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.
• 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.
Separation between glycosides parts:
Glycosides Hydrolysis
glycone +aglycone +HCL
+HCLdil
Neutralization by
Filtration
G
+
A
+salt+H
2
O
Using alkaline
chloroform
(H2O+G)+A
(H2O+G)+(chloroform+A)
We can separate them by using separatory
funnel
The best solvent to extract aglycone is Ethyl
acetate because:
A- immiscible in water.
B- always presents in the upper layer.
Note:
Alcohol and acetone are water miscible
compounds,so we can't use them as
organic solvents for aglycone separation.
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, stevioside).
Cont...
• 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.
Biosynthesis of glycosides
(O-glycosides)
• UTP(Uridine Triphoshate) +sugar-1-phoshate
UDP-sugar + ppi(Pyrophosphate inorganic).
Glycosyl transferase
• UDP-sugar +acceptor (aglycone)
Enzyme
Glycosyl transferase
Acceptor-sugar +UDP
Enzyme
Uridylyl transferase
Enzyme
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).
Cont…
• Some glycosides have antibacterial
activity, so they protect the plants from
bacteria and diseases.
bacteria
kill
Bitter almond
Amygdalin
Eomlsin
enzyme
hydrolysis
HCN
Classification of glycosides
Classifications of glycosides
according to their therapeutic effects
• CHF 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.
Cont…
• 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).
Cont…
• Local irritant group:
a-Sinigrin(Black mustered seeds_Brassica nigra)
b-Sinalbin(White mustered seeds_Brasica alba)
• Analgesics and antipyretics:
Salicin hydrolysis 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
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.
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 alcoholic or phenolic hydroxyl or
carboxyl group.
• S-glycosides : in these glycosides the sugar
attached to a Sulfur atom of aglycone such as in
sinigrin.
• N-glycosides : in these glycosides the sugar
linked with Nitrogen atom of (-NH2,-NH-)amino
group of aglycone like in nucleosides DNA,RNA
• C-glycosides : in these glycosides the sugar
linked (condensed) directly to Carbon atom of
aglycone like in aloin.
N.B C-glycosides are not hydrolyzed by acids or alkalis or by
enzymes mainly .
Classification of glycosides according to a glycone part :
1- if a glycone part alcohol -this group called alcoholic group like Salicin
2- if a glycone part aldehyde- this group called aldehydic gr. like
glucovanillin.
3- if phenol called phenolic group like arbutin .
4-if cyanone called cyanogenic or cyanophoric or cyanoside like
amygdalin.
5-if thio called glycosides or isothiocyanate glycoside like sinigrin or
sinalbin (-S=C=N-) (SCN)
6-anthracene -------> anthraquinone glycoside –sennoside-.
7-steroid ------ steroidal glycoside (cardiac) Digoxin
8-flavone ,flavonol, flavanone –flavonoid glycoside
9-triterpenoid –saponin glycoside –glycyrrhizin ,melanthin (nigella
seeds) or ginsenoside .
Most of glycoside may be named according to the plant from which they isolated
for example:
1-salicin –salix2-cascaroside _cascara
3-aloin- Aloe vera
4- sennoside – senna5-frangulin – frangula
6- glycyrrhizin – glycyrrhiza
And others.
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:
1-drying the plants fresh in special oven at 100 c for 30 minutes.
2-boiling them with organic solvents for 20 minutes
3- boiling them with acetone 5 minutes
N.B.
If present in this plant tannins or resins we add lead acetate to precipitate them.
Classification of glycosides according to a glycone part.
1- phenolic group of glycosides:Such as arbutin which isolated from bearberry leaves
Uses: UTI as antiseptic and antibacterial & mild diuretic
Drugs :
-Esoterica :cream :age spots
-hydroquinone solution : wet hands
2- saponin group of glycoside
a. Important group of glycosides which widely distributed specially in the
higher plants parts
b. Most of them are neutral compounds, soluble in water insoluble in the
organic solvents.
d. Irritant compounds for mucous membranes
e. They form with hydrolysis glycone part which usually β-D-glucose or it’s
acids (glucuronic acid) + Sapogenin
f. Their aqueous solutions from froths (foam) on shakin and form
emulsions on shaking and heating with oils and fats
g. They destroy RBC (corpuscles) specially for fish and cold blooded animals
m. Sapogenin (Triterpenoid) divided to :
1- steroidal Sapogenin 2- pent acyclic Sapogenin
Examples:- licorice roots contain saponin glycoside which called Glycyrrhizin
Glycyrrhizin
hydrolysis glycyrrhetic acid + Z.M. glucyr acid
Sweet taste : solution in H2O
bitter taste insoluble in H2O
expectorant
anti-inflammatory
Ginseng roots
Panax roots
Panax quinquefolius ,panax ginseng -contains saponin glycoside –
ginsenoside ( panaxoside)
Triterpenoid + steroidal nucleus
Ginseng root uses : 1- stimulant
4-adaptogenic agent .
