GlycosidesIntroduction & Classification

By

Dr. Mukul TailangProfessor

School of Studies in Pharmaceutical Sciences

Jiwaji University

Gwalior (M.P.)

GLYCOSIDESGlycosides are the molecules in which a sugar

part is bound to some other non-sugar part. Glycosides play numerous important roles in

living organisms. 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.

GLYCOSIDESFormally, a glycoside is any molecule in

which a sugar group is bonded through its anomeric carbon to another group via a glycosidic bond.

The sugar group is known as the Glyconeand the non-sugar group as the Aglyconeor Genin part of the glycoside.

The glycone can consist of : ◦ Single sugar group (Monosaccharide) or

◦ Several sugar groups (Oligosaccharide).

Glycosidal Sugars:Sugars found in glycosides may be

• Monosaccharides

–Glucose

–Rhamnose

– Fructose

• Deoxysugars (more rare)

–Cymarose

• found in the cardiac glycosides

TERMS USED TO DESCRIBE GLYCOSIDES

A Glycoside is a

• Glucoside –Has glucose as the sugar component

• Pentoside –Has a sugar such as arabinose

• Rhamnosides–Contains rhamnose

• Rhanmoglucosides–Contains both rhamnose and glucose

Glycosidic bond

• A glycosidic bond is a certain type of a functional group that joins alcoholic group of a Carbohydrate molecule to an aglycone molecule.

• A substance containing a glycosidic bond is a Glycoside.

Glycosidic bond

Classification of GlycosidesGlycosides can be classified by :

• The nature of Glycone

• Number of sugars

• Nature of the glycoside

• Botanical source

• Therapeutic use

• The type of Glycosidic Bond

• The Glycosidal Linkage and

• Chemical nature of Aglycone.

By Glycones• 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.

Number of sugars:• One sugar monosides e.g. Salicin.

• Two sugar Biosides e.g. Diosmin.

• Three sugars Triosides e.g. Digoxin.

Nature of the glycoside:• Primary glycosides: Originally present in the

plant

–e.g. Purpurea A

• Secondary glycosides: Resulted from removal of one sugar from the primary glycosides

–e.g. Digitoxin

•Botanical source:•Digitalis glycosides

•Senna glycosides.

•Therapeutic use:•Analgesic glycosides.

•Purgative glycosides.

•Cardiac glycosides.

Classifications of glycosides according to their therapeutic effects

CHF and cardiac muscles stimulators: • Digitalis glycosides: digoxin, digitoxin,

gitoxin (Fox glove leaves)

• Ouabain: Strophanthus gratus seeds

• K-strophanthin -Strophanthus kombe seeds

• Scillaren A,B which isolated from red and white Squill bulbs

• Convolloside: Convallaria majalis – Lily of the Valley.

Laxative group of glycosides:

– Sennoside A,B,C,D (Senna leaves and fruits)

– Cascaroside A,B (Cascara bark)

– Frangulin and glucofrangulin (Frangula bark)

– Aloin and barbaloin (Aloe vera and A. barbadensis)

Local irritant group:

– Sinigrin (Black mustered seeds_Brassica nigra)

– Sinalbin (White mustered seeds_Brasica alba)

Analgesics and antipyretics:

– Salicin Salisylic acid (Willow or Salix bark)

Keeping elasticity of blood vessels like:

– Rutin, Rutoside (Bitter orange peels, Lemon peels)

Anti-inflammatory group:

– Aloin for acne &

– Glycyrrhizinin the treatment of peptic ulcer

hydrolysis

By type of glycosidic bondDepending on whether the glycosidic bond lies "above" or "below" the plane of the cyclic sugar molecule, glycosides are classified as:

»α-glycosides

»β-glycosides

α- & β-glycosides

OH

H OH

OH H

H OH

H

H

O

O CH3

OH

H OH

OH H

H OH

H

O

HH3CO

O

CH2OH

H

H

OH

OH

HH

OH HO CH

3

O

CH2OH

H

H

OH

OH

H

OH HH

O CH3

methyl glucoside methyl glucoside

methyl glucoside methyl glucoside

By Linkage

- O - C6H

11O

5- O - H H - O - C6H

11O

5+O - Glycoside

C - H C - C6H

11O

5H - O - C

6H

11O

5+C - Glycoside

N - H N - C6H

11O

5H - O - C

6H

11O

5+N - Glycoside

- S - H - S - C6H

11O

5H - O - C6H

11O

5+S - Glycoside

Atom from the aglycone involved in the glycosidic linkage:

Aglycone- O- Sugar O-glycosides

Aglycone- C- Sugar C-glycosides

Aglycone- S- Sugar S-glycosides

Aglycone- N- Sugar N-glycosides

O,C,S & N – GLYCOSIDES

CH2 = CH - CH

2 - C = N - O - SO

3K

S - Glucose

OO OH

R1

R2

OHO O

C6H

11O

5.

