DPH1 An Introduction to Glycoside KNS & PDV.pdf

AN INTRODUCTION
TO GLYCOSIDES
Prepared By
Dr. Khyati N. Shah
Assistant Professor, Government Pharmacy College, Gandhinagar
&
Dr. Preeti D. Verma
Lecturer, L. M. College of Pharmacy, Ahmedabad

CONTENTS
Definition
General properties
Distribution and Occurrence
Importance
Classification
Chemical tests
General method of isolation and purification
Ms. Khyati N. Shah (GPC) & Dr. Preeti D. Verma (LMCP)
2

DEFINITION
A glycoside is an organic compound, comprising of a
sugar moiety and a non-sugar moiety attached
through a glycosidic linkage.
Non-sugar part is known as aglycone or genin.
Sugar/s part is known as glycone.
So, glycosides upon hydrolysis yields a sugar &
non-sugar portion.
Ms. Khyati N. Shah (GCP) & Dr. Preeti D. Verma (LMCP)
3

For Academic purpose only,
L. M. College of Pharmacy
hydrolysis
Glycosides Sugar moeity + Non-sugar moeity
(glycone) (aglycone or genin)
Both portions attached through
a Glycosidic linkage

For Academic purpose only,
L. M. College of Pharmacy
Example of drugs
Senna, Aloe, Digitalis, Thevetia, Linseed, Mustard,
Liquorice, Dioscorea, Kalmegh, Gentian, Picrrorhiza,
Almond

GENERAL PROPERTIES OF GLYCOSIDES
PHYSICAL PROPERTIES :
State : Amorphous or crystalline solid substances.
Colour : Usually colourless.
Except: Anthraquinone glycosides are orange/red coloured.
Flavone glycosides are yellow coloured.
Optical activity: Optically active & usually laevorotatory.
Hydrolysis: They are easily hydrolysed by water, enzymes
or mineral acids.
6

PHYSICAL PROPERTIES :
Solubility :
Glycosides are soluble in H2O and alcohol, insoluble in
organic solvents.
While aglycones are soluble in organic solvents.
Except: Resin glycosides are insol. In H2O and sol. in organic
solvents.
7

CHEMICAL PROPERTIES :
One –OH group of sugar within the sugar molecule forms
an oxide ring (with aldehyde group)= Hemiacetal
Another –OH group of sugar condenses with –OH group of
aglycone through a glycosidic linkage= Acetals
So chemically they are ‘Acetals’ or ‘Sugar ethers’.
General Chemical Test:
All glycosides give positive Molisch’s test, after hydrolysis.
8

9

DISTRIBUTION
Families Examples
MONOCOT
Liliaceae Aloe, Squill (Scilla)
Dioscoriaceae Dioscorea
DICOT
Leguminosae Senna, Liquorice
Polygonaceae Rhubarb
Scrophulariaceae Digitalis, Picrorrhiza
Apocynaceae Thevetia (Pili Karen), Strophanthus
Gentianaceae Gentian, Chirata
Rosaceae Bitter almond, Wild cherry bark
Rhamnaceae Cascara
10

OCCURRENCE
Part of the
plant
Examples
Bark Arjuna, Cascara, Wild cherry bark, Quillaia
Wood Quassia
Roots and
rhizomes
Senega, Ginseng, Rhubarb, Gentian, Picrorrhiza,
Dioscorea (tuber), Glycyrrhiza (root & stolon),
Aerial
parts/stem
Chirata, Kalmegh
Leaf Senna, Digitalis, Aloe
Fruits Senna pod, Thevetia, Ammi
Seed Mustard, Linseed, Bitter almond, Strophanthus
11

ROLE OF GLYCOSIDES
FOR PLANT ITSELF
• Serve as reservoir of sugar
• By forming glycosides, they increase solubility of aglycone
and thus help (facilitate) transport of such compound.
• Glycosides formation decreases toxicity and reactivity and
therefore allow such compounds to restore or transported
without any harm to the plant.
• They are involved in regulatory and protective processes of
the plant.
12