Drugs :
1- geriatric pharmaton
2- gerimax
3- polyvit
2- Tonic 3- anti-stress
Anthraquinone group of glycosides
1. They are anthracene derivatives (anthracene = is the main
nucleus for anthraquinone compounds.
2. In the plant they biosynthesized from acetyl-CoA and
malonyl-CoA.
3. They have cathartic property (laxatives and purgative but some
of them have anti-inflammatory activity.
4. With hydrolysis they give aglycone part which is di,tri or tetra
hydroxy anthracene derivatives.
5. They hydrolyzed only by acids or by enzymes, but not
hydrolyzed by alkalines.
6.They have orange or red color (most of them)
7.Soluble in water, insoluble in the organic solvents.
8. They have bitter taste and slightly characteristic odor.
9. Anthraquinone may be free state compounds (free from sugar)
or anthraquinone glycoside.
Relationship between anthracene derivatives
According to linkage between glycone part and aglycone part
anthraquinone glycoside may classified to :
1.C-glycoside … very stable to hydrolysis.
2.O-glycoside … 3-o and c- glycoside.
Alcoholic group of glycosides
Such as: Salicin which obtained from Salix bark, Willow bark.
Salicin hydrolyzed by:
1.Enzyme emolsin
2.Acid like HCl,HNO3
3.Alkaline solutions like NaOH
The effect of salicylic acid :
1.
2.
3.
4.
5.
6.
Analgesic.
Anti-pyretic.
Anti-coagulant (anticlotting agent).
Anti- inflammatory activity (Rheumatism)
Wart and corn remover
Prevents colon cancer
Aldehydic group of glycoside
Such as :
Glucovanillin which obtained from :
Vanilla beans (fruits)
** Vanillin : volatile oil which used as flavoring agent
** vanillin : 1.phenolic group volatile oils
2.aldehyde group of volatile oils
Isothiocyanate group of glycoside
( sulfur glycoside or thio glycoside )
1. Group of glycosides which contains sulfur (Sglycoside)
2. Present in many cruciferous plants, on hydrolysis.
3. They produce isothiocynate (SCN) aglycone
Such as : 1.sinigrin which founded in Black Mustard
seeds
2.sinalbin which founded Brassica alba --White Mustard seeds.
These plants contain also enzyme myrosin (myrosinase)
which hydrolyze these glycosides.
Properties of Mustard oil :
1.Irritant for mucous membrane
2.Volatile
3.Pungent
4.Characteristic odor
The uses of Mustard seeds : counter irritant
rubefacient, condiment, emetic in large doses.
Drug :Acne aid soap®- Agis
Treatment of Acne .
Sinapine : alkaloids – alkaloidal amine group (protoalkaloid
properties of Acrinyl isothiocynate.
1.Less irritant than allyl isothiocynate.
2.Less volatile.
3.Odorless.
4.Pungent.
Uses of white mustard seeds
Condiment, carminative, counter irritant, emetic
Organic sulfur drugs
Garlic cloves :
Characteristic odor of Garlic
Allicin : yellow liquid responsible for the odor of
Garlic.
Uses :
1.Anti-bacterial
2.Anti-hyperlipidemic activity
HDL
3.anti-histaminic
4.anti-coagulant
5.Immune system stimulant.
** Coated tablet and capsules
stomach acid
inactivates alliinase enzyme.
Cyanogenic glycosides
Group glycosides which widely distributed between the members
of Rosaceae family.
They gave with hydrolysis HCN (Hydrocyanic acid)
They derived from nitrile of mandelic acid.
Cyanosides like :
1. Amygdalin :
a. Bitter almond seeds.
b. Apricots seeds.
c. Plums seeds.
d. Peaches seeds
2. Prunasin : present in Wild Cherry bark (( Prunus sertina))
Linmarin : Linseeds
The plants contain enzyme emolsin which produce during
hydrolysis two enzymes
1. Amygdalase hydro. Amygdalin.
2. Prunase hydro.Prunasin.
Flavonoids
Large group of glycosides which widely distributed in the plants
kingdom and in all plants parts (leaves, roots, rhizomes,
fruits peels)
Various colors in flowers( yellow, orange, red, purple.)
They are benzo-gama-pyrone derivatives.
Their chemical structure based on (C6 C3 C6 ).
The general uses of Flavonoids and Flavonoid glycosides.
1. Increase elasticity of blood vessels specially Rutin and
hesperidin which known as vitamin (p)
2. Anti inflammatory activity like Taxifolin
3.
4.
Anti spasmodic activity like Thyme and sage flavonoids.
Cytostatic activity.
Classification of Flavonoids according to the main nucleus
Main nucleus
flavonoids
Flavonoids glycosides
Flavonol unsaturated
yellow
quercetin
Quercitrin
Rhamnoglucoside
Flavone (unsat)
Yellow
Diosmetin
Vitexin
Flavanone (satur)
colorless
Hesperitin
Naringin
** C.G (Cardiac glycosides) : group of glycosides which has powerful action on
cardiac muscles (cardiac muscle stimulant).
