PHARM. DChemical Pharmacognosy- I

Lecture 17April 4th, 2011

GLYCOSIDESINTRODUCTION, CLASSIFICATION

M. Ahsan Khalid, B.Pharm, Pharm. DM.Phil Scholar (RIPS/RIU)

HIPS-HUKIC

In chemistry, glycosides are certain molecules in which a sugar part is bound to some other part. Glycosides

play numerous important roles in living organisms.

Many plants store important chemicals in the form of inactive glycosides; if these chemicals are needed, the

glycosides are brought in contact with water and an enzyme, and the sugar part is broken off, making the

chemical available for use. Many such plant glycosides are used as medications. In animals (including humans),

poisons are often bound to sugar molecules in order to remove them from the body.

Formally, a glycoside is any molecule in which a sugar group is bonded through its anomeric

carbon to another group via an O-glycosidic bond or an S-glycosidic bond;

OCH2OH

OHOH

OH

OH+ CH3OH

OCH2OH

OH

HOOH

OCH3 Glycosi

dic bond

H

+ H2O

-D glucopyranose

Mehtyl -D glucopyranose

OH on the anomeric carbon is replaced by an OR group, such acetal is called glycoside

The sugar group is then known as the glycone and the non-sugar group as the aglycone or genin part of the

glycoside. The glycone can consist of a single sugar group (monosaccharide) or several sugar groups

(oligosaccharide).

CLASSIFICATION

We can classify glycosides by the glycone, by the type of glycosidic bond, and by the aglycone.

1- BY GLYCONE

If the glycone group of a glycoside is glucose, then the molecule is a glucoside;

if it is fructose, then the molecule is a fructoside;

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

In the body, toxic substances are often bonded to glucuronic acid to increase their water solubility; the resulting

glucuronides are then excreted.

2- BY TYPE OF GLYCOSIDIC BOND

Depending on whether the glycosidic bond lies "above" or "below" the plane of the cyclic sugar molecule,

glycosides are classified as α-glycosides or β-glycosides respectively.

Some enzymes such as α-amylase can only hydrolize α-linkages; others, such as emulsin, can only affect β-

linkages.

3- BY AGLYCONE

Glycosides are also classified according to the chemical nature of the aglycone. For purposes of biochemistry

and pharmacology, this is the most useful classification.

i- Alcoholic glycosides

An example of an alcoholic glycoside is salicin which is found in the genus salix.

Salicin is converted in the body into salicylic acid, which is closely related to aspirin and has analgesic,

antipyretic and antiinflammatory effects.

ii- Anthraquinone glycosides

These glycosides contain an aglycone group that is a derivative of anthraquinone.

They are present in senna, rhubarb and aloes; they have a laxative effect.

iii- Coumarin glycosides

Here the aglycone is coumarin.

An example is apterin which is reported to dilate the coronary arteries as well as block calcium channels.

Those obtained from dried leaves of Psoralia corylifolia have Main glycosides psoralin and corylifolin.

iv- Cyanogenic glycosides

In this case, the aglycone contains a cyanide group, and the glycoside can release the poisonous hydrogen

cyanide if acted upon by some enzyme.

An example of these is amygdalin from almonds.

Cyanogenic glycosides can be found in the fruits (and wilting leaves) of the rose family (including cherries,

apples, plums, almonds, peaches, apricots, raspberries, and crabapples).

v- Flavonoid glycosides

Here the aglycone is a flavonoid. This is a large group of flavonoid glycosides. Examples include:

Hesperidin (aglycone: Hesperetin, glycone: Rutinose)

Naringin (aglycone: Naringenin, glycone: Rutinose)

Rutin (aglycone: Quercetin, glycone: Rutinose)

Quercitrin (aglycone: Quercetin, glycone: Rhamnose)

Among the important effects of flavonoids are their antioxidant effect. They are also known to decrease

capillary fragility.

vi- Phenolic glycosides

Here the aglycone is a simple phenolic structure.

An example is arbutin found in the Common Bearberry Arctostaphylos uva-ursi. It has a urinary antiseptic

effect. Rutin found in rooibos tea.

vii- Saponins

These compounds give a permanent froth when shaken with water.

They also cause hemolysis of red blood cells.

Saponin glycosides are found in liquorice. Their medicinal value is due to their expectorant effect.

viii- Steroidal glycosides or cardiac glycosides

Here the aglycone part is a steroidal nucleus.

These glycosides are found in the plant genera Digitalis, Scilla, and Strophanthus.