THERAPEUTIC IMPORTANCE FOR LIVING
ANIMALS
THERAPEUTIC USE EXAMPLES
Laxatives/Purgative
(Anthraquinone glycosides)
Senna, Aloe, Rhubarb, Cascara
Cardiotonics
(Cardiac glycosides)
Digitalis, Arjuna, Thevetia,
Squill, Strophanthus
Bitter tonics &
Hepatoprotectives
(Bitter glycosides)
Kalmegh, Gentian, Picrorrhiza,
Chirata, Quassia
Expectorant Liquorice, Senega, Wild cherry
bark
13
Flavouring agents Vanilla
OTHER COMMERCIAL USES

CLASSIFICATION OF GLYCOSIDES
They can be classified according to
1.Nature/type of sugar
2.No. of sugar
3.Physical or physical property and pharmacological
action
4.Glycosidic linkage
5.Nature or chemical nature of aglycone
14

CLASSIFICATION OF GLYCOSIDES
1. According to chemical nature of sugar.
Disadvantage: If rare sugar is present & if structure
is not known, it will be difficult to name that
glycoside.
Sugar present Glycoside
Glucose Glucoside
Rhamnose Rhamnoside
Galactose Galactoside
Fructose Fructoside
Ribose Riboside
15

2. According to No. of sugar
No. of sugar Glycoside
One Monoside
Two Bioside
Three Trioside
16

3. According to physical or pharmacological action:
According to physical property
According to pharmacological action
Disadvantage: This classification does not include many other compounds
of pharmacognostic interest.
Glycoside Pharmacological action
Cardiac Cardiotonic
Anthraquinone Purgative
Bitter Bitter tonic
Glycoside Physical property
Saponin With water when shaken they gives foam
Bitter They have intensely bitter taste
Cyanogene
tic
Upon hydrolysis they produce HCN
(Hydrocyanic acid) in the form of gas
17

4. According to Glycosidic linkage :
It is one of the modern methods of classification.
According to linkage between Sugar (R) & Aglycone (X),
the glycosides are classified as:
1. O-glycosides:
R is attached to X through O.
X is having free phenolic or alcoholic group.
They can be easily hydrolyzed.
X – OH + HO – R X-O-R + H2O
Eg. Anthraquinone glycosides, Cardiac glycosides,
Cyanogenetic glycosides, Flavone glycosides
18

2. C-glycosides:
R is attached to X through C.
They are not hydrolysed by heating with dilute acids/alkali.
They are hydrolysed by oxidative hydrolysis with FeCl3.
X-CH + HO-R X-C-R + H2O
Eg.
Aloin present in aloe
Cascaroside (Cascara bark)- contains both ‘O’ & ‘C’-glycosides.
. Ms. Khyati N. Shah (GPC) & Dr. Preeti D. Verma (LMCP)
19

3. S-glycosides :
R is attached to X through S.
X-SH + HO-R X-S-R + H2O
Eg. Isothiocyanate glycosides
4 . N-glycosides :
R is attached to X through N.
N-H + HO-R N-R
Eg. Nucleosides (they are essential components of DNA,
RNA, etc.)
20

5. According to chemical nature of aglycone
1. Anthraquinone glycosides
2. Cardiac (Sterol) glycosides
3. Saponin glycosides
4. Bitter glycosides
5. Cyanogenetic glycosides
6. Isothiocyanate glycosides
7. Coumarin glycosides
8. Flavonoid glycosides
21

TYPES OF GLYCOSIDES
1.ANTHRAQUINONE GLYCOSIDES
They have basic ring structure- Anthracene.
Distribution in families – Mainly in dicot families like
Leguminosae, Rhamnaceae, Polygonaceae,
Euphorbiaceae etc…
and in monocot families like Liliaceae.
Anthracene basic ring
22

ANTHRAQUINONE GLYCOSIDES (contd.)
In reduced form, anthraquinones are present as either
anthrone, anthranol or dianthrone.
Reduced forms are more active than the parent
anthraquinones.
Most of them are present as 1,8-dihydroxy derivatives
i.e chrysophanol, aloe-emodin or rhein derivatives.
Ex : Chrysophanol anthrone, Chrysophanol anthranol,
Rhein anthrone etc…
23