C.G glycone part consist of one , two, three monosaccharide units or more similar or
different
Aglycone part has steroidal nucleus
cyclopentanoperhudrophenanthrene
B. glycone part of C.G always attached at C-3 position of aglycone part
classification
1. cardenolide (one double bond, lactone ring) :
Has five member lactone ring (unsaturated) attached at C17 B position of steroidal
nucleus.
2. Bufadienolide: (contain two double bonds, lactone ring)
Has six member ( unsaturated ) lactone ring attached at C-17
alpha – position
What is important for activity of C.G :-
1) The presence of hydroxyl group in C14 position makes the glycoside very
active and gives rapid action in the body, but if we change it to (H+) group
the drug will be inactive or less
active.
2) The presence of Alpha & Beta unsaturated lactone ring increases the
activity of C.G, but if
we make it saturated the C.G will lose its
activity.
3) The ring junctions Cis, Trans, Cis make the nucleus very stable so more
active.
4) The sugar part increases absorption and distribution of C.G in the body
S.P : Glucose, Rhamnose, Cymarose, Digitoxose
Examples of Cardenolides
1) Digitalis glycosides
Digoxin
Digitoxin
Gitoxin
2) Strophanthus gratus C.G :
Oubain
3) Strophanthus Kombe glycoside :
K- strophanthin
Bufadienolide example
Squill bulb glycoside
Scillaren
** Chemical tests :1) Keller Kiliani test : C.G + CH3COOH + H2SO4 + FeCl3
2) Legal test : C.G + pyridine sodium nitroprusside
*Uses :
1-CHF
brown
Red to pink colour
2- arrhythmias
* General properties of C.G :
taste
1- Amorphous powder
2-bitter
3- sol. In H2O
4-Insol. In Org. solvents
5- Very toxic compounds
6- Odorless
dig. Bind specific antibody
Tannins
• Complex natural organic compounds,
polyphenolic, polyhydroxy benzoic acid
derivatives or Flavanol derivatives.
• Widely distributed in the nature (leaves, barks,
immature fruits but, they disappear during
ripening process).
• They protect the plants from herbivorous
animals, insects, bacteria and others specially
during growth, like in new leaves which contain
high percentage of tannins.
• Some of them have low molecular weight but,
most of them have very large molecular weight.
Physico_chemical properties
1. They form colloidal solutions with water.
2. Non crystalline substances.
3. Their aqueous solution is acidic.
4. They have sharp puckering taste.
5. They have astringent property.
6. They precipitated by: alkaloids, gelatin, salts of
heavy metals, proteins (enzymes).
Tannins are classified into:
1.True tannins (hydrolysable)+ (nonhydrolysable).
2. Pseudo tannins.
Classification of tannins:
1)True tannins:
(a)Hydrolysable group:
1- Hydrolyzed by acids or enzymes (Tannase).
2- They are esters of a sugar (β-D-glucose) with
one or more trihydroxybenzene carboxylic
acid.
3-The tannins which derived from Gallic acid
called Gallo-tannin or glucogallin like in
Rhubarb rhizomes, Clove buds, Bearbers
leaves.
4- tannis which derived from ellagic acid called
ellagotannin or glucoellagin like in Pomegranate
roots bark and Eucalyptus leaves (which also
contain Tannic acid which is Gallotannin).
5- They form (H.T) with FeClз dark blue color.
(b) Non hydrolysable group of tannin, condensed
tannins or called proanthocyanidin tannins:
1- has resistance to hydrolysis by acids or
enzymes.
2- they are Flavanol derivatives:
1) Flavan-3-ol like catechin
2) Flavan-4-ol like leucocyanidin
3- they are founded:
In barks like: Cinnamon (Phlobatannins),
Cinchona (Cinchotannin), Wild cherry.
In seeds: Cacao, Cola (Colacatechin).
In leaves: Tea.
4- they produce dark green color with FeClз.
5- they produce Catechol with HCl(conc.) and with
vannillin_HCl reagent.
2) Pseudo tannins:
1- they have low molecular weight.
2- they occur:
as Gallic acid like in Rhubarb rhizomes.
as catechin like in Cacao, Acacia.
as chlorogenic acid like in coffee.
The general uses of tannins:
1)Anti diarrhea .
2) Anti bacterial .
3) Antidote in case of poisoning from alkaloids
and heavy metals .
4) Haemostatic .
5) Mild diuretic .
6) Leather industry .
7) Astringent for inflammated mucous membrane
8) Stomachic .
Chemical tests:
1) With FeClз :
(a) H.T→ dark blue
(b) Non H.T → dark green
2) ppt. with alkaloids, gelatin, proteins, and salts
of heavy metals like lead acetate, copper
acetate.
3) With H2SO4 → yellow
4) Vanillin_HCl reagent → red to pink color.