1. GLYCOSIDES
By : - Jaspreet Rekhi

2. is an organic compound, usually of plant origin, that is composed of a sugar portion linked to a non-sugar moiety. The sugar portion is called glycone, while the non-sugar portion is called aglycone or genin .
A glycoside

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

4. The linkage between the sugar and the aglycone is an acetal linkage.
Types of Glycosides :
I- According to atoms involved in the glycosidic linkage:
1- O-glycosides
2- C-glycosides
3- S-glycosides
4- N-glycosides

7. II- According to the configuration of the glycosidic linkage:
1- -glycosides:
Here the sugar involved has the  configuration at the hemiacetal carbon.
The majority of plant glycosides isolated are -glycosides.

8. 2-  -glycosides :
Here the sugar involved has the  configuration at the hemiacetal carbon; the sugar is usually of the L-series e.g. L-rhamnose. There are only few medicinal -glycosides known, especially the rhamnosides.

10. III- According to the sugar moiety:
1-Glucosides:
2- Ribosides:
3- Rhamnosides:
IV- According to the aglycone:
1-Cardiac glycosides
2- Flavonoid glycosides
3- Anthracene glycosides

11. 4- Saponin glycosides
5-Thioglycosides
6- Cyanogenic glycosides
7- Phenolic glycosides possessing phenolic aglycones e.g. arbutin.
8- Alcohol glycosides, with alcoholic aglycones e.g. salicin.
9-Antibiotic glycosides
e.g, Amino-glycoside antibiotics

12. 10- Ester glycosides, such as the glycosides of methyl salicylate e
10- Ester glycosides, such as the glycosides of methyl salicylate e.g gaultherin
11- Aldehyde glycosides, with an aldehyde aglycone e.g. glucovanillin .
12- Terpene glycosides :
a- Monoterpene glycosides e.g. gentiopicrin and loganin.
b- Triterpene saponin glycoside.

13. 13- Glycoalkaloids:
These are the glycosidal alkaloids i.e. They possess a glycosidic
linkage and a cyclic nitrogen in the aglycone. e.g steroidal alkaloids of Solanum species e.g.
solanine.

14. 14- Complex glycosides:
These include a number of complex secondary carbohydrates e.g. gums, mucilage & pectin; a number of glycosidal resins e.g. Jalap resin as well as a number of glycosidal tannins e.g. glucogallin in Rhubarb.

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

17. 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, so we are dealing with a diglycoside e.g.

19. The sugars involved:
1- b-D-glucose is the most common sugar in glycosides.
2- Other sugars include :
i - Other hexoses e.g. galactose
ii - Pentoses e.g. ribose, xylose and arabinose.
iii - 6-Deoxyhexoses e.g. rhamnose and digitalose.

20. The 6-Deoxy sugars and 2,6-Dideoxy sugar are common in
iv - 2,6-Dideoxysugars e.g. sarmentose, digitoxose and cymarose (rare sugars)
The 6-Deoxy sugars and 2,6-Dideoxy sugar are common in
Cardiac glycosides.

21. vi - A uronic acid e.g. glucuronic acid found in glycyrrhizin .

22. Effect of the sugar portion on solubility of the glycoside:
Ex. 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 .

23. 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 sugars . Thus milder conditions can be chosen to hydrolyze the glycoside involving 2-deoxysugars, without affecting the others .

24. 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.

25. 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.

26. 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

27. 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.

28. 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.

29. 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.

30. - 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 .

31. enzymes that may be present in the same plant.
N.B
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.

32. 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.

33. 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.

34. Extraction and Isolation
1- Acidic conditions should be avoided during extraction.
2- Inactivation of the enzymes:
a- Boiling alcohol for minutes.
b- Boiling with acetone.
c- Low temperature i.e. in the cold.
d- precipitates the enzymes with ammonium sulfate.

35. 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.

36. After filteration, the alcoholic extract is concentrated, and the glycosides may crystallize…
( oily seeds should be defatted).

37. Pharmacological or Therapeutic Activity :
1- cardiac glycosides of Digitalis, Strophanthus, and squill are cardiotonic agents useful in congestive heart failure.
2- Anthracene glycosides of cascara, Frangula, senna, Rhuharb, Aloes have a laxative effect.

38. 3- Flavonoid glycosides e. g
3- Flavonoid glycosides e.g. rutin and hesperidin are used to decrease capillary fragility and permeability.
4- In case of cyanogenic or thioglycosides, that the aglycone is the active component used. The aglycone from the former (e.g. HCN & Benzaldehyde) is useful as a sedative and flavoring agent

39. aglycone from the latter (e. g
aglycone from the latter (e.g. allyliso- thiocyanate) is useful as a rubifacient and counterirritant.
Generally the pharmacological action of the glycoside is due to the aglycone. However, the sugar portion is necessary to carry the aglycone to the site of action.

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By : - Jaspreet Rekhi