They are used in the treatment of heart diseases e.g. congestive heart failure (historically as now recognised

does not improve survivability; other agents are now preferred] and arrhythmia.

ix- Steviol glycosides

These sweet glycosides found in the stevia plant Stevia rebaudiana bertoni have 40-300 times the sweetness of

sucrose.

The two primary glycosides, stevioside and rebaudioside A, are used as natural sweeteners in many countries.

These glycosides have steviol as the aglycone part. Glucose or rhamnose-glucose combinations are bound to the

ends of the aglycone to form the different compounds.

x- Thioglycosides

As the name implies, these compounds contain sulfur.

Examples include sinigrin, found in black mustard, and sinalbin, found in white mustard.

SUGARS IN GLYCOSIDES:

The sugar portion:

1- It may be molecule of a monosaccharide e.g. D-glucose or L-rhamnose.

- or composed of 2 or more sugars, forming a di-or oligosaccharide chain e.g. purpurea glycoside

- has a tetrasaccharide attached to digitoxigenin e.g. Digitoxigenin -O-(digitoxose)3-O-glucose .

2- In certain cases, the oligosaccharide portion is branched as in the steroidal saponin, digitonin where there is

a branched pentasaccharide chain.

3- Sometimes, two monosaccharide units are attached at two different positions in the aglycone molecule

Effect of the sugar portion on solubility of the glycoside:

Salicin, with one glucose unit, is soluble in ether, while glycosides with a larger sugar portion are more soluble

in alcohol or aqueous alcoholic solvents.

Effect of the sugar on susceptibility of the glycoside to acid hydrolysis:

Generally 2-deoxy sugars can be hydrolyzed easier than 6-deoxysugars, and the latter more easily than normal

sugar. Thus milder conditions can be chosen to hydrolyze the glycoside involving 2-deoxysugars, without

affecting the others .

Solubility of glycosides:

The presence or absence of various polarity contributing functional groups in the structure of the aglycone

portion, would contribute to the degree of solubility in a given solvent e.g. thioglycosides are soluble in water

partly because of the ionic sulfate residue.

The number and kind of monosaccharide units present in the sugar portion would contribute a certain polar

character and thus contributing to the degree of solubility in polar solvents.

Hydrolytic cleavage and stability

1-Acid Hydrolysis:

Glycosides can be hydrolyzed by heating with a dilute acid, where by the glycosidic linkages are

cleaved.

Glycosidic linkages involving different kinds of sugars are hydrolyzed with different degrees by acid

hydrolysis

e.g. 2-deoxysugars are hydrolyzed easier than 6-deoxy-sugars, which is still easier than normal sugars.

- If there is a di-or an oligosaccharide unit in the molecule, it is practically impossible to cleave one unit of

sugar at a time with acid hydrolysis.

When stepwise cleavage of monosaccharide units is needed, specific enzyme hydrolysis must be used.

C-glycosides are more resistant to acid hydrolysis than O-glycosides i.e. they do require more vigorous

conditions.

2- Enzymatic Hydrolysis:

Glycosides can be hydrolyzed by appropriate enzymes, which are usually found in the same plant, in

separate compartments.

The glycosidic linkages involving b-D-glucose as well as most b-glycosides can be hydrolyzed by

various b-glycosidases.

Stepwise hydrolysis of monosaccharide units is possible using specific enzyme.

a- Digitalidase, in Digitalis purpurea

b- Lanatosidase present in D. lanata

c-Strophanthibiase acts upon K-strophanthoside to give cymarin.

It is thus clear that enzymatic hydrolysis is specific. During extraction or isolation of glycosides appropriate

measures should be taken to prevent the cleavage of glycosides by the enzymes that may be present in the same

plant.

3- Effect of Alkali:

- Alkalies do not , generally, cleave glycosidic linkages.

- Ester groups in the glycosides may be cleaved e.g. the acetyl- group in lanatosides or the sulfate group in

thioglycosides ... etc.

- Degradation may occur in the aglycone or in the sugar portion by alkali.

The lactone ring at C17, in cardiac aglycones is opened by strong alkalies, with subsequent loss of the

cardiotonic activity, this change is irreversible on addition of acids.

Extraction and Isolation

1- Acidic conditions should be avoided during extraction.

2- Inactivation of the enzymes:

a- Boiling alcohol for 10-20 minutes.

b- Boiling with acetone.

c- Low temperature i.e. in the cold.

d- precipitates the enzymes with ammonium sulfate.

e- Freeze-drying.

f- A special drying procedure such as a short heat treatment.

Extraction Procedures:

Generally, the glycoside is extracted from the crude drug with Alcohol.

-Adding basic lead acetate to the alcoholic extract causes the impurities to precipitate.