GlycosidesGlycosides

IntroductionIntroduction

Definition:Definition: Glycosides are non-reducing organic Glycosides are non-reducing organic compounds that on hydrolysis with compounds that on hydrolysis with acids, alkalis or enzymes yield:acids, alkalis or enzymes yield:

A sugar part (or glycone, formed of one A sugar part (or glycone, formed of one or more sugar units).or more sugar units).

A non-sugar part (or aglycone, also A non-sugar part (or aglycone, also called genin).called genin).

Classification:Classification: Atom from the aglycone involved in the Atom from the aglycone involved in the

glycosidic linkage:glycosidic linkage: Aglycone- O- Sugar O-glycosidesAglycone- O- Sugar O-glycosides Aglycone- C- Sugar C-glycosidesAglycone- C- Sugar C-glycosides Aglycone- S- Sugar S-glycosidesAglycone- S- Sugar S-glycosides Aglycone- N- Sugar N-glycosidesAglycone- N- Sugar N-glycosides

Number of sugars:Number of sugars: One sugarOne sugar monosidesmonosides e.g. Salicin.e.g. Salicin. Two sugarTwo sugar BiosidesBiosides e.g. Diosmin.e.g. Diosmin. Three sugars TriosidesThree sugars Triosides e.g. Digoxin.e.g. Digoxin.

Nature of the glycoside:Nature of the glycoside: Primary glycosides: Originally present in the plant Primary glycosides: Originally present in the plant e.g. e.g.

Purpurea APurpurea A Secondary glycosides: Resulted from removal of one sugar Secondary glycosides: Resulted from removal of one sugar

from the primary glycosides from the primary glycosides e.g. e.g. DigitoxinDigitoxin

Type of the glycosidic linkage:Type of the glycosidic linkage: - glycosides- glycosides - glycosides- glycosides

Botanical source:Botanical source: Digitalis glycosidesDigitalis glycosides Senna glycosides.Senna glycosides.

Therapeutic use:Therapeutic use: Analgesic glycosides.Analgesic glycosides. Purgative glycosides.Purgative glycosides. Cardiac glycosides.Cardiac glycosides.

Chemical nature of the aglycone:Chemical nature of the aglycone: Flavone glycosides.Flavone glycosides. Steroidal glycosides.Steroidal glycosides. Aldehydic glycosides.Aldehydic glycosides.

Physical Characters:Physical Characters:

Solids either amorphous or Solids either amorphous or crystalline.crystalline.

Non volatile.Non volatile. Usually bitter in taste.Usually bitter in taste. Soluble in water and polar organic Soluble in water and polar organic

solvents.solvents. Reduce Fehling’s solutions only after Reduce Fehling’s solutions only after

hydrolysis.hydrolysis.

Stability of Glycosides:Stability of Glycosides:

1- Effect of acid hydrolysis:1- Effect of acid hydrolysis: Acids split sugars from the aglycones.Acids split sugars from the aglycones. The acetal linkage is more readily cleaved The acetal linkage is more readily cleaved

than the linkage between the individual than the linkage between the individual sugars of the sugar chain.sugars of the sugar chain.

C-glycosides are resistant to acid C-glycosides are resistant to acid hydrolysis.hydrolysis.

2- Effect of alkaline hydrolysis:2- Effect of alkaline hydrolysis:A- Strong alkalis:A- Strong alkalis:

Hydrolysis of ester groups.Hydrolysis of ester groups. Opening of lactone rings e.g. Cardiac Opening of lactone rings e.g. Cardiac

glycosides.glycosides.

B- Mild alkalis:B- Mild alkalis: Hydrolysis of ester groups Hydrolysis of ester groups e.g. Lanatoside A e.g. Lanatoside A

to Purpurea Ato Purpurea A Opening of lactone rings e.g. Cardiac Opening of lactone rings e.g. Cardiac

glycosides.glycosides.

3- Enzymatic hydrolysis:3- Enzymatic hydrolysis:

Split the sugars stepwise starting from the Split the sugars stepwise starting from the terminal sugars.terminal sugars.

All plants producing glycosides have enzyme All plants producing glycosides have enzyme that can hydrolyze these glycosides.that can hydrolyze these glycosides.

