Transcript Intro-Sulphur

Glycosides
1
• 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
2
• 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)
3
• 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.
4
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
5
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
6
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.
7
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.
8
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
9
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.
10
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.
11
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).
12
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
13
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
14
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)
15
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
16
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
17
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
18
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).
19
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.
20
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
21
• 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
22