b- Acetyl-digoxin = Digoxigenin---DX---DX----DX---(AC).

c- Digoxin = Digoxigenin------DX---DX----DX.

d- Deslanoside = Digoxigenin---DX---DX----DX---G

GlycosidesI-The cardenolides Cardiac glycosides

A- The Digitalis group

1. The 1ry glycosides Lanatoside A, Lanatoside B, Lanatoside C are acted by specific enzyme which

split the terminal glucose, give the 2ry glycosides acetyldigitoxin, acetylgitoxin and acetyldigoxin

respectively.

1. The deacetyl-lanatosides A, B and C can be obtained by the alkaline hydrolysis of the

corresponding lanatosides.

1. Digitoxin, gitoxin and digoxin are obtained by the action of alkali on their acetyl-derivatives.

GlycosidesI-The cardenolides Cardiac glycosides

B-The strophanthus group

1- The glycoside K-strophanthoside (a trioside),

K-strophanthin B (bioside) and cymarin (a

monoside) were isolated from different

strophanthus species.

2- The 1ry glycoside K-strophanthoside gives by

hydrolysis one molecule of glucose and the 2ry

glycoside K-strophanthoside B or K-

strophanthin B.

3- The later gives by hydrolysis one molecule of

glucose and the tertiary glycoside cymarin, which

on turn hydrolyze into the genin K-strophanthidin

and the deoxysugar cymarose.

GlycosidesI-The cardenolides Cardiac glycosides

B-The strophanthus group

The seeds of Strophanthus gratus

contains another glycoside named

Ouabain or (G-strophanthin), which

yield on hydrolysis rhamnose and the

aglycone ouabagenin.

Ouabagenin differs from K-

strophanthidin in having 2 additional

(OH) groups at C-1 and C-11 and

having a 1ry alcoholic group at C-10

instead of the aldehydic group.

Ouabain (G-strophanthin)

Glycosides

II-The BufadienolidesCardiac glycosides

This group of cardioactive

agents includes the squill

glycosides (the scillarins) and

the Toad poison (Bufotoxin).

The genins of squill glycosides

differ from those of the

cardenolides in two important

aspects:

1-They have six membered

doubly unsaturated lactone

ring in position C-17.

2- They have at least one

double bond in the steroid

nucleus

Name of glycosides Structure

Glucoscillarin Scillaridin A ---RH—G---G

Scillarin A Scillaridin A ---RH—G

Proscillaridin A Scillaridin A ---RH

The Bufadienolides of Squill

Glycosides

Cardiac glycosidesPhysical and chemical properties

of cardiac glycosides1- Solubility:

The different cardiac glycosides show different solubilities in aqueous

and organic solvents. They are usually soluble in water or aqueous

alcohol and insoluble in the fat solvents with exception of chloroform

and ethylacetate.

* The higher number of sugar units in the molecule, the greater

solubility in water but lower soluble in chloroform.

* Alcohols are good solvents for both the glycosides and the

aglycones. Therefore, they are considered as the solvents of choice

for the extraction of all CG from drugs.

* pet.ether and ether are used for defatting process of drug, they do

not dissolve CG.

Glycosides

Cardiac glycosidesPhysical and chemical properties

of cardiac glycosides1- Stability:

1- Acid hydrolysis cleavage of the glycosides into

aglycones and sugar residues.

2- Specific enzyme usually coexist with CG in plants,

which may split the primary G into G with less sugar

units. Thus, CG deteriorate during drying and storage

unless special precautions are taken.

3- So it is required by many pharmacopoeias that CG

containing drugs must contain not more than specified

moisture content and that these drugs should be stored

in sealed containers over dehydrating agents.

Glycosides

Cardiac glycosidesPhysical and chemical properties

of cardiac glycosides1- Stability:

4- It is recommended to heat stabilize these CG, by

destroying the enzymes at higher temperatures. At

higher temperature, the tertiary OH gp at C-14 may

split off as water, leading to formation of an inactive

anhydro-form of CG.

5- The gitoxin has in addition to tertiary OH at C-14

another secondary OH at C-16. Both OH gps split as

water by the action of H2SO4 with the formation of

two additional double bonds. These with the double

bond of the lactone ring from a

The detection of gitoxin in other digitalis G is based

on the above mentioned reaction

Glycosides

Cardiac glycosides

Chemical identification of cardiac glycosides

• They can be due to the sugars or to the aglycone:

A. Color reactions of the sugars. The only color reactions of the sugars that

are of interest are those specific to 2-deoxyhexoses. e.g. Keller-Kiliani test.