Enzymes are specific for the type of Enzymes are specific for the type of glycosidic linkages:glycosidic linkages:

Emulsin can hydrolyze Emulsin can hydrolyze - glycosides- glycosides Invertase can hydrolyze Invertase can hydrolyze - glycosides- glycosides Myrosin can hydrolyze s-glycosides.Myrosin can hydrolyze s-glycosides.

Extraction and IsolationExtraction and Isolation Because of the wide range of physical and chemical Because of the wide range of physical and chemical

properties of glycosides and other constituents properties of glycosides and other constituents associated with them, no common general method associated with them, no common general method for their isolation is recommended. for their isolation is recommended.

Water, methanol, water-ethanol and ethanol are the Water, methanol, water-ethanol and ethanol are the most common solvents for extraction of glycosides.most common solvents for extraction of glycosides.

Precautions before extractionPrecautions before extraction Deactivation of enzymes:Deactivation of enzymes:

DryingDrying for 15-30 min at for 15-30 min at 100 oC100 oC followed by slow drying followed by slow drying at a low temperature.at a low temperature.

Dipping the fresh material into Dipping the fresh material into boiling waterboiling water or or boiling boiling alcoholalcohol for 10-20 min. for 10-20 min.

Boiling Boiling the fresh plant material with the fresh plant material with acetoneacetone.. Carrying out the extraction at very low temp.Carrying out the extraction at very low temp. Freeze-dryingFreeze-drying of the plant material of the plant material before extractionbefore extraction

(lyophilization).(lyophilization). Carrying the extraction in the presence of (NHCarrying the extraction in the presence of (NH44))22SOSO44..

Maintenance of neutral conditions:Maintenance of neutral conditions: Neutral pH should be assured before and Neutral pH should be assured before and

during extraction because:during extraction because: Acidity may result in hydrolysis. This is Acidity may result in hydrolysis. This is

overcome by addition of CaCO3. overcome by addition of CaCO3. Mild alkalinity may sometimes produce Mild alkalinity may sometimes produce

racemization.racemization.

Defatting of fat-rich organs (e.g. Defatting of fat-rich organs (e.g. seeds) before extraction:seeds) before extraction:

High amounts of lipoids hinder glycoside High amounts of lipoids hinder glycoside extraction. Defatting is usually carried with extraction. Defatting is usually carried with petroleum etherpetroleum ether

Alcoholic and Phenolic Alcoholic and Phenolic GlycosidesGlycosides

1- Salicin1- Salicin Source: Source: Salix species (Willow bark).Salix species (Willow bark). Nature: Nature: Primary achholic and Phenolic Primary achholic and Phenolic

glycoside (monoside).glycoside (monoside). Uses: Uses: Analgesic- Antipyretic- Anti-Analgesic- Antipyretic- Anti-

inflammatory.inflammatory.

CH2OH

O-glc

Enzyme

CH2OH

OHSaligenin

(Salicyl alch.)

+Glucose

AcidO

CH2OH

HOH2C

+Glucose

Saliretin

OH

O-glc

OCH3

O-glc

OH

OH

+ GlucoseHydrolysis

Hydroquinone

ArbutinMethylarbutin

2- Arbutin & Methyl 2- Arbutin & Methyl ArbutinArbutin

Source: Source: Uva Ursi (Bearberry leaves).Uva Ursi (Bearberry leaves). Nature: Nature: Primary Phenolic glycoside Primary Phenolic glycoside

(monoside).(monoside). Uses: Uses: Diuretic- Bactericidal.Diuretic- Bactericidal.

Aldehydic GlycosidesAldehydic Glycosides1- Glucovanillin1- Glucovanillin

Source: Source: Vanilla pods.Vanilla pods. Uses: Uses: Flavouring agent- Spray reagent.Flavouring agent- Spray reagent.

