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•Glycosides are non-reducing organic compounds that on hydrolysis with acids or enzymes yield:
–A sugar part (or glycone, formed of one or more sugar units).
–A non-sugar part (or aglycone, also called genin).
- The two parts are linked by glycosidic (acetal) linkage
- Their names frequently ends with -side
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• Chemistry
• Glycosides are considered as acetals or sugar ethers where the –OH group of the anomeric carbon (i.e. at C-1 of the aldose sugar) is replaced by a moiety possessing a nucleophilic atom such as: O, S, N or C in the form of carbanion to give the corresponding O-, S-, N- or Cglycosides.
• Glycosides are non-reducing compounds (do not reduce
Fehling’s solution) unless the aglycone portion contains a reducing group (e.g. K-strophanthoside).
CHO
CH
2
OH
CH
2
OH
H
H OH
O
H H
H OH
OH
OH
HO H OH OH
OH O
H OH OH
OH
CH
2
OH  or

-
Glucose Hemiacetal form
OH
CH
2
OH
O
OH
OH
H
OH
Hemiacetal form
H nucleophile
OH
CH
2
OH
O
OH
OH
H
OR
Acetal
(Glycoside)
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• The common linkage between the sugar part and the aglycone is an oxygen linkage connecting the reducing group of a sugar and an alcoholic or a phenolic hydroxyl group of the aglycone to give O-glycosides.
• Since the sugars exist in isomeric  - and  -forms, both
 - and  -glycosides are theoretically possible, but most of the naturally occurring glycosides are of the  -type.
• The most common sugar in glycosides is  -D-glucose, but other sugars (like pentoses and deoxy-hexoses), or sugar derivatives (e.g. uronic acids such as glucuronic acid in glycyrrhizin) are also found.
The role of the sugar moiety in glycosides is :
To help in stabilization and solubilization of the molecule;
To carry the aglycone to the site of action.
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They are classified according to:
1) Atom from the aglycone involved in the glycosidic linkage:
• Aglycone- O- Sugar O-glycosides
• Aglycone- C- Sugar C-glycosides
• Aglycone- S- Sugar S-glycosides
• Aglycone- N- Sugar N-glycosides
2) Number of sugars:
• One sugar monosides
• Two sugar Biosides
• Three sugars Triosides e.g. Salicin.
e.g. Diosmin.
e.g. Digoxin.
3) Nature of the glycoside:
• Primary glycosides: Originally present in the plant e.g.
Purpurea A
• Secondary glycosides: Resulted from removal of one sugar from the primary glycosides e.g. Digitoxin
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4) Type of the glycosidic linkage:
  - glycosides
  - glycosides
5) Botanical source:
• Digitalis glycosides
• Senna glycosides.
6) Therapeutic use:
• Analgesic glycosides.
• Purgative glycosides.
• Cardiac glycosides.
7) Chemical nature of the aglycone:
• Flavonoidal glycosides.
• Steroidal glycosides.
• Anthraquinone glycosides.
• Cyanogenic glycoside
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:





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• Acids split sugars from the aglycones.
• The acetal linkage is more readily cleaved than the linkage between the individual sugars of the sugar chain.
• C-glycosides are resistant to acid hydrolysis.
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• Hydrolysis of ester groups e.g. Lanatoside A to Purpurea A
• Opening of lactone rings e.g. Cardiac glycosides.
• Racemization of sugars
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– Split the sugars stepwise starting from the terminal sugars.
– All plants producing glycosides have enzyme that can hydrolyze these glycosides.
– Enzymes are specific for the type of glycosidic linkages:
• Emulsin can hydrolyze  - glycosides
• Invertase can hydrolyze  - glycosides
• Myrosinase can hydrolyze S -glycosides.
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o Because of the wide range of physical and chemical properties of glycosides and other constituents associated with them, no common general method for their isolation is recommended. o Water, methanol, water-ethanol and ethanol are the most common solvents for extraction of glycosides.
o Precautions before extraction
1) Deactivation of enzymes: o Drying for 15-30 min at 100 o C followed by slow drying at a low temperature.
o Dipping the fresh material into boiling water or boiling
alcohol for 10-20 min.
o Carrying out the extraction at very low temp.
o Freeze-drying of the plant material before extraction
(lyophilization).
o Carrying the extraction in the presence of (NH
4
)
2
SO
4
.
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2) Maintenance of neutral conditions: o Neutral pH should be maintained before and during extraction because:
-Acidity may result in hydrolysis. This is overcome by addition of little CaCO
3
(cautiously).
- Mild alkalinity may sometimes produce racemization.
3) Defatting of fat-rich organs before extraction (e.g. seeds as in linseed) : o High amounts of lipids hinder glycoside extraction.
Defatting is usually carried out with petroleum ether (nhexane).
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
Salix species (Willow bark).

