GLYCOSIDES(ANTHRAQUINONES)

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 Glycosides

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

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Glycosides
 More important in medicine than a lot of drugs.
 Occur in higher plant tissues in very small
amounts
 Also fungal and bacterial cells (exuded in
medium) and animals
 Formed by a biochemical reaction that makes a
water insoluble compound more polar than a
water soluble molecule
 Hence can be removed from an organic system
 Man forms them in the liver as part of the process
of detoxification and they are excreted via urine
 Mammalian glycosides are simple compounds
whereas plant glycosides are much larger and
chemically more complex
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 Solubility:

 Glycosides are water soluble compounds

and insoluble in the organic solvents.

 Glycone part: water soluble, insoluble in

the organic solvents.

 Aglycone part: water insoluble, soluble in

the organic solvents.

 Some glycosides soluble in alcohol.

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Separation between glycosides parts:
Hydrolysis
Glycosides +HCLdgillycone +aglycone +HCl
Neutralization by
Filtration
Using aklaGn
il +eA +salt+H2O

(H2O+G) + A ch(Hol 2or Oof +rGm)+

(chloroform+A)
We can separate them by using separating funnel.
The best solvent to extract aglycone is Ethyl acetate because:
A. Immiscible in water.
B. Always presents in the upper layer.

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Note:
Alcohol and acetone are water miscible
compounds , so we can't use them as organic
solvents for aglycone separation.

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 Physico-chemical properties
of glycosides(general)
 Colorless, solid, amorphous, nonvolatile
(flavonoid- yellow, anthraquinone-red
or orange).
 Give positive reaction with Molisch's and
Fehling's solution test (after hydrolysis).
 They are water soluble compounds,
insoluble in organic solvents.
 Most of them have bitter taste.
(except: populin, glycyrrhizin, 7
 Odorless except saponin (glycyrrhizin).
 when a glycosides has a lot of sugars
its solubility in water decrease.
 Glycosides hydrolyzed by using
mineral acids and temperature or by
using enzymes such as:
a. Emolsin Bitter almond seeds.
b. Myrosin or Myrosinase
black mustard seeds.
c. Rhamnase glycosides
containing rhamnose as sugar part.

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The function or the role of
glycosides in the plant
organism
 Converting toxic materials to non or
less toxic.
 Transfer water insoluble substances by
using monosaccharide.
 Source of energy (sugar reservoir).
 Storing harmful products such as phenol.
 Regulation for certain functions(growth).
 Some have beautiful
colours(pollenation process).
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 Some glycosides have antibacterial activity, so
they protect the plants from bacteria and
diseases.

bacteria
kill

hydrolysis
Bitter almond Amygdalin HCN

Eomlsin
enzyme

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Classification
of
glycosides

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Classifications of glycosides according
to their therapeutic effects
 CHF(Congestive Heart Failure)and cardiac
muscles stimulators such as:
a.Digitalis glycosides: digoxin, digitoxin,
gitoxin (Fox glove leaves).
b. Ouabain: Strophanthus gratus seeds.
c. K-strophanthin -Strophanthus kombe seeds.
d.Scillaren A,B which isolated from red and white
Squill bulbs.
e.Convolloside:Convallaria majalis – Lily of the
Valley.

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 Laxative group of glycosides:

a. Sennoside A,B,C,D (Senna leaves and fruits).

b. Cascaroside A,B (Cascara bark).
c. Frangulin and glucofrangulin(Frangula bark).
d. Aloin and barbaloin (Aloe vera and
Aloe barbadensis juice).

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 Local irritant group:
a. Sinigrin (Black mustered seeds-Brassica nigra)
b. Sinalbin (White mustered seeds-Brasica alba)
 Analgesics and antipyretics:
hydrolysis
Salicin Salisylic acid - Willow or Salix
bark.
 Keeping elasticity of blood vessels
like:
Rutin -Rutoside (Bitter orange peels, Lemon peels)
 Anti-inflammatory group:
a. Aloin for 1)acne 2)peptic ulcer
b. Glycyrrhizin