O
O O
H OH
O OH
Anthraquinone Oxanthrone
H H H H
Anthranol
Anthrone
O
O
Dianthrone
Reduced forms of
Anthraquinone
24

O
O OH
HO
R
1,8-dihydroxy anthraquinone derivative
R = -CH3 Chrysophanol
R = -CH2OH Aloe-emodin
R = -COOH Rhein
25

Anthrone Anthranol
• Pale yellow
• Alkali insoluble
• Non-fluorescent
• Brownish yellow
• Alkali soluble
• Fluorescent
Oxanthrone
They are intermediate of Anthrone to
Anthraquinone
Dianthrones
They are anthrone diamer, which are therapeutically
more active.
26

USE AND MECHANISM OF ACTION:
➢ Majorly used as purgatives.
➢ They act on large intestine.
A.Q glycosides
Get absorbed from small intestine in blood
It carries them to large intestine
Where they get hydrolysed by intestinal bacteria to
aglycone & sugar
This induces action because of aglycone
Ms. Khyati N. Shah (GCP) & Dr. Preeti D. Verma (LMCP) 27

Two things are observed:
(1)They irritate mucosal membrane.
So increases motility (peristalsis).
So, we get action.
(2) Act on mucosal cells.
Results in opening of Cl- channel.
Stimulate active secretion of Cl-.
Results in net reduction of water & electrolyte absorption.
Results in increase in volume of content.
This increased volume leads to pressure & subsequently
increases peristalsis.
Which gives laxative action.
28

CHEMICAL TESTS :
Simple Borntrager’s Test: Can be applied directly to Aglycone
Aglycone + Alkali
Pink to red colour depending on concentration of the aglycones
Due to phenolate ions.
If crude drug powder is there
Drug pwd + Extract with organic solvent
Separate organic layer + Alkali
Pink colour
29
For ‘O’ glycosides – hydrolysis with acid or alkali
Add alkali or acid, Boil, Cool & Shake with organic solvent
Pink colour

For ‘C’ glycosides – oxidative hydrolysis is needed
Add FeCl3 + HCl , Shake with organic solvent
Pink colour
30
Modified borntrager’s test :

Reduced derivatives : They must be converted to A.Q first.
For Anthrones/Anthranols :
Anthrones/Anthranols + HNO3 A.Q +Alkali
pink colour
Anthranols + Alkali (KOH) + H2O
Strong Yellowish green flourescence
Anthrones gives this test negative.
For Oxanthrones :
Add H2O2 A.Q. +Alkali
Pink colour
For Dianthrones :
Add FeCl3 + HCl/H2SO4 Add Alkali
Pink colour
31

2.STEROL OR CARDIAC GLYCOSIDES
• In these glycosides, the aglycone moiety has steroidal
structure, which is having Cyclopentanoperhydro
phenanthrene nucleus. So they are also known as
‘Sterol glycosides’.
• Distribution in families- Present in monocot family like
Liliaceae and dicot families like Scrophulariaceae,
Apocynaceae, Leguminosae etc…
32

2.STEROL OR CARDIAC GLYCOSIDES (contd.)
CARDIAC GLYCOSIDES
Cardenolides Bufadienolides
C-23 glycosides C-24 glycosides
5-membered lactone ring 6-membered lactone ring
with one double bond with two double bond
Eg- Glycosides of Digitalis, eg- Glycosides of squill
Strophanthus, Thevetia
In both sugar is attached to C-3 position.
33

O
O
OH
O
sugar
O
OH
O
sugar
O
Cardenolides Bufadienolides
34

SUGAR PRESENT IN CARDIAC GLYCOSIDES :
They characteristically contains Deoxy sugars.
1. 2,6-dideoxy sugar. Eg- Digitoxose.
2. 3-OCH3 dvt of 2,6-dideoxy sugars.
E. g. Cymarose, Oleandrose.
3. 6-deoxy hexose. Eg- Rhamnose.
4. 2-OCH3 dvt of 6-deoxy gexose
5. Cyclic sugars
6. Amino & acetylated sugars
35

