GLYCOSIDES

1
GLYCOSIDES
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

5
(No Transcript)
6
(No Transcript)
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.

9
(No Transcript)
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.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 .

16
(No Transcript)
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.

18
(No Transcript)
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

• 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

• 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 10-20 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. 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. 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.