B. Color reactions of the aglycones (steroidal nucleus). These are positive

with any compound containing a steroidal nucleus including cardenolides

or bufadienolide:

1)Antimony trichloride (SbCl3) 2)Liebermann's test (for bufadienolides)

C. Color reactions of the aglycones (lactone ring).

These are characteristic for cardenolides having a five-membered lactone

ring:

1)Kedde’s reagent( 3,5 dinitrobenzoic)

2)Raymond’s reagent( metadinitrobenzene)

3)Baljet’s reagent( picric acid)

4)Legal’s test( alkaline solution of sodium nitroprusside)

Glycosides

Cardiac glycosides

Medicinal importance & Pharmacological properties

2. Diuretics (capillary of the kidneys are

dialated).

• Cardiac glycosides increase the force and

speed of contraction of the heart. In patients

with cardiac insufficiency, this positive

inotropic effect translates into:

1) an increase in cardiac output,

2) an increase in cardiac work capacity without

any increase in oxygen consumption,

3) a decrease in heart rate, and, indirectly,

4) a decrease in arterial resistance.

1. Cardiotonics, rheumatic heart disease,

atherosclerosis.

Glycosides

Cardiac glycosides

Structure-Activity Relationships (SAR)• The cardiac activity is linked to the aglycone.

• The sugar moiety does not participate directly in theactivity, but its presence enhances the activity andmodulates it by modifying the polarity of thecompound.

• Small change in the molecules such as a change ofthe location of the OH gp, modify the cardiacactivity or even eliminate it completely.

• The saturation and/or cleavage of the lactone ring,destroys the cardiac activity

• The presence of a certain number of structuralelements is required for, or at least favorable, to theactivity:

1. The lactone at C-17, and it must be in the configuration.

2. The configuration of the rings. The activity ismaximized when the A, B, C and D rings are in thecis, trans, cis configuration. The C and D rings mustbe cis fused.

3. The substituents. The inversion of the configurationat C-3 diminishes the activity, but 3-deoxycompounds are not completely inactive.

Therefore, the closely related CG, differ

greatly in the rate of absorption, duration of

action and their cumulative effect

Glycosides

Cardiac glycosides

• Squill glycosidesUrginea maritima (L.)

0.1% 2.4% total bufadienolides, 15 glycosides

• White variety: average 0.2%-0.4%

proscillaridin A, scillaren A, glucoscillaren A (aglycone: scillarenin)

scilliphaeoside, scilliglaucoside

• Red variety: < 0.1%

scilliroside and glucoscilliroside (aglycone: scillirosidin); proscillaridin A and scillaren A as in the white variety

Glycosides

Cardiac glycosides

• White variety: average 0.2%-0.4%

proscillaridin A, scillaren A, glucoscillaren A (aglycone: scillarenin)

scilliphaeoside, scilliglaucoside.

• Red variety: < 0.1%

scilliroside and glucoscilliroside (aglycone: scillirosidin); proscillaridin A and scillaren A as in the white variety.

Drugs fro CG1) Squill glycosides

From plant called :Urginea maritima (L.)

0.1% 2.4% total bufadienolides , -15 glycosides

Glycosides

Cardiac glycosidesDrugs fro CG1) Squill glycosides

Pharmacological properties of squill

• White squill:

it is an expectorant, but it also

possesses emetic, cardiotonic

(proscillaridin A), and diuretic

properties.

• Red squill:

it is used as a rat poison (scilliroside),

because rodents lack the vomiting

reflex, which makes red squill

particularly lethal to these animals.

CH3

-D-glucose–O

CH3

O CH3

O

O

O

H

OH

OH

Scilliroside

(3,6)-6-(Acetyloxy)-3-(-D-glucopyranosyloxy)-8,14-dihydroxybufa-4,20,22-trienolide

Glycosides

Cardiac glycosidesDrugs fro CG

2)Digitalis glycosides

Several species of Digitalis yield

pharmacologically active principles. The most

important of these species are Digitalis

purpurea and Digitalis lanata.

1. Digitalis purpurea folium (Red foxglove

leaves)

0.15% 0.4% total cardenolides, 30

glycosides Purpurea glycosides A and B

(60%), digitoxin (12%), gitoxin (10%)

and gitaloxin (10%).

2. Digitalis lanata folium (White foxglove

leaves)

0.5% 1.5% total cardenolides, 60

glycosides Lanatosides A and C (50%),

lanatosides B, D, E as well as digoxin and

digitoxin.

Glycosides

Cardiac glycosidesDrugs fro CG

2)Digitalis glycosides

Digitoxin Digoxin

is a cardiotonic glycoside

obtained from D. purpurea, D.

lanata.

is the most widely used of the

cardiotonic glycosides, and it is

obtained from the leaves of D.

lanata

It is the most lipid-soluble of the

cardiac glycosides used in

therapeutics

It is a highly potent drug and

should be handled with

exceptional care

The major pharmacokinetic

parameters for digitoxin include

complete oral absorption, which

distinguishes it from other cardiac

glycosides.

