Al-kitab university

College of pharmacy

Pharmacognosy II lec.1

glycosides

INTRODUCTION

Many plant secondary metabolites in nature occur as glycosides . In plants,

glycosides are derived mostly from postmodification of the secondary metabolites
catalyzed by plant enzymes, glycosyltransferases. Further modifications of the
glycosides, such as oxidation, acylation, and degradation, take place frequently .
While there remains much to uncover on the physiological roles of these water-
soluble metabolites in plants, what is known is that they are stored and transported
within the plant tissue and may play an important role in signaling, regulation of
growth and development, and also in an allelopathy (biological phenomenon where
one plant inhibits the growth of another). They are also important in the plant’s
defense system against pathogens and herbivores. In many instances, glycosides
are produced as an answer to the environmental conditions, such as abiotic
(humidity, soil composition, sunlight, temperature) or biotic factors (e.g., plant
herbivores, coexisting plants).

Glycosides are organic natural compounds comprised of two chemically and

functionally independent parts; the aglycone (genin) and the glycone (saccharide)
parts. In a glycoside, the saccharide part (X) is linked to the aglycone (A) portion
by a glycosidic bond .

The glycosidic bond is mostly unstable and susceptible to hydrolysis (by diluted
acids or by enzymes, e.g., β-glucosidases). Accordingly, the types of glycosidic
linkages are classified as:

● O-glycosides (if the glycosidic bond is via oxygen); the most abundant form in
plants

● C-glycosides (linkage via a carbon); this type of linkage is resistant to hydrolysis

● S-glycosides (linkage via a sulfur; aglycone must have —SH group) present in
glucosinolates (thioglycosides)

● N-glycosides (linkage via a nitrogen; aglycone must have —NH group) present
in nucleosides.

The glycone is most frequently a monosaccharide, the most common being glucose
(a glycoside yielding glucose is called a glucoside). Other frequently occurring
glycones are L-rhamnose, L-fructose, L-arabinose, and D-xylose. The sugar unit
can also be a di-, tri-, or tetrasaccharide (e.g., in cardiac glycosides). The
configuration of the anomeric carbon of the glycone can exist as α or β
diastereoisomer with the β-forms being most common and active.

The overall effect of glycosides is dependent on their two components; the

aglycone portion primarily influences the therapeutic direction, while the
saccharide part (sugar chain/s) increases water solubility, pharmacokinetics, and
pharmacodynamics properties. The glycosidic linkage (normally β-linked in active
plant glycosides) is resistant to human digestive enzymes and hence glycosides are
often poorly absorbed from the digestive tract. They usually travel to the distal
ileum or large bowel. Here, microbial activity forms the aglycone, which is less
polar and can be absorbed into the bloodstream.

Medicinal importance of glycosides

 Source of analgesics e.g., gaultherin source of methylsalicylate ‘a hydrolytic

product

 Anti rheumatic: e.g., salicin.

 Anti-inflammatory: e.g., the glycoside glycyrrhizin. Also has demulcent,

expectorant and antispasmodic action.

 Cardiac drugs: e.g., digitalis glycosides, strophanthus, squill.

 Laxatives: e.g., anthraquinone glycosides of senna, aloes, rhubarb, cascara,

frangula.

 Counter irritants e.g., thioglycosides and their hydrolytic products ‘allylisothio

cyanate’

 Reduce the capillary fragility e.g., flavonoidal glycoside rutin.

 More recently as an anticancer agent e.g., amygdalin

Physical & chemical properties

Structures are diverse, however; Most glycosides are water soluble and soluble in
alcohols. Either insoluble or less soluble in non polar organic solvents. More sugar
units in a glycoside lead to more solubility in polar solvents. Glycosides do not
reduce Fehling’s solution, but when are susceptible to hydrolysis give reducing
sugars.

Classification

Glycosides can be classified by the glycone (type of sugar), by the type of

glycosidic bond, by the aglycone and by pharmacological action.

a).By glycone

If glucose, then the molecule is a glucoside;

If fructose, then the molecule is a fructoside;

If glucuronic acid, then the molecule is a glucuronide; etc.