Primary alcoholic and Phenolic glycoside (monoside).

Analgesic- Antipyretic- Antiinflammatory.
CH
2
OH
O
Saliretin
HOH
2
C
+
Glucose
Acid
CH
2
OH
Enzyme
O-glc
CH
2
OH
OH
Saligenin
(Salicyl alch.)
+
Glucose
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 Source: Uva Ursi (Bearberry leaves).
 Nature: Primary Phenolic glycoside (monoside).
 Uses: Diuretic- Bactericidal, UT infections, and skin

 lightening preparations (topically, inhibition of melanin synthesis).
OH
OH
Hydrolysis
OH
Hydroquinone
+ Glucose
O-glc
Arbutin
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
Vanilla pods.

Flavouring agent, and Spray reagent.
Glucovanillin Vanillin
CHO CHO
Enzymatic Hydrolysis
+ Glucose
OCH
3
OCH
3
O-glc OH
Green vanilla pods
Bitter in taste
Odourless
Brown vanilla pods
Sweet in taste
Vanilla odour
In green pods in fermented pods (brown, dry) 15

Eugenol
(clove oil)
CH
2
-CH=CH
2
OCH
3
OH
KOH
Iso-eugenol
CH=CH-CH
3
OH
OCH
3
Oxidation
Vanillin
Guaiacol
(from wood, expec)
OCH
OH
CH=CH-CH
2
OH
3
Coniferin
(lignin of confers)
CHCl
3
+ NaOH
Reflux
Vanillin
H
2
SO
4
/K
2
Cr
2
O
7
Vanillin
OCH
3
O-glc
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Most vanillin is now prepared from phenol or lignin (cheap sources)

 Cyanogenic glycosides (Cyanogentic or
Cyanophore Glycosides) are O-glycosides yielding
HCN gas on hydrolysis .
 They are condensation products of HCN to a carbonyl compounds (Cyanohydrin).
R
R
C O
HCN
R
CN
Glycosylation
C
R
Unstable
OH
R
CN
C
R
Stable
O-Sug
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1- Amygdalin
 Source: bitter almond.
 Structures: It is a bioside of mandelonitrile.
HCN +
Benzaldehyde
CHO
O H
CH
CN
Mandilonitril
(1-6)
 linkage
O glc glc
CH
CN
Amygdalin
Amygdalase
O glc
CH
CN
Prunasin
Prunase
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 Source: Linseed (Linum usitatissimum,
Linaceae).
 Structures:
It is the glycosidic derivative of the cyanohydrin of acetone.
H
3
C O glc
C
H
3
C CN
 Uses of cyanophoric glycosides:
 Linamarin has a molluscicidal activity.
 Amygdalin is used for the preparation of
Benzaldehyde.
 Cyanogenic glycosides have role in cancer treatment
 (probable HCN toxicity).
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• Reduce plant material to small pieces and moisten with water.
• Incubate at temp. less than 45 0 C for 60 min. with the neck of the flask is stoppered and have suspended sodium picrate paper.
• The paper will turns brick red due to the release of HCN gas.
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Glucosinolates- Sulphur Glycosides
• They are S-glycosides widely distributed in family
Cruciferae.
• Sinigrin: In seeds of Brassica nigra (black mustard).
• Sinalbin: In Seeds of Brassica alba (white mustard).
S-Glc
H
2
C C
H
C
H
2
C
N-O-SO
3
K
Allylisothiocyanate
(pungent, volatile)
Sinigrin hydrolysis myrosinase
H
2
C C
H
H
2
C N C S + glucose + KHSO
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• Uses: Rubefacients, Counter irritants, and condiment.

Garlic
• It consists of the bulb of Allium sativum Fam. Liliaceae.
• The intact cells of garlic contain an odorless, sulfur- containing amino acid derivative (+)-S-allyl-L-cysteine sulfoxide , commonly known as alliin .
• Alliin is hydrolyzed by the effect of alliinase enzyme present in different cells after crushing into allicin (diallyl thiosulfinate).
• Allicin is responsible for the characteristic odor and flavor of garlic.
• Allicin is a potent antibacterial, antihyperlipidemic, and it inhibits platelet aggregation and enhances the blood fibrinolytic activity.
Alliin
O
S
COOH
H
NH
2
Alliinase
O
S
Allicin
S
+ H
2
O
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