Digoxin tablets are 60 to 80%

absorbed

Digitoxin may be indicated in

patients with impaired renal

function.

Digoxin is indicated when the

risk of digitalis intoxication is

great, since it is relatively short-

acting and rapidly eliminated

when compared with digitoxin.

Cyanogenic glycosides

Glycosides

• Cyanogenesis is the ability of certain living

organisms, plants in particular, to produce

hydrocyanic acid (HCN, prussic acid).

• Cyanogenesis in plants is a chemical defense

mechanism against organism damaging or feeding

on plant tissues and lead to release of HCN gas,

which is toxic.

• They are distributed in over 2000 plant species

belonging to 110 families.

1- These glycosides are yield hydrocyanic acid as one

of their hydrolytic products.

2- Plant containing these glycosides are toxic.

3- The aglycone part is cyanohydrin of a carbonyl

compound (condensation product of HCN with an

aldehyde or keton).

4- The majority of cyanogenic glycosides are derived

of benzaldehyde cyanohydrin

Cyanogenic glycosidesGlycosides

• These compounds, in presence of enzymes such as

-glucosidase, lose their sugar portion to form a

cyanohydrin which, in the presence of water and

hydroxynitrile lyase, can undergo hydrolysis to

give benzaldehyde and the highly toxic hydrogen

cyanide (HCN).

• The sugar portion of the molecule may be a

monosaccharide or a disaccharide such as

gentiobiose or vicianose. If a disaccharide, enzymes

present in the plant may bring about hydrolysis in

two stages, as in the case of amygdalin.

• They are derivatives of -hydroxynitrile or 2-

hydroxynitrile (cyanohydrins).

• In all cases the first sugar attached to the aglycone is

-D-glucose.

• R1 and R2 are often different residues resulting in

pairs of C-2 epimers.

R1

R2

CN

OSugar

Epimers are diastereomers that differ in

configuration at only one of their

stereogenic centers).

Cyanogenic glycosidesGlycosides

Examples:Amygdalin

1. Amygdalin is the most widely distributed cyanophore

glycoside.

2. It occurs in several Prunus species, and is obtained from

bitter almonds (Prunus amygdalus Var. amara Family

Rosaceae).

3. Amygdalin is considered as gentiobioside of D-

mandelonitrile. Gentiobioside is a reducing disaccharide

consisting of two molecules of β-glucose linked by β-1,6

linkage.

Cyanogenic glycosidesGlycosides

Examples:Amygdalin

1. Amygdalin is the most widely distributed cyanophore

glycoside.

2. It occurs in several Prunus species, and is obtained from

bitter almonds (Prunus amygdalus Var. amara Family

Rosaceae).

3. Amygdalin is considered as gentiobioside of D-

mandelonitrile. Gentiobioside is a reducing disaccharide

consisting of two molecules of β-glucose linked by β-1,6

linkage.

4. Acid hydrolysis of amygdalin split two molecules of

glucose and one molecule of mandelonitrile. The latter

decomposes spontaneously to form benzaldehyde and

HCN.

5. Different enzymes act upon amygdalin in different ways:

Cyanogenic glycosidesGlycosides

Detection of cyanogenic glycosides

The plant material is cut into small fragments

and then a filter paper moistened with sodium

picrate is then suspended in the neck of the

flask, the flask is stoppered and incubated in a

warm place (40˚C) for about 30-60 min.

By this time, the coexisting enzymes act upon

the glycosides with the liberation of HCN

which turns, the sodium picrate paper convert

to brick red color.

Glycosides

Sulphur containing glycosides

Thioglycosides

1- A number of plants of the family Cruciferae

yield glycosides containing sulphur.

2- Hydrolysis of these, yield volatile genins of

thiocyanate structure e.g., mustard oils.

3- The best known compounds Sinigrin and

Sinalbin, two glycosides occurring in black

mustard and white mustard seed respectively.

4- The glycosides and their specific enzymes

are found in different cell in the seeds. They

donot interact until they are brought together by

the distruction of the cell walls.

5- The general structure of thioglycosides is:

Glycosides

Sulphur containing glycosides

Thioglycosides

6- The anion is called the glucosinolate ion, R may

be aliphatic or aromatic. The cation (X) may be a

simple metal ion or a complex organic cation, e.g.,

sinapine ion of sinalbin.

7- Hydrolysis of the glycoside sinalbin gives a

phenolic isothiocyanate (Acrinyl isothiocyanate),

glucose and the acid sulphate of a quaternary

alkaloid, sinapine.

8- Sinigrin gives upon hydrolysis, glucose,

allylisothiocyanate (volatile oil of mustard) and

potassium acid sulphate

9- Black and white mustard seeds are used as

rubefacients and counter irritants. These effects are

attributed to their contents of thioglycosides