CHO

O-glc

OCH3

CHO

OH

OCH3

Enzymatic Hydrolysis

Vanillin

Green vanilla podsBitter in taste

Odourless

Brown vanilla podsSweet in tasteVanilla odour

+ Glucose

Glucovanillin

Commercial Preparation of Commercial Preparation of VanillinVanillin

CH2-CH=CH2

OH

OCH3

CH=CH-CH3

OH

OCH3

OH

OCH3

CH=CH-CH2OH

O-glc

OCH3

Eugenol

KOH

Iso-eugenol

OxidationVanillin

VanillinCHCl3+ NaOH

Reflux

Guaiacol

VanillinH2SO4/K2Cr2O7Coniferin

Cyanogenic GlycosidesCyanogenic Glycosides Cyanogenic glycosidesCyanogenic glycosides (Cyanogentic or (Cyanogentic or

Cyanophore Glycosides) are Cyanophore Glycosides) are O-glycosidesO-glycosides yielding yielding HCN gas on hydrolysisHCN gas on hydrolysis . .

They are condensation products of HCN to a They are condensation products of HCN to a carbonyl compounds (Cyanohydrin).carbonyl compounds (Cyanohydrin).

C

R

R

O C

R

R OH

CN

HCNC

R

R O-Sug

CNGlycosylation

Unstable Stable

1- Amygdalin1- Amygdalin Source: Source: Bitter Almond.Bitter Almond. Structures: It is a Structures: It is a Bioside of Bioside of

mandilonitril.mandilonitril.

CH

CN

O glc glc

CH

CN

O glc

Amygdalin Prunasin

1-6 linkage

CH

CN

O H

Mandilonitril

CHOHCN +

Amygdalase Prunase

2- Linamarin2- Linamarin Source: Source: Linseed.Linseed. Structures: Structures: It is the glycosidic derivative of It is the glycosidic derivative of

the cyanohydrin of acetone.the cyanohydrin of acetone.

Uses:Uses: Linamarin has a molluscecidal activity.Linamarin has a molluscecidal activity. Amygdalin is used for the preparation of Amygdalin is used for the preparation of

Benzaldehyde.Benzaldehyde. Cyanogenic glycosides have role in cancer Cyanogenic glycosides have role in cancer

treatment.treatment.

C

H3C

CNH3C

O glc

Test for Cyanogenic Glycosides:Test for Cyanogenic Glycosides:

Reduce plant material to small pieces and Reduce plant material to small pieces and moisten with water.moisten with water.

Incubate at temp. less than 45 Incubate at temp. less than 45 00C for 30 60 mins C for 30 60 mins with the neck of the flask stoppered and have with the neck of the flask stoppered and have suspended sodium picrate paper.suspended sodium picrate paper.

The paper will turns brick red due to the release The paper will turns brick red due to the release of HCN gas.of HCN gas.

ThioglycosideThioglycosideGlucosinolates- Sulphur Glucosinolates- Sulphur

GlycosidesGlycosides They are S-glycosides widely distributed in family They are S-glycosides widely distributed in family

Cruciferae.Cruciferae. Sinigrin: Sinigrin: In seeds of In seeds of Brassica nigra Brassica nigra (black (black

mustard).mustard). Sinalbin: Sinalbin: In Seeds of In Seeds of Brassica alba Brassica alba (white (white

mustard).mustard).

Uses:Uses: Rubefacients, Counter irritants and Rubefacients, Counter irritants and condiment.condiment.

H2CHC C

H2

C

N-O-SO3K

S-Glc

Sinigrin

GarlicGarlic It consists of the bulb of It consists of the bulb of Allium sativumAllium sativum Fam. Fam.

Liliaceae.Liliaceae. The intact cells of garlic contain an odorless, The intact cells of garlic contain an odorless,

sulfur-containing amino acid derivative (+)-sulfur-containing amino acid derivative (+)-SS--allyl-allyl-LL-cysteine sulfoxide, commonly known as -cysteine sulfoxide, commonly known as alliin. alliin.

Alliin is hydrolyzed by the effect of alliinase Alliin is hydrolyzed by the effect of alliinase enzyme present in different cells after crushing enzyme present in different cells after crushing into allicin (diallyl thiosulfinate).into allicin (diallyl thiosulfinate).

Allicin is responsible for the characteristic Allicin is responsible for the characteristic odor and flavor of garlic.odor and flavor of garlic.

Allicin is a potent antibacterial, Allicin is a potent antibacterial, antihyperlipidemic, and it inhibits platelet antihyperlipidemic, and it inhibits platelet aggregation and enhances the blood aggregation and enhances the blood fibrinolytic activity.fibrinolytic activity.

SH

O

NH2

COOHS

S

O

Alliinase + H2O

Alliin Allicin