Glycosides

Definition
• Organic natural compounds present in a lot of
plants and some animals, these compounds
upon hydrolysis give one or more sugars
(glycone) β_form 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.

• Glycoside is composed of two parts-
a. Sugar part known as glycone
The 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
It is the active part of glycoside.
Sugar helps in the solubilization of non-sugar, for
increasing the bioavailability of the drug.

O
C H 2 O H
O H
O H
O H
O R
H H 2 O
O
C H 2 O H
O H
O H
O H
O H
R O H
S u g a r N o n - S u g a r

• Solubility:
glycosides are water soluble compounds and
insoluble in the organic solvents.
Glycone part: water soluble, insoluble in the
organic solvents.
Aglycone part: water insoluble, soluble in the
organic solvents.
Some glycosides soluble in alcohol.

Chemically Glycosides are Acetals
- In which the –OH group of the sugar is
condensed with a hydroxyl group of the non-
sugar 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.

R C H
O
R' OH R C
H
OR'
OH
R C
H
OR'
OR"
R"OH
Hemiacetals Acetals
O
CH2OH
OH
OH
OH
OR
O
CH2OH
OH
OH
OH
OH
ROH
Sugar Non-Sugar

• The sugar can be linked through S, N, C.
• In case of S-linkage it is thioether, but the
glycosides condensed by N & C atom are not
ether sugar, simply glycosides.
• So all glycosides are not ether sugar.
• For example: Adenoside (N-link), Sinigrin (S-
link), Barbaloin (C-link)

Classification of Glycosides
A. On the basis of sugar moiety
Such as-Glucoside, rhamnoside,
digitoxoside, xyloside, arabinoside etc.
C H 2O H
O C 6H 11O 5
S alicin
Saligenin G lucose
O
O H
C 6 H 1 1 O 5
A r b u t i n
H y d r o q u i n o n e G l u c o s e

Limitation
1. It is unable to comprise all the glycosides,
only a few sugars are known
2. Gives no information about the biological
activity of the glycoside
3. One can’t be concerned about the chemistry
of aglycone molecules here

B. On the basis of therapeutic activity. Such as-
-Cardiac glycoside, eg. Digitalis,
strophanthus etc
-Laxative glycosides, eg. Aloe, senna,
cascara sagrada

Limitation
1. Biologically inactive glycosides are out of
consideration
2. Ignores many chemically important & unique
glycosides

C. On the basis of linkage of sugar molecule with
the aglycone
i. O-glycosides: Here the sugar is combined
with the alcoholic or phenolic hydroxyl group
of the aglycone.
R=glucose in daucosterol R= rhamnose
RO
Sitosterol
O
OH
OCH3
OH
RO
O
Diosmin

ii. N-glycosides: In this
glycosides the nitrogen or
amino group (-NH2/-NH-) is
condensed with sugar. Eg.
Neucleosides, Co-enzymes
etc.
N
N
N
N
N H 2
O
C H 2 O H
O H O H
A d e n o s i n ( C o - e n z y m e A )
( A d e n i n e + R i b o s e )

iii. S-glycosides: These glycosides contain a sugar
moiety attached to a sulphur of the aglycone.
Eg. Isothiocyanate glycosides.
C 3 H 5 C S
N
C 6 H 1 1 O 5
O S O 3 K
S i n ig r in

iv. C-glycosides: Condensation of a sugar directly
to a carbon atom of aglycone gives C-glycoside.
Eg. Cascarosides, aloin etc.
H C 6 H 1 1 O 5
O HO H O
C H 2 R
R = - O H , B a r b a l o i n
R = - H , C h r y s a l o i n
R = - C 6 H 1 1 O 5 , C a s c a r o s i d e s A / B

Limitation
1. Biological activities are ignored here.
2. Number of aglycones are ignored.
3. Linkage of sugar molecules with aglycones
never indicate the pharmaceutical activities
of the glycosides.

D. On the basis of the chemical nature of
aglycone the glycosides can be classified into the
following groups:
i. Cardioactive/Steroidal: eg. Digitalis, squill,
strophanthus
O
OH
HO
O
Digitoxigenin
+Digitoxose Digitalis
Cardenolide, C23 Steroid

ii. Anthraquinone: Eg. aloe, cascara sagrada,
rhubarb, senna, barbaloin
H C 6 H 1 1 O 5
O HO H O
C H 2 R
R = - O H , B a r b a l o i n
R = - C 6 H 1 1 O 5 , C a s c a r o s i d e s A / B

iii. Saponin:
O
O
H O
G lycyrrhiza
D ioscorea
+ rham + glu
D iosgenin

iv. Cyanophore: eg. Prunasin
v. Isothiocyanate:
C O
H
CN
C6H11O5
Mandelonitrileglucoside
Wildcherry
Bitteralmond
C3H5CS
NOSO3K
C6H11O5
Sinigrin
Blackmustard
Whitemustard

vi. Flavonol/Flavonoid:
O
O
O H
O H
H O
O H
O C 1 2 H 2 1 O 9
R u tin
C itru s

vii. Alcohol:
viii. Aldehyde:
CH2OH
OC6H11O5
Salicin(Saligenin+Glucose)
Salixpurpurea
S.fragilis
CHO
OCH3
OR
Vanillaplanifolia
V.tehitensis
R=H,Vanillin
R=glu,glucovanillin

ix. Lactone:
x. Phenol:
O O
Coumarin
Cantharides
Tonkabeans
O
OH
C6H11O5
Arbutin
Uva ursi

xi. Tanin:
HO
OH
OH
COO C6H11O5
Glucogallin
Nutgall
Hamamelis leaf

Biosynthesis of Glycosides
• It involves the following two steps:
1. 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.
UTP+Sugar-1-PO4
Uridylyl
transferase
UDP-sugar+PPi

