Glycosides 2021 (Introduction)

1. Introduction
Ph.D.Ahmed Metwaly
Email: ametwaly@azhar.edu.eg
• Associate Professor of Pharmacognosy , faculty of Pharmacy, Al-Azhar
University
• Senior research fellow, Liaoning University of Traditional Chinese
Medicine, China (20118-2019)
• Visiting scholar, School of Pharmacy, University of Mississippi, USA (2012-
2014)

2. OBJECTIVES:
⮚Introduction
1. Definition & General characters
2. Function
3. Nomenclature
4. Classification
5. Occurrence and distribution
6. Chemical characters
7. Examples

3. ▪ Definition:-
Glycoside is a molecule that contains a
sugar (glycone) and another a glycone
part bonded via a glycosidic bond
▪ .

4. ▪ 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 C-glycosides.
▪ Non-reducing organic compounds that yield upon hydrolysis one or more sugars by the action of dil. acids,
alkalis or enzymes
▪ unless the aglycone portion contains a reducing group
(e.g. in K-strophanthoside which contains an aldehydic group
K-strophanthoside

5. Functions of glycosides in the plants

6. Medicinal uses of Glycosides

7. NOMENCLATURE OF GLYCOSIDES
⮚The trivial names have an “in” ending, and the names indicate the source
of glycoside, for example, digitoxin from Digitalis
⮚ The systematic names are usually formed by:
✔The chemical name of the aglycone precedes the name of the sugar.
✔The anomeric prefix (α- or β-) and the prefix (D or L) immediately
precede the sugar stem name.
✔Replacing the “ose” suffix of the parent sugar with “oside”.
Salicin is o-hydroxymethyl phenyl β-D-glucopyranoside.

8. CLASSIFICATION OF GLYCOSIDES

9. CLASSIFICATION ACCORDING TO THE CHEMICAL
NATURE OF THE AGLYCONES

10. (α - and β- GLYCOSIDES)
✔Chemically glycosides are acetals or sugar ethers.
✔Because of the cyclic structure of the sugar, two anomers of the glycoside (α
and β) and both are found in Nature.
✔Isomeric glycosides may be prepared synthetically
e.g. from glucose and methyl "alcohol which give α - and β-methylglycosides

11. SUGARS IN GLYCOSIDES
The sugars found in glycosides may be:
1-A monosaccharide e.g. glucose (most common) in salicin or rhamnose in oubain.
2-An oligosaccharides e.g.tetrasaccharide as in purpurea glycoside A
❖The role of sugar in glycosides:
1- To affect the degree of polarity and Consequently the solubility and stabilization.
2- To carry the aglycone to the site of action.

12. STABILITY AND HYDROLYTIC CLEAVAGE
1-Acid hydrolysis:
⮚The acetal linkage is more readily cleaved than the linkage between the individual sugars of
the saccharide portion.
⮚ Some glycosides are much more resistant to acid hydrolysis
⮚2- deoxy sugars (cardiac glycosides) are easily hydrolyzed by weak acids at room temperature.
2-Alkali hydrolysis:
✔Glycosides being acetals, they are stable to alkali hydrolysis
✔Different degrees of alkalinity may affect on glycoside differently
e.g.: The lactone ring of the cardiac glycosides is opened with the loss of cardiotonic activity.
e.g.: The acetyl group attached by ester linkage to the sugars may be removed.

13. 3-ENZYMATIC HYDROLYSIS:
⮚ In plant tissues most glycosides are associated with enzymes, which are classified as glycosidases.
⮚ In most cases the glycoside is easily hydrolyzed by an enzyme which occurs in the same plant tissue,
but in different cells.
⮚ A specific enzyme may be found in plants which hydrolyzes only a single glycoside.
⮚ Glycosides are synthesized and hydrolyzed in plants by specific enzymes:
❖ Exception
1-The enzyme emulsin hydrolyzes β –linked glycosides.
2-The enzyme maltase hydrolyses α-linked glycosides.
3- Myrosin hydrolyzes all S-containing glycosides e.g.
Sinigrin allyl isothiocyanate +glucose + KHS04