Test for Cardenolides :
• Kedde’s test :
Alcoholic extract of drug + 2,4-Dinitrobenzoic acid + KOH
Red-Violet colour.
• Legal test :
Drug extract + Pyridine +Na nitroprusside + KOH
Pink to Red colour
• Baljet test :It is the localization test
Drug extract + Na picrate
Yellow to orange colour
36
Chemical tests :

Test for Bufadienolide :
• Tollen’s test
Drug extract + Tollen’s reagent (ammoniacal AgNO3)
Black ppts
Test for Deoxy sugars :
• Keller Killiani’s Test
Drug extract + Glacial HAC + FeCl3(drop)+H2SO4 slowly
from side of the t.t.
Reddish-brown ring at junction of two layer & Upper layer
slowly becomes bluish green.
37

Chemical tests :
Test for sterols:
Liebermann Burchardt’s test :
Glycosides + Acetic anhydride + H2SO4
Red or violet colour, converts to green colour
Both cardenolides and bufadenolides gives this test
positive.
38

THERAPEUTIC USES AND MECHANISM OF ACTION :
➢ Especially digitalis is used in Congestive Cardiac Failure.
➢ Used in CCF, atrial flutter, atrial fibrillation.
Mechanism of action :
• Cardiac glycosides inhibit enzyme Na+ K+ ATPase. So
increases force of systolic contraction.
• Na+ is retained, so Ca+ is accumulated, which causes
increase in contraction of heart muscles. Thus useful in
CCF.
• K+ is lost , so decreases in systolic length, so heart muscles
get more time to relax & arrhythmias are avoided.
Ms. Khyati N. Shah (GCP) &
Dr. Preeti D. Verma (LMCP)
39

3.SAPONIN GLYCOSIDES
PROPERTIES OF SAPONIN GLYCOSIDES :
Saponins are non-crystalline & with water they forms colloidal solutions.
They are soluble in alcohol but insol. in non-polar organic solvents.
Saponin upon hydrolysis gives Sapogenin (aglycone) & Sugar.
They are having high molecular weight.
With water they produces soapy lather (Foam/ Froth). They
decrease surface tension, emulsify oil & water, so useful as emulsifying
agent.
They give ppts with higher alcohol (cholesterol).
They have bitter acrid taste & drugs containing them are usually irritant
to mucous membrane.
They have haemolytic property i.e causes haemolysis of RBC & are
highly toxic if injected in to blood stream. But, if taken by mouth
they are quite harmless.
Many saponins are used as fish poison, as they interfere with
breathing mechanism.
40

Classification based on aglycone
Steroidal saponins Triterpenoidal saponins
E.g.- Diosgenin,
Hecogenin
Sarsasapogenin Tetracyclic Pentacyclic
Eg-Dammarendiol
Lupeol β-amyrin α-amyrin
E.g. Glycyrrhitinic acid E.g. Asiatic acid
Oleanolic acid
41

Importance of saponin glycosides:
Importance of steroidal saponins:
Used commercially for production of
• Corticosteroids like Betamethasone.
• Sex-hormones like Progesterone, Testosterone.
• Oral contraceptive like mestranol.
• Steroidal diuretics like spiranolactone.
• Different steroids like Vitamin-D, Cardiac glycosides.
42

Importance of triterpenoidal saponins:
Drugs Uses
Glycyrrhiza Expectorant, Sweetening agent,
As anti-inflammatory
Senega Expectorant, Stimulant
Ginseng Adaptogen, Tonic, Stimulant.
Quillaia Expectorant
43

Chemical tests :
1.Froth test:
Take 0.1 gm poweder in a test-tube. Shake vigorously with
distilled water for 30 seconds
Leave undisturbed for 20 minutes
If persistent froth, saponin present
2. Haemolytic zone:
0.5 ml blood + 1% gelatin solution prepared in 0.85% NaCl
solution. Mix them on a glass slide
Place a thick transverse section (T.S.) of drug on it
Clear haemolytic zone formed around the section indicates
presence of the saponin in the drug.
44

