Definition: Organic natural compounds present in a lot of plants and some

animals, these compounds upon hydrolysis give one or more sugars (glycone)
and non sugar (aglycone) or called genin.
Glycosides are the compounds formed by the ether linkage or an oxygen
bridge between a sugar and a non-sugar compounds.
Carbohydrate residue is attached by an acetal linkage at carbon atom 1 to a
noncarbohydrate residue or aglycone.
Glycosides are Acetals (Diether products) In which the –OH group of the
sugar is condensed with a hydroxyl group of the nonsugar component and the
secondary hydroxyl group is condensed within the sugar molecule itself to
form an oxide ring.
• As there exist an ether linkage between the sugar and non-sugar component,
glycosides may be considered as sugar ether.
 Glycoside is composed of two parts
a. Sugar part known as glycone Most frequently occurring sugar is β-D-
glucose, although rhamnose, digitoxose, cymarose and other sugars are the
components of glycosides.

b. Non-sugar part known as aglycone Active part of glycoside (which

may be methyl alcohol, glycerol, a sterol, a phenol, etc.)
 Sugar helps in the solubilization of non-sugar, for increasing the
bioavailability of the drug.
 Type of the glycosidic linkage
• Both alpha and beta glycosides are possible, depending on the
stereoconfiguration of the glycosidic linkage.
• a- glycosides
• b- glycosides

• Only beta forms occur in plants, emulsin and most other natural
enzymes hydrolyze only the beta varieties.
 Hydrolysis of glycosides
Glycoside is easily hydrolyzed by an enzyme that occurs in the same
plant tissue
Many of these enzymes hydrolyze only a single glycoside
2 enzymes, namely emulsin of almond kernels and myrosin of black
mustard seeds, each hydrolyze a considerable number of glycosides.
Glycosides that are derivatives of rhamnose require a special
enzyme known as rhamnase for their hydrolysis.
 Naming of glycosides
Generally glycosides are named on the basis of source of glycosides
ending with 'in' such as

strophanthidin from Strophanthus,

digitoxin from Digitalis,
barbaloin from Aloes,
salicin from Salix,
cantharidin from Cantharides, and
prunasin from Prunus.
Systemic name is formed by suffix 'ose' of sugar change to
'oside'
stereochemical anomeric prefix α or β and
configurational prefix (D- or L-) immediately precede the sugar
nomenclature, and the chemical name of the aglycone precedes
the name of the sugar

Amygdalin: D-Mandelonitrile–β-D-glycosido-6-β-D-glucoside
 Function of Glycosides in the plant
1) Source of energy, Energy producers during seedlings
through hydrolysis of stored compounds.
2) Detoxifying agents for many harmful substances
3) Stabilizers of labile substances (transfer insoluble
substances by using sugars) and growth regulators
4) Decorative or attractive substances such as floral
pigments (pollination process)
5) Antibacterial activity and act as Protectives against
microorganisms and insects.
 Glycosidic linkage
• Classification of glycosides on the basis of linkages between the
carbohydrate and non carbohydrate moieties
• If sugar is linkes with non sugar by an ‘oxygen bridge’ Such
glycosides are collectively termed as O-glycosides
O-glycosides found in anthraquinone , cardiac, steroidal and
triterpenic glycosides
If ‘O’ is replaced by ‘S’ it is called S-glycosides; if replaced by ‘N’ is
known as N-glycosides; and if replaced by ‘C’ is termed as C-
glycosides.
C-glycosides found in aloe and cascara
S-glycosides found in black and white mustard
N-glycosides absent in plants, present in nucleosides
• O-Glycosides N-Glycosides

S-Glycosides C-Glycosides

Sinigrin
 Classification on the basis of Glycone
Glucose- Sennoside
Rhamnose- frangulin
Digitoxose-digoxin
Glucose and Rhamnose- Glucorhamnoside-glucofrangulin
Rhamnose and glucose -Rhamnoglucoside-Rutin

Limitation
 Unable to comprise all the glycosides, only a few sugars are known
 Gives no information about the biological activity of the glycoside
 Can’t be concerned about the chemistry of aglycone molecules
 On the basis of therapeutic activity
Such as-
 Cardiac glycoside, eg. Digitalis, strophanthus etc
 Laxative glycosides, eg. Aloe, senna, cascara sagrada
 Local irritant, eg. Sinigrin (Black mustard seeds)
 Analgesics and antipyretics, eg. Salicin (willow or salix bark)
 Anti-inflammatory, Aloin for acne, Glycyrrhizin for peptic ulcer)

