1-Glycosides intro. .pptx

GLYCOSIDES INTRO.
Assoc. Prof. Dr. Mostafa Mahmoud Hegazy

 content
 Definition
 some medicinal uses of glycosides
 Function in the plant
 Aglycones and sugar moiety
 Pharmacological activities
 Stability and hydrolytic cleavage
 Classification and nomenclature
 Extraction and isolation
 Quantitative Determination

Glycosides Dr. Mostafa Hegazy
Definition
Glycosides are non-reducing organic
compounds that on hydrolysis with
acids or enzymes yield:
1- A sugar part (or glycone, formed
of one or more sugar units).
2- A non-sugar part (or aglycone,
also called genin).

 Glycosides are non-reducing
compounds (do not reduce Fehling’s
solution) unless the aglycone portion
contains a reducing group (e.g. in K-
strophanthoside which contains an
aldehydic group).
 After hydrolysis the sugar part has
reducing characters.

Examples of some medicinal uses of glycosides
for treatment of
1-CHF as cardiac stimulants e.g. digoxin and
ouabain from Digitalis and Strophanthus
respectively.
2- Acute Constipation as laxative e.g.
sennosides and barbaloin from Senna and aloe
respectively.

3- Arthritis and muscle aches as
I- counter irritant e.g. sinigrin from
black mustard
II- analgesic e.g. salicin from Salix
4- Varicose vein and Hemorrhoids for
capillary fragility e.g. Rutin and
hesperidin from Citrus.
5- liver support and antiviral e.g.
glycyrrhizin from liquorice.

Function in the plant
Glycosides are considered as:
 Energy producers during seedlings through
hydrolysis of stored compounds.
 Detoxifying agents for many harmful substances that
are transferred to the barks, seed coats and fruits in
the form of glycosides.
 Stabilizers for labile substances.
 Decorative or attractive substances such as floral
pigments.
 Protectives against microorganisms and insects.

Aglycones
 Def.: These constitute the non-sugar moieties
of the glycosides
 Types acc. to glycosidic linkage: They
contain free -OH group (in O-glycosides),
free NH (in N-glycosides), free SH(in S-
glycosides)
 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.

Aglycones
 Types acc. to the stereo of the sugars:
sugars exist in isomeric - and -forms, both -
and -glycosides are theoretically possible, but
most of the naturally occurring glycosides are of
the -type
 Types acc. to aglycon chemical classes such
as: phenols, alcohols, flavonoids, steroids,
saponins, etc.
 They constitute the pharmacologically active
part of the glycosides.

The sugar moiety in glycosides consists of either :
1- A monosaccharide molecule (e.g. glucose,
rhamnose..etc),
2- Disaccharide molecule as gentiobiose.
3- An oligosaccharide
(e.g. trisaccharide as scillatriose, tetrasaccharide as in
purpurea glycoside A, or pentasaccharide as in saponins),
linked together in a chain.
Common sugar in glycosides is -D-glucose,
Other sugars (like pentoses and deoxy-hexoses)
Sugar derivatives (e.g. uronic acids such as glucuronic acid
in glycyrrhizin) are also found.

Sugar Attachment
The sugar moiety is attached to the aglycone part
mostly at :
one position (e.g. in monodesmosidic saponins), or
two different positions (e.g. in bidesmosidic
saponins).
Role of the sugar moiety in glycosides
 To help in stabilization and solubilization of
the glycoside molecule;
 To carry the aglycone to the site of action.

Pharmacological activities
The pharmacological action of glycosides is
mainly associated with and due to the
aglycone part.
Pharmacological activities such as
anticancer, anti-inflammatory,
immunomodulating, antihepatotoxic, antiviral,
analgesic, antipyretic, hypoglycemic, diuretic
as well as cardiotonic activities.
Activity not enough for the compound to
be a drug.

Activity not enough for the compound to
be a drug.
 Various flavonoids are inhibitors of enzymes
like monoaminooxidase (depression), protein
kinase C (inflammation) , tyrosine kinase
(many ex. cancer), and phosphodiesterase
enzymes (vasodilatation).
 e.g. arbutin is used as urinary antiseptic,
salicin as anti-rheumatic and analgesic, rhein
as anti-inflammatory, sennosides and
barbaloin as laxative digoxin and
lanatosides as cardiotonic

Glycosides Chemistry
 Glycosides are considered as acetals or
sugar ethers.
 Where the –OH group of the anomeric
carbon of hemiacetal (i.e. at C-1 of the
aldose sugar) is replaced by a moiety
possessing a nucleophilic atom such as:
OR, SR, NR or CR in the form of
carbanion to give the corresponding O-,
S-, N- or C-glycosides.

STABILITY AND HYDROLYTIC CLEAVAGE
Effect of acid hydrolysis
• The acetal linkage between the aglycone and sugar
part is more readily cleaved than the linkage
between the individual sugars of the sugar chain.
• Glycosides containing normal sugars are more
resistant to acid hydrolysis than those containing 2-
deoxy sugars.
• Drastic hydrolytic conditions may cause chemical
changes in the aglycone moiety.