4. BITTER GLYCOSIDES
Properties of bitter glycosides :
• They are extremely bitter in taste.
• They are soluble in water.
• Characteristically present in the family Gentianaceae.
• Chemically they are not same, but prominent drugs among
them contain glycosides of monoterpene irridoids with pyran
cyclopentane ring.
• They are taken before or during meal, otherwise they
causes digestive disturbances like diarrhoea, vomiting, pain
in stomach.
Examples : Gentian, Picrorrhiza, Chirata, Kalmegh, Quassia.
Importance : Used as bitter tonic, digestive, stomachic.
45

5. CYANOGENETIC GLYCOSIDES
Properties :
• Upon hydrolysis, these glycosides gives HCN (hydrocyanic
acid in gaseous form).
• Chemically they are derivatives of mandelonitrile.
• They hydrolyze in presence of enzyme & give HCN,
benzaldehyde and sugar.
• Characteristically present in family Rosaceae.
Examples: Amygdalin, Prunasin.
Uses :
Bitter almond – Sedative, Demulcent.
Wild cherry bark – Flavouring agent, Expectorant.
46

5. CYANOGENETIC GLYCOSIDES (contd.)
Chemical tests :
Grignard reaction OR Sodium picrate paper test :
Take drug powder in a test tube/flask + moisten with water,
hold sodium picrate paper on the neck of test tube.
Warm the test tube
Yellow color of the paper turns to red
(due to liberation of gaseous HCN & formation of Sodium
isopurpurate)
47

6. ISOTHIOCYANATE GLYCOSIDES
• They are also known as ‘Glucosinolate glycosides’.
• Here aglycone contains isothiocyanate, as it contains sulfur
& nitrogen.
• Characteristically present in family Cruciferae.
• In plants, they are found as thiocyanate which upon
hydrolysis by enzyme myrosinase & H2O gives
isothiocyanate.
Example: Mustard
Uses: Counter irritant (rubefacient), emetic, condiment,
digestive.
Chemical test : Powder + alkali Bright yellow colour.
48

7. COUMARIN GLYCOSIDES :
Properties :
• They are derivative of Benzo-α-pyrone.
• They are volatile and colourless in nature & have aromatic
smell.
• Their alcoholic solutions when made alkaline shows blue
or green fluorescence.
• Coumarins may be present in either free form or glycosidic
form, free form being most common.
Distribution in Families : Umbelliferae, Leguminosae,
Solanaceae, Rubiaceae, etc…
Examples: Psoralea, Ammi visnag, Ammi majus.
49

50
COUMARINS FLAVONOIDS

COUMARIN GLYCOSIDES: (contd.)
COUMARINS
Simple coumarin Condensed coumarin
E.g. Aesculetin,
Scopoletin, Furano coumarin Pyrano coumarin
Umbelliferone. E.g. Psoralen, E.g. Visnadin
Xanthotoxin
Linear furanocoumarin Angular furanocoumarin
51

O O
3
4
5
6
7
8 1
SIMPLE COUMARINS
If, 6= -OH , 7= -OH Aesculetin
6= -OCH3 , 7= -OH Scopoletin
7= -OH Umbelliferone
CONDENSED COUMARINS
O
O
O
O
O
O
Linear furanocoumarins
Angular furanocoumarins
52

Uses :
Drug Uses
Psoralea Psoriasis, Leucoderma, Leprosy
Ammi In leucoderma & vitiligo
Visnaga Coronary dilator, Asthma
Chemical tests :
• Alcoholic extract + Alkali
Blue green fluorescence
• Test with Hydroxylamine HCl
Take ethereal extract+1 drop sated. Alcoholic Hydroxylamine HCl
+ drop of alcoholic KOH
Heat, cool, acidify with 0.5N HCl & Add drop of 1% FeCl3
Violet colour coumarin present
53