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Classification of glycosides according
to glycone part
 Glucose -glucoside group like in
Sennoside.
 Rhamnose -Rhamnoside like
in frangullin.
 Digitoxose -Digitoxoside like
in digoxin.
 Glucose and Rhammnose
Glucorhamnoside -glucofrangulin.
 Rhamnose and glucose -
Rhamnoglucoside -Rutin. 15
Classification of glycosides on the basis of
the linkage between glycone and aglycone
part
 O-glycosides : In these glycosides the sugar part
is linked with a oxygen atom of aglycone .
 S-glycosides : In these glycosides the sugar
attached to a Sulfur atom of aglycone
,for example
sinigrin.
 N-glycosides : In these glycosides the sugar
linked with Nitrogen atom of (-NH2,-NH-)amino
group of aglycone ,for example nucleosides
DNA,RNA.
 C-glycosides : In these glycosides the sugar
linked (condensed) directly to Carbon atom
of aglycone ,for example aloin.
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Most of glycoside may be named according to the
plant from which they isolated for example:
1. Salicin from salix
2. Cascarosides from cascara
3. Aloin from Aloe vera
4. Sennosides from senna
5. Frangulin from frangula
6. Glycyrrhizin from glycyrrhiza

GENERAL EXTRACTION PROCESS OF GLYCOSIDES;

Always glycosides founded in the plant with the enzymes which hydrolyzed
them.
We must damage these enzymes first to extract these glycoside by the
following steps:
STEP 1. Drying the plants fresh in special oven at 1000c for 30
minutes. STEP 2. Boiling them with organic solvents for 20 minutes
STEP 3. Boiling them with acetone 5 minutes 17
METHYL
GLYCOSIDES
 Methylglucoside is a monosaccharide derived
from glucose. It can be prepared in the laboratory by
the acid-catalyzed reaction of glucose with methanol.

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USES:
chemical intermediate in the production of a
variety of products including
 Emollients.
 Emulsifiers.
 humectants.
 moisturizers.
 thickening agents.
 plasticizers.
 Surfactants.
 varnishes and resins.

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 Preparation of methyl
STEP 1:glycoside
 Methyl glucoside is prepared by the acid-catalyzed
reaction of glucose and methanol .

 In the reaction glucose, methanol and acid

catalyst, anhydrous hydratable CaSO4 are
required .

 In the .preparation of methyl glycoside CaSO4 :glucose

weight ratio of at least 1:1, maintaining the reaction mixture
within the temperature range of about 50 C and 200 C
until formation of methyl glucoside ceases.

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cooling the reaction mixture, neutralizing the acid
catalyst with a base capable of forming a salt of
neutralization which is insoluble in the reaction mixture .

acid catalystC6 H12 O6 +CH3 OH⇋methylglucoside+H2 O (I)

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2. Process according to step 1, wherein the CaSO4 is
incorporated in the reaction mixture in an amount sufficient
to provide a CaSO4:glucose weight ratio from about 1:1 to
about 3:1
3. Process according to step 1, wherein the CaSO4
:glucose weight ratio is from about 1:1 to about 2:1
4. Process according to claim 1, wherein the acid
catalyst is H2 SO4.
5. Process according to step 4, wherein the base is
selected from the group consisting essentially of
Ca(OH)2, Mg(OH)2, Ba(OH)2, Sr(OH)2and mixtures
there of.
6.Process according to step 1, wherein the reaction is carried
out in a closed vessel within the temperature range of about 22
Anthraquinone
Glycosides

Anthraquinone derivatives
Anthraquinone

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 Rhamnus
Aloe purhsianus - Chinese
barbadensis
Cascara Rhubarb

Cassia
senna
Rheum palmatum.
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Introduction to
Anthraquinones
 Historically: Rhubarb, Senna, Aloes and
Cascara were all used as purgative drugs.

 Monocotyledons: Only Liliaceae.

Most commonly C-glycoside: barbaloin.

 Dicotyledons: Rubiaceae, Leguminosae,

Polygonaceae, Rhamnaceae, Ericaceae,
Euphorbiaceae, Lythraceae, Saxifragaceae,
Scrophulariaceae and Verbenacacea. Also in
certain fungi and lichen.
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 Reduced derivatives of anthraquinones
 Oxanthrones, anthranols and anthrones

 Compounds formed by the union of 2 anthrone

molecules
 Dianthrones

 Aglycones:
 Chrysophanol/Chrysophanic acid 
Rhubarb and Senna.
 Rhein  Rhubarb and Senna
 Aloe-emodin  Rhubarb and Senna
 Emodin  Rhubarb and Cascara
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Anthraquinones – Chemical
Properties
 Anthraquinone derivatives: orange-red
compounds
 Soluble in hot water/dilute alcohol.