Types of linkages;-

 C-linkage/glycosidic bond, where the sugar molecule is linked to carbon atom-

are non-hydrolysable by heating with dilute acids/alkalis. hydrolyzed by

oxidative hydrolysis with FeCl include some anthraquinone glycosides such as
cascarosides, aloin and some members of the flavones type of glycosides.
 O-linkage/glycosidic bond. These are very common in higher plants, e.g senna,
rhubarb.

 N-linkage/glycosidic bond- glycosylamines, nucleosides.

 S-linkage/glycosidic bond- thioglycosides, e.g, sinigrin and sinalbin.

By aglycone-

The classification is according to the chemical nature of the aglycone. For purposes
of biochemistry, pharmacognosy and pharmacology, this is the most useful
classification.

The following are various groups depending on aglycone type:

1. Aldehyde glycosides- e.g, vanillin

2. Alcoholic glycosides- e.g, salicin

3. Phenolic glycosides- the aglycone is a simple phenolic structure e.g, arbutin.

4. Anthraquinone glycosides- where aglycone group is a derivative of
anthraquinone.

5. Cardiac glycosides aglycone part is a C27 steroidal nucleus.

6. Coumarin and furanocoumarin glycosides- the aglycone is coumarin or its

derivative.

7. Cyanogenic glycosides- the aglycone contains a cyanide group, e.g ,

amygdalin.
8. Flavonoid and flavonol glycosides- the aglycone is a flavanoid.

9. Isothiocyanate glycosides

10. Saponins glycosides These compounds give a permanent soapy froth when
shaken with water.

11. Others e.g Steviol, quassia (under terpenoids) glycosides. Steviol glycosides
have steviol as the aglycone part
By pharmacological action

According to the physiological or pharmacological activity, e.g.

Laxative, Cardiotonic, analgesic, anti-inflammatory glycosides, etc

Stability of glycosides

Acid hydrolysis:

 Acetal linkage between the aglycone and glycone less stable than that between
two individual sugars within the molecule.

 All glycosides are hydrolysable by acids (except C-glycosides).

 Glycosides containing 2-deoxy sugars are more unstable towards acid hydrolysis
even at room temperature.

 C-glycosides are very stable (need oxidative hydrolysis).

 Enzymatic hydrolysis is specific. For each glycoside there is a specific enzyme

that exerts a hydrolytic action on it.

 The same enzyme is capable of hydrolyzing different glycosides, but α and β

sterioisomers of the same glycoside are usually not hydrolysed by the same
enzyme.

 Emulsin is found to hydrolyze most β-glycoside linkages, those glycosides

attacked by emulsin are regarded as β-glycosides.
 Maltase and invertase are α-glycosidases, capable of hydrolyzing α-glycosides
only

Qualitative tests depending on the aglycone

Steroidal or cardiac glycosides: Give +ve Liebermann’s test (steroidal structure).

Anthraquinone aglycones: Give +ve Borntrager’s test, characteristic reddish
coloration with alkalis. Flavonoidal glycosides and/or aglycones: Characteristic
colors with, NH4OH, AlCl3, FeCl3. Cyanogenetic glycosides give upon
hydrolysis, hydrocyanic acid which can be tested by changing Na picrate paper
(yellow) to red color. Qualitative tests depending on the aglycone Sulphur
containing glycosides give black precipitate of silver sulphate upon treatment with
AgNO3 solution.

General methods of isolation

Extraction of glycosides from plant material (previously dried and properly stored
to avoid decomposition of glycosides by plant enzymes) is usually performed with
the use of polar solvents (water, hydro-alcoholic solutions, and alcohols). The most
used extraction methods are percolation or maceration, Soxhlet extraction, or
special processes,e.g., pressurized liquid extraction (PLE/ASE), ultrasound-
assisted or microwave-assisted extraction (UAE or MAE) . Isolated glycoside
fractions are subsequently purified by the use of solvent/solvent partitioning
methods to remove chlorophylls or other pigments (water/hexane or
water/chloroform are used), separated by precipitation or adsorption methods
(column/planar chromatography) and then recrystallized.

Assist.lect. Mohammed A. Ezghayer