Limitation
 Biologically inactive glycosides are out of consideration
 Ignores many chemically important & unique glycosides
 On the basis of the chemical nature of aglycone
Glycosides can be classified into the following groups:
i. Cardioactive/Steroidal: eg. Digitalis, squill, strophanthus
ii. Anthraquinone: eg. aloe, cascara sagrada, rhubarb, senna, aloe
iii. Saponin: eg. Glycyrrhiza, Dioscorea
iv. Cyanophore: eg. Prunasin (wild cherry)
v. Isothiocyanate:eg. Sinigrin
vi. Aldehyde: eg. Vanillin
vii. Lactone: eg. Cantharidine
viii. Bitters: eg. Gentian, Quassia
It involves the two steps:
 Transfer of a uridylyl group from uridine triphosphate (UTP) to a
sugar-1-phosphate forming UDP-sugar & inorganic pyrophosphate.
Enzyme catalyzing this reaction are referred to as uridylyl
transferases.
 Transfer of the sugar from UDP to a suitable acceptor (aglycone),
mediated by enzyme glycosyl transferases, thus forming the
glycoside.
 Biosynthesis Pathway of Prunasin (Cyanophore glycoside)
 The amino acid phenylalanine is the precursor. An aldoxime, a nitrile and a
cyanohydrin are involved as intermediates in the pathway
 The presence of a chiral center in the mandelonitrile provides the
opportunity for 2 β-glucosides to occur.
 Prunasin (D-mandelonitrile glucoside)
 Prunasin is formed in wild cherry by transfer of the
sugar from UDP to an aglycone
 Extraction of Glycosides
Wide range of the constituents associated with glycosides so there is
no common mthod is recommended
Water, methanol, ethanol are the most common solvents for the
extraction of glycosides.
1)Deactivation of enzymes
●Drying for 15-30 min at 100 oC followed by slow drying at a low
temperature.
●Dipping the fresh material into boiling water or boiling alcohol for 10-
20 min.
●Boiling the fresh plant material with acetone.
●Carrying out the extraction at very low temp.
●Freeze-drying of the plant material before extraction (lyophilization).
 2- Maintenance of neutral conditions by using (NH2)SO4
Neutral pH should be assured before and during extraction because:
• Acidity may result in hydrolysis. This is overcome by addition of
CaCO3.
• Mild alkalinity may sometimes produce racemization.

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

High amounts of lipids hinder the glycoside extraction.
Defatting is usually carried with petroleum ether
 4- Purification of extracted glycosides
 Addition of lead acetate solution to the extract to precipitate
the non-glycosidic constituents.
 This is not recommended in case of flavonoid glycosides which
may be precipitated
 Addition of solvent for precipitation or crystallization of
glycosides e.g. by dissolving the extract in hydroalcoholic or
alcoholic solution and then adding acetone or ether to
precipitate or crystallize out the glycosides.
 Chromatographic techniques such as CC or TLC are commonly
used for purification
 Anthraquinone Glycosides
• A number of glycosides with aglycones related to anthracene
• Anthracene glycosides are abundantly found in various dicot plant
families, such as: Ericaceae, Euphorbiaceae, Leguminoseae,
Polygonaceae, Rhamnaceae, Rubiaceae
• Some monocots belonging to the family Liliaceae
• Certain varieties of fungi and lichens
• Noticeable amount is present in drugs as cascara sagrada,
frangula, aloe, rhubarb, senna
• With the exception of chrysarobin (which is too irritating), these
drugs are employed as Cathartics
 Biosynthesis of anthracene aglycones
It has been established from a study with microorganisms
An intermediate poly b-ketomethylene acid is formed
from 8 acetate units and by intramolecular condensation gives rise
to anthraquinones (emodin and other related derivatives)
 Anthranols and anthrones are intermediates in the formation of
anthraquinones

Poly— Ketomethylene Acid emodin and other related derivatives

Another metabolic pathway for the formation of anthraquinone
It is recognised through the shikimic acid—mevalonic acid
mediators as could be functional in certain plants belonging to
the family Rubiaceae

The transglycosylation reaction creates a glycoside at a late stage

in the pathway
Aloe is the dried juice of the leaves of various species of Aloe.
 Aloe perryi (Socotrine aloes)
 Aloe barbadensis (Curacao aloes) and
 Aloe ferox (Cape aloes).
Liliaceae family

Aloe perryi Aloe barbadensis Aloe ferox

 Chemical constituents
Aloe contain a number of anthraquinone glycosides.
Principal one is Aloe-emodin occurs in the free state and as a
glycosides in various species of Aloe and also in Rhubarb

 Barbaloin is Aloe-emodin anthrone C-10 glucoside

 Emodin: Structural Relationships of its Derivatives
• The glycosides of anthranols, dianthrones, and oxanthrones i.e., the
reduced derivatives of anthraquinones, invariably found in various
plant substances.
• These plant products do make an appreciable contribution to the
inherent therapeutic values of the naturally occurring substances.
 Anthraquinone
derivatives
Anthrones and anthranols
are reduced anthraquinone
derivatives

They occur either as free

or combined as glycosides.

Anthrones are converted

on oxidation into their
corresponding
anthraquinones,
oxanthrone and dianthrone
 Uses
1. Aloes and aloin are used as a purgative by exerting its action
mainly on colon
2. Aloes as an external aid to painful inflammatory manifestations.
3. It constitutes an important ingredient in the ‘Compound Tincture
of Benzoin’
4. Aloe gel made from the mucilaginous latex of A. vera is frequently
employed in the treatment and cure of radiation burns to get
immediate relief from itchings and pains.
 Rhubarb
Rhubarb is the rhizome and roots of Rheum officinale , belonging
to the family Polygonaceae
Chemical Constituents Rhubarb contains mainly the
anthraquinone glycosides and are broadly classified into four
categories
Anthraquinones with —COOH moiety—e.g., Rhein

Anthraquinones without —COOH moiety —e.g.,Emodin; Aloe-

Emodin; Chrysophanol
 Anthrones and Dianthrones of Emodin

Heterodianthrones
Palmidin A, B, and C, produced from two different anthrone
molecules
Palmidin A : Aloe-emodin anthrone + Emodin anthrone
Palmidin B : Aloe-emodin anthrone + Chrysophanol anthrone
Palmidin C : Emodin anthrone + Chrysophanol anthrone
Astringet action of rhubarb chiefly due to the components namely: gallic
acid as α- and β-glucogallin; tannin as d-catechin and epicatechin
 Rhubarb' s constituents are rheinolic acid, pectin, starch, fat
and calcium oxalate.
Uses
• It is used mainly in the form of an ointment in the treatment and
cure of chronic eczema, psoriasis and trichophytosis—as a potent
keratolytic agent.
• It is employed in the treatment of diarrhoea.
• It is also used as a purgative.