EFFECT OF ALKALINE HYDROLYSIS
• Being acetals, glycosides are relatively stable to alkaline hydrolysis.
• Alkalis may modify:
• The aglycone e.g. strong alkalies open the lactone ring in case of
cardiac glycosides with loss of cardiotonic activity.
• The sugar part e.g. mild alkalies remove the acetyl group of
acetyldigitoxose in lanatosides.

EFFECT OF ENZYMATIC HYDROLYSIS
• Generally, a specific enzyme is required to hydrolyze a particular
glycoside.
• Although, certain enzymes (e.g. emulsin and myrosin) are
exceptions. Each of them hydrolyzes a considerable number of
glycosides.
• Emulsin hydrolyzes all β-linked glycosides.
• Myrosin hydrolyzes all Sulphur-containing glycosides: e.g. sinigrin in
black mustard.
• Yeast hydrolyzes all α-linked glycosides.

EFFECT OF ENZYMATIC HYDROLYSIS
• Generally, the enzyme is named after the type of sugar
• e.g. glycosides, which contain β-D-glucose, are hydrolyzed by β –
glucosidase.
• while those containing rhamnose require rhamnosidase for their
hydrolysis.

CLASSIFICATION AND NOMENCLATURE
• Glycosides may be classified in different ways according to:
• The chemical nature of their aglycones, into for example
alcoholic, ester, phenolic, flavone, anthraquinone, steroid,
lactone, monoterpenoid, diterpenoid, triterpenoid glycosides
etc…...
• The presence of a special functional group in the molecule
into aldehydic glycosides (aldehyde group), cyanophore or
cyanogenic glycosides (cyanide group), and thio- or
sulphated glycosides (thio group, -SH) etc…..

CLASSIFICATION AND NOMENCLATURE
• Their therapeutic properties such as
cardiac, urinary antiseptic and laxative
glycosides etc…..
• Their nature whether primary
(unchanged naturally occurring
compounds) or secondary glycosides
(that resulted from partial hydrolysis of
primary glycosides).

Nomenclature
They are generally named according to their botanical origin
e.g. salicin from Salix, sennosides from Senna etc…...
Properties
 They are colorless, solid, mostly bitter in taste (except
populin, stevioside, glycyrrhizin and neoastilbin that are
sweet).
 They are generally soluble in water and hydro alcoholic
solutions. Some glycosides are sparingly soluble in water
but soluble in ethyl acetate, acetone, chloroform and ether.
 They are non-reducing (do not reduce Fehling's solution).

Extraction and isolation
 no common general method for their
isolation is recommended.
 Because of the wide range of physical and
chemical properties of glycosides and other
constituents associated with them.
 Water, methanol, water-ethanol and ethanol
are the most common solvents for extraction
of glycosides.

Precautions before extraction:
I- Deactivation of enzymes
Glycosides are accompanied by their specific hydrolytic enzymes, these should
be deactivated before or during extraction to avoid their hydrolytic action,
particularly when fresh plant material is used.
Methods of enzymes deactivation:
 Drying for 15-30 min at 100 oC followed by slow drying at a low
temperature.
 Dipping the fresh material into boiling water or boiling alcohol for 10-20 min.
 Boiling the fresh plant material with acetone.
 Carrying out the extraction at very low temp.
 Freeze-drying of the plant material before extraction (lyophilization).
 Carrying the extraction in the presence of (NH4)2SO4.

II- Maintenance of neutral conditions
 Neutral pH should be assured before and during extraction because:
 Acidity may result in hydrolysis. This is overcome by addition of CaCO3.
 Mild alkalinity may sometimes produce racemization.
III- Defatting
 Defatting of fat-rich organs (e.g. seeds) before extraction.
 High amounts of lipids hinder glycoside extraction.
 Defatting is usually carried with petroleum ether

Purification of extracted glycosides
One / or most of the following steps is/ are recommended:
1-Addition of lead acetate solution to the extract in order to precipitate
the non-glycosidic constituents e.g. tannins, proteins, coloring substances
when associated with glycosides, excess lead can then be removed as lead
sulfide or lead phosphate by passing H2S or adding sodium phosphate to
the filtrate.
However, this is not recommended in case of flavonoid glycosides which
may be precipitated

2-Addition of solvent for precipitation or crystallization of
glycosides e.g.
by dissolving the extract in hydroalcoholic or alcoholic solution
and then adding acetone or ether to precipitate or crystallize out
the glycosides.
3-Chromatographic techniques such as CC or TLC are
commonly used for purification.

Quantitative Determination
I- Spectrophotometric methods:
1-By measuring UV absorption of stable color
developed when a specific reagent reacts with a
particular compound (analytical marker) .The
intensity of the color produced must obey Beer's law
(e.g. colorimetric determination of cardiac glycosides
after reaction with Baljet's or Kedde's reagents).
2-the UV absorption of the developed compound
containing a conjugated diene, where the UV
absorption is directly proportional to the concentration
of the compound.

II- Chromatographic methods:
 By using HPLC or GC techniques, where the area under the peak
corresponding to the specific compound is calculated and is directly
proportional to its concentration.
 The glycoside may be estimated in the intact form or after hydrolysis;
the aglycone part can be extracted with organic solvent (e.g. ethyl
acetate) and then determined by HPLC or GC. The sugar part
obtained in the aqueous layer can also be determined by GC after
silylation or by HPLC

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1-Glycosides intro. .pptx