14. Digitoxose- Digitoxose-Digitoxose- Glucose
Purpurea A
Digitoxose- Digitoxose- Acetyl Digitoxose- Glucose
Lanatoside A (glycone, sugar part)
Aglycone, non sugar part
Deoxy sugar
Alkaline Hydrolysis
Enzyme Hydrolysis
Acid Hydrolysis

15. AGLYCONES
⮚They are the non - sugar portions of the glycosides.
⮚They vary in their chemical constitutions.
⮚They constitute the pharmacologically active part of the glycosides.
⮚According to the nature of the aglycon, glycosides are classified into two main groups:
a-Heterosides: The aglycone consists of a non- sugar e.g. rutin and digitoxin.
b-Hallosides: Glycosides in which the aglycon is a sugar e.g. lactose and heparin.

16. PROPERTIES OF GLYCOSIDES
✔They are usually colorless, solid, non-volatile and crystalline.
✔ Most of them are bitter except populin has a sweet taste.
✔Solubility :
⮚Generally, they are soluble in H2O and hydro alcoholic.
⮚ Glycosides are more soluble in H2O than their aglycones due to the hydrophilic nature of the sugar.
⮚Some glycosides are also soluble in ethyl acetate, CHCl3.
⮚The higher the sugar content, the less soluble in organic solvents.

17. EXTRACTION AND ISOLATION OF GLYCOSIDES:
⮚Because of the wide range of physical and chemical properties of
glycosides and other constituents associated with them no
common general method for their preparation is recommended.
⮚H2O mixed with different proportions of EtOH is the most common solvent for
extraction.
⮚However, certain precautions should be considered before starting the process of
initial Extraction

18. PRECAUTIONS BEFORE EXTRACTION
I- 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
⮚Certain glycosides are sensitive to alkali and racemize even under mild conditions.
II-Since a glycoside is accompanied in the plant by the special enzyme capable
of hydrolyzing it .
These enzymes must be first deactivated before or during extraction, particularly when Fresh plant
material is used.

19. DEACTIVATION OF ENZYMES MAY BE CARRIED OUT BY:
a-Drying for 15-30 min at 100o C followed by slow drying at a low temperature.
b-Placing the fresh material into boiling water or boiling alcohol for 10-20 min.
c-Boiling with acetone.
d-By carrying out the initial extraction at a very low temperature
e- The fresh material is ground at very low temperature (liquid N2)
f- Freeze drying (lyopholization).

20. ⮚PURIFICATION OF EXTRACTED GLYCOSIDES:
1- ADDITION OF LEAD ACETATE TO PRECIPITATE NON-GLYCOSIDIC CONSTITUENTS E.G. PROTEINS,TANNINS, COLORING
MATTERS AND RESINS
N.B.THIS IS NOT RECOMMENDED IN CASE OF FLAVONOIDS WHICH MAY BE PRECIPITATED.
2-DEFATTING WITH PETROLEUM ETHER IS DESIRABLE IN CASE OF SEEDS.
3- ADDITION OF SOLVENT FOR PRECIPITATION OR CRYSTALLIZATION OF GLYCOSIDES
E.G. ACETONE WITH HYDRO-ALCOHOLIC EXTRACT TO PRECIPITATE SAPONINS.
4- CHROMATOGRAPHIC PURIFICATION BY CC,TLC.

21. Spectrophotometric methods:
▪ By measuring a stable color developed when a specific reagent reacts with a particular compound .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).
▪ By measuring the UV absorption of a compound containing a conjugated diene, where the UV absorption is directly
proportional to the concentration of the compound
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

22. QUALITATIVE IDENTIFICATION
•General test for glycoside
•Specific tests for certain glycoside
Class or Type Chemical tests
Anthraquinone 1. Borntrager’s test
2. Modified Borntrager’s test
Flavone (Flavonoids) Shinoda test
Cyanogenic Giegnard’s test
(Cardiac) 1. Legal’s test
2. Baljet’s test
3. Liberman’s test
Saponins 1. Foam test
2. Haemolytic test
Coumarin U.V. light test

23. Ph.D.Ahmed M.Metwaly
Associate professor,Pharmacognosy
department,
Faculty of Pharmacy,Al-Azhar University.
ametwaly@azhar.edu.eg
Email: ametwaly@azhar.edu.eg 25