 Identified via Borntrager’s test

 Powdered drug – macerated with ether
 Filter

 Add ammonia/caustic
 Shake  pink, red or violet colour –
positive for anthraquinone derivatives
 If the Anthraquinones are reduced (within the
herb) or
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Anthraquinone
Structure

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Anthranonls and
Anthrones
 Reduced anthraquinone derivatives.
 Occur either freely (aglycones) or as glycosides.
 Isomers.

 Anthrone: Parent structure (pale yellow,

non- soluble in alkali, non-fluorescent)

 Anthronol: brown-yellow, soluble in alkali,

strongly fluorescent
 Anthronol derivatives (e.g. in Aloe – have similar
properties – fluorescence used for identification)
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Oxanthrones

 Found in Cascara bark oxanthrone

 Intermediate products (between anthraquinones

and anthranols)
 When oxidised oxanthrones it form
anthraquinones
 Oxanthrones are detected by Modified
Borntrager’s Test
(oxanthrones oxidised using hydrogen
peroxide)
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Dianthrones
 Derived from 2 anthrone
molecules
 2 molecules may/not be
identical
 Dianthrones are form easily
due to mild oxidation of
anthrones
 It form important
aglycones
 Cassia
 Rheum
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Structure-Activity Relationship

General structure of glycoside

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 Glycosylation is essential for activity.

 Hydroxylation at C-1 and C-8 is essential for activity.

 Oxidation level at C-9 and C-10 is important:

 Highest level of oxidation (anthraquinones) have the
lowest activity.
 Oxanthrones are less active than anthrones.
 Complete reduction of C-9 and C-10 eliminates the
activity.

 Substitution at C-3 have great impact on activity:

CH2OH > CH3 > COOH
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Mechanism of
Action:
 The glycosides are absorbed from the small
intestine and re-excreted in the large intestine
where they increase the motility so produce
laxation.

 Aglycones produce griping effect so it is

recommended to prescripe antispasmodic with
them.

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Mechanism of
action
 Molecules have to possess certain features for
activity:
1 glycosides
2 carbonyl keto function on centre ring
3 1,-8- positions have to have –OH
 Potency:
 anthrone > anthraquinone> dianthrone

 Aglycones not therapeutically active in animals ,

lipid soluble absorbed in stomach and never reach
colon to produce a local effect.

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 Highly active phenolic group irritant to mucosa

 Glycosides very water soluble – reach large intestine

where they are hydrolysed by E.coli enzymes and
become lipid soluble and absorbed into circulation.

 5-8 hours to act

 take night before

 in low doses – drug metabolised by liver and recirculated

via bile to give more effect

 people especially elderly can become reliant on them

needing higher dose to produce an effect

 carcinogenic to melanosis coli

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Senna -
Leguminosae
 Definition: Consists
of the dried leaflets of
Cassia senna
(Alexandrian senna), or
Cassia angustifolia
(Tinnevelly senna).

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 Senna -
 Constituents
Senna consist four types of glycosides:
Sennoside A
Sennoside B
Sennoside C
Sennoside
D
In their active costituents are
sennoside A, sennosides B
 Upon hydrolysis of sennosides it gives two
molecules
glucose+aglycones: Sennidin A and
Sennidin B.

 Sennoside C & Sennoside D

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 Chemical
Borntrager’s and
testModified Borntrager’s test:
 For Aglycones:
 Extract plant material with organic solvent.
 Shake with NH4OH OR KOH.

 For O-Glycosides:
 Boil plant material with dil. HCl for 10 min, filter and shake with organic solvent
(Ether or Benzene).
 Separate the organic solvent.
 Shake with NH4OH OR KOH.

 For C-Glycosides:
 Boil plant material with dil. HCl/FeCl3, filter and shake with organic solvent
(Ether or Benzene).
 Separate the organic solvent.
 Shake with NH4OH OR KOH.

 Positive result indicated by Rose Red colour in the aqueous

alkaline layer.
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