Transcript Intro-Sulphur.ppt

Glycosides
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• Definition:
Introduction
•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
H
OH
H
HO
OH
H
H
OH
CH2OH
CH2OH H
O
..
O
H
OH
O
OH
H
OH
OH
OH
OH
OH
or -
CH2OH
Glucose
Hemiacetal form
CH2OH
CH2OH
O
OH
O
H
OH
OH
OR
OH
H
O
.. R
OH
H
OH
OH
Hemiacetal form
nucleophile
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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Classification
They are classified according to:
1) Atom from the aglycone involved in the glycosidic
linkage:
•
•
•
•
AglyconeAglyconeAglyconeAglycone-
O- Sugar
C- Sugar
S- Sugar
N- Sugar
O-glycosides
C-glycosides
S-glycosides
N-glycosides
2) Number of sugars:
• One sugar
• Two sugar
• Three sugars
monosides
Biosides
Triosides
e.g. Salicin.
e.g. Diosmin.
e.g. Digoxin.
3) Nature of the glycoside:
• Primary glycosides: Originally present in the plant
Purpurea A
e.g.
• Secondary glycosides: Resulted from removal of one sugar
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from the primary glycosides e.g. Digitoxin
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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Physical Characters:
Solids either amorphous or
crystalline.
Non volatile.
Usually bitter in taste.
Soluble in water and polar organic
solvents.
Reduce Fehling’s solutions only after
hydrolysis.
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Stability of Glycosides (reactions):
1- Effect of acid hydrolysis:
• 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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2- Effect of alkaline hydrolysis:
• Hydrolysis of ester groups e.g. Lanatoside A
to Purpurea A
• Opening of lactone rings
glycosides.
• Racemization of sugars
e.g. Cardiac
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3- Enzymatic hydrolysis:
– 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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Extraction and Isolation
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 oC 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 (NH4)2SO4.
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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 CaCO3 (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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Alcoholic and Phenolic Glycosides
1- Salicin
Source: Salix species (Willow bark).
Nature: Primary alcoholic and Phenolic
glycoside (monoside).
Uses: Analgesic- Antipyretic- Antiinflammatory.
CH2OH
CH2OH
O
Saliretin
HOH2C
+
Glucose
CH2OH
Enzyme
Acid
OH
Saligenin
(Salicyl alch.)
O-glc
+
Glucose
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2- Arbutin
 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
+ Glucose
OH
O-glc
Hydroquinone
Arbutin
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Aldehydic Glycosides
1- Glucovanillin
Source: Vanilla pods.
Uses: Flavouring agent, and Spray
reagent.
Glucovanillin
Vanillin
CHO
CHO
Enzymatic Hydrolysis
+ Glucose
OCH3
OCH3
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)
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Commercial Preparation of Vanillin
CH2-CH=CH2
Iso-eugenol
Eugenol
CH=CH-CH3
Vanillin
(clove oil)
KOH
Oxidation
OCH3
OCH3
OH
OH
CHCl3+ NaOH
Guaiacol
OCH3
(from wood, expec)
Vanillin
Reflux
OH
CH=CH-CH2OH
H2SO4/K2Cr2O7
Coniferin
Vanillin
OCH3
(lignin of confers)
O-glc
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Most vanillin is now prepared from phenol or lignin (cheap sources)
Cyanogenic Glycosides
 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
C
R
CN
R
O
HCN
C
Glycosylation
C
OH
R
Unstable
CN
R
O-Sug
R
Stable
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1- Amygdalin
 Source: bitter almond.
 Structures: It is a bioside of mandelonitrile.
O
HCN +
CHO
H
CH
CN
Benzaldehyde
Mandilonitril
(1-6) linkage
O
glc
glc
CH
O
CH
Amygdalase
CN
Amygdalin
glc
CN
Prunasin
Prunase
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2- Linamarin
 Source:
Linseed (Linum usitatissimum,
Linaceae).
 Structures:
It is the glycosidic derivative of the
cyanohydrin of acetone.
H3C
O
glc
C
H3C
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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Test for Cyanogenic Glycosides:
• Reduce plant material to small pieces and
moisten with water.
• Incubate at temp. less than 45 0C 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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Thioglycoside
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
Allylisothiocyanate
(pungent, volatile)
C
H2C
C
H
C
H2
N-O-SO3K
Sinigrin
hydrolysis
myrosinase
H2C
C
H
H2
C
N
C
S
+
glucose + KHSO4
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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, sulfurcontaining 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.
O
S
O
COOH
H
Alliin
NH2
Alliinase
S
S
+ H2O
Allicin
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