8. FLAVONOID GLYCOSIDES
Properties:
• Flavones are Benzo-γ-pyrone derivatives.
• They are mostly polyphenolic colored substances (pigments ,
mostly yellow).
• They are found mainly in dicots, although also present in
monocot & gymnosperm.
• Chemically, they have 15 ‘C’ skeleton, which consist of 2
phenyl rings connected by 3’C’ bridge.
• In chalcone & dihydrochalcone, the bridge is open. But in
other classes 3’C’ bridge is part of heterocyclic ring.
• They occurs as flavone, flavonol, flavonone, Isoflavone &
chalcone.
54

FLAVONOID GLYCOSIDES (contd.)
Uses:
Drugs Uses
Silymarin In liver diseases
Gingko In vascular diseases
Buckwheat Treatment of capillary bleeding
(Rutin- Vit-P)
Citrus fruits In capillary fragility
55

O
O
Chalcone
Dihydrochalcone
Flavanoids/ glycosides
56

O
O
O
O
OH
O
O
Flavone Isoflavone
Flavonol
O
O
OH
Dihydroflavonol
57

O
O
Flavanone
O
O
CH
Aurone
O
O
HO
OH
OH
OH
OH
Quercetin (aglycone of Rutin)
58

Chemical tests :
Shinoda test :
Ethanolic extract + Small piece of Mg ribbon
+3-4 drops of conc. H2SO4
Formation of red colour
Flavanones present
59

Chemical tests :
60
Fluorescence test:
Take 15 ml of methanolic extract in a porcelain dish and evaporate
to dryness on water bath. To the residue, add 0.3 ml 3% w/v boric
acid solution (aqueous) and 1 ml 10% w/v oxalic acid solution
(aqueous). Mix and evaporate the mixture to dryness. Allow the
residue to cool at room temperature and then dissolve it in 10 ml
diethyl ether. Take the ether layer in a clean, dry test tube and
observe fluorescence under U.V. light. A greenish coloured
fluorescence is seen.

Chemical tests :
61
Test with neutral lead acetate solution
Take 1 ml of methanolic extract and add neutral lead acetate
solution (prepared in distilled water). Coloured precipitates are seen.
(Difference between flavonoids and tannin on basis of this
test: Tannins give bulky white ppt with neutral lead acetate
solution, While flavonoids give colored ppt)
Test with alkali: (Because of Chalcones)
Take the powder or 1 ml of methanolic extract and add dilute
ammonia solution. Yellow to reddish colour is seen. Now, add dilute
H2SO4. The yellow-reddish colour disappears.
Palash- slight orange colour
Liquorice- red to orange.

Chemical tests :
62
Test with acid: (Because of leucoanthocyanidins)
Take the powder or 1 ml of methanolic extract and add 1 ml of
80%v/v H2SO4. Following colours are observed in case of different
types of flavonoids:
Orange – Flavone
Pink – Flavonol
Red-purple – Flavanol and Xanthone
Orange to red - Flavonone

63
Practice question
Write the classification of glycosides based upon the chemical nature of its
aglycone (in a tabular form):
Sr.
No
Name Basic moiety/ ring
structure
Example of
drugs
Therape
utic
use
1 Anthraquin
one
glycosides
2
3
4
5
6
7
8

GENERAL METHOD OF ISOLATION AND PURIFICATION
Stas-otto method:
Drug containing glycoside is powdered
Powder is extracted by continuous hot percolation
with alcohol using soxhlet apparatus.
Extract is treated with lead acetate to ppt tannins
Excess lead acetate is pptd as lead sulfide by passing H2S gas
Extract is filtered & concentrated
Purification is done by fractional solubility, fractional crystallization
Or chromatographic techniques such as TLC.
Identification is done by IR, NMR, U.V.-VISIBLE, MASS spectroscopy.
64

References :
•Trease & Evans : Pharmacognosy,15th edition 2002
• C.K.Kokate : Pharmacognosy,19th edition 2002
• Shah & Quadry : Pharmacognosy,12th edition
Revised 2004-2005.
•Tyler & Brady : Pharmacognosy, 8th edition.
• SIM : Medicinal plant glycosides.1968.
65

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