C6H

11O

5.

OH OH

CH2OH

O

O

CH2OH

H

H

OH

OH

H

OH HH

O

H

H

OH

H

OH

H

OH

N

N

N

N

NH2

Sinigrin

10

10'

Barbaloin

(S - Glycoside)

Sennoside

(O - Glycoside)(C - Glycoside)

Adenosine

(N - Glycoside)

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.

»Anthraquinone glycosides

»Simple phenolic glycoside

»Thioglycosides

»Flavonoid glycosides

»Steroidal glycosides or cardiac glycosides.

»Saponins

»Coumarin glycosides

»Cyanogenic glycosides

Anthraquinone glycosidesO

O

OH

O

H H

O

H OH

O

O

OH OH

O

O

OH OH

CH3

OH

O

O

OH OH

CH2OH

O

O

OH

OH

OOH OH

CH3

OH

O

CH3

OH

OH OH

OOH OH

O

CH3

OH OH

OH OHO

O

COOH

O

O

OH OH

CH3

OH

A B C

(I) Anthraquinone (II) Anthranol

(III) Anthrone (IV) Oxyanthrone Fizacine

Emodine Aloe emodine Alizarine

EmodindianthronRizofanoldianthron

Rhein

Frangula emodine

Simple phenolic glycosideO OMe

O CH2CH

2 OHO

CH2OH

O

OH

COOH

OO

CH2OH

H

H

OH

OH

H

OH HH

O

CH2OH

H

H

OH

OH

H

OH HH

O

CH2OH

H

H

OH

OH

H

OH HH

O

CH2OH

H

H

OH

OH

H

OH HH

O

CH2OH

H

H

OH

OH

H

OH HH

Methyl arbutin

SalidrozineSalicine

Glycoside of Salysilic acid

Arbutin

Thioglycosides

CH2 = CH - CH

2 - C = N - O - SO

3K

S - Glucose

O

MeO

MeO

O5H

11C

6 - S : N - H

2C CH : CH . CO

OCH2.CH

2.N(CH

3)3.H

2SO

4

Sinigrin

+

Sinalbin

Flavonoid glycosidesO

O

O

O

O

OH

O

O

OH

O

O

O

O

O

OH

OH

OHOH

R

R'

O

OH

O

O

O

CH

O

O

OH

OH

Glucose - O

Rhamnose

O

OH

OH

O

O - Glucose - Rhamnose

OH

OH

O

OH

OH

OHOH

OH

H

Flavone

Flavan

Flavanol

Flavanone Flavanonol

+

Anthocyanidine

Chalcone

Catechine

Aurones

Pelargonidine - R=H, R'=H

Cynadine - R=OH, R'=H

Naringin

Rutin

+

Cynadine

Steroidal glycosides or cardiac glycosides

CH3

OH

OHH

H

H

H

OH

OH

O O

HO

O

O O

CH3

OH

OHH

H

H

HOH

O O

CH3

OH

OHH

H

H

HO-C-H

O O

O

CH3

OH

OHH

H

H

H

O O

Digitoxigenin

C

Strophanthidin

H-C-H

OH

OH

OH

HO

Gellebrigenol

Gitoxigenin

Gitaloxigenin

Digitoxigenin

Saponins

OH

O

O

OH

O

O

O

OHOH

OH

O

DiosgeninHecogenin

-amyrin -amyrin

Lupeol

Damaran

Coumarin glycosides

O O

Coumarin

Cyanogenic glycosides

O

CH2OH

H

H

OH

H

H

OH H

O

CH2

H

H

OH

OH

H

OH H

CH(CN)

C

CH3

O-C6H

11O

5

CNCH3

O

O

Amygdalin

Linamarin