2. Transfer of the sugar from UDP to a suitable
acceptor (aglycone), mediated by enzyme
glycosyl transferases, thus forming the glycoside.
UDP-sugar+Acceptor(aglycone) Acceptor-sugar(glycoside)+ UDP
glycosyl
transferase

Biosynthesis Pathway of Prunasin
(Cyanophore glycoside):
 The amino acid phenylalanine is the starting 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) is formed in wild cherry
(Prunus serotina). The isomeric sambugrin (L-mandelonitrile
glucoside) is formed in Sambucus nigra.
 These compounds don’t occur in the same species.

H
H
H
COOH
NH2
H
H
H
COOH
NHOH
H
CH
H
NOH
OH
C
H
N
O
C
H
N
Glucosyl transferase
C6H11O5
L-Phenylalanine N-hydroxy-L-phenylalanine
Phenylacetaldoxime
H
C
H
N
Mandelonitrile
 -hydroxy mandelonitrile
Prunasin
+ UDP-glucose

Functions of glycosides:
• In plant- glycosides play an important role in the
life of plant & are involved in its
1. Regulatory function
2. Protective function
3. Sanitary function
• In animal- Because of their wide varieties of
chemical nature of glycosides, their
pharmacological actions are also widely
distributed
1. Cardioactive- Digitalis, squill, strophanthus
2. Laxative- emodin (From Senna, Aloe, Cascara sagrada, Rhubarb)
3. Analgesic- Methyl salicylate (From wintergreen oil)
4. Local irritant- Allyl isothiocyanate (From sinigrin)

• In pharmaceutical aid-
1. Flavouring agent- Vanillin, caumarin
2. Coloring agent- Saffran
3. Vehicle- Wild cherry
• In synthesis of
1. Steroidal diuretics
2. Sex hormones
3. Oral contraceptives
4. Corticosteroids

Cardiac Glycosides
• These are steroidal glycosides and show highly specific and
powerful action on cardiac muscle. The sugar part is attached at C-3
position of the steroid nucleus. The steroid aglycones are of two
types-
a) Cardenolides: They are C-23 steroids having an α,β-unsaturated
five membered lactone ring attached at 17β position. They are
present in digitalis, strophanthus, coleander, calotropis and
convallaria.
b) Bufadienolides: They are C-24 steroids having double unsaturated
six membered lactone ring at the 17α position. The name
bufadienolide has been derived from the generic name of toad,
bufo, since the compound bufalin was isolated from the skin of
toads.

a)
b)
O
O
2
1
3
4
5
6
7
8
91 0
1 1
1 2
1 3
1 4 1 5
1 6
1 7
1 8
1 9
2 0
2 1
2 2 2 3
2
1
3
4
5
6
7
8
910
11
12
13
14 15
16
17
18
19
O
O
20
21
22 23
24

Chemistry of Cardiac Glycosides
(Structural requirement)
• For maximum cardiac activity, the aglycone
should possess an α, β - unsaturated lactone
ring attached at β-position of 17-carbon of the
steroid nucleus and A/B and C/D ring junction
should have the cis-configuration.
• The sugar portion of the glycosides help in its
absorption and distribution in the body.
A B
C D

• Oxygen substitution on the steroid nucleus
affects the metabolism and distribution of the
glycosides.
• The more the no. of hydroxyl group, the more
rapid action of the glycoside in the body.
• Cardiac glycosides increase the force of
systolic contraction and decrease the heart
rate.

How cardiac glycoside works
Cardiac glycosides are therapeutically used
for their ability to increase the force of systolic
contraction.
An increase in contractility in the failing heart
results in a more complete emptying of the
ventricle and a shortening in the length of
systole.
Thus, the heart has more time to rest between
contractions.

• As the myocardium recovers as a result of
increased cardiac output and circulation, the
heart rate is decreased through a reflex vagal
effect.
• In addition, the improved circulation tends to
improve renal secretion, which relieves the
edema often associated with heart failure.

Necessity of the sugar portion:
• If the sugar portion is cleaved, yet aglycone
retains cardiac activity, however the sugar
portion (which increases the polarity) of the
glycoside is essential for its solubility
properties.
• i.e- absorption & distribution in the body
increase in the potency & toxicity of aglycone.

Digitalis
Source: Digitalis or foxglove is the dried leaf of Digitalis
purpurea (Fam. Scrophulariaceae). Its potency is such
that when assayed as directed 100 mg are equivalent
to not less than 1 USP digitalis unit (100 mg of USP
Digitalis reference standard). When digitalis is
prescribed, powdered digitalis is to be dispensed.
The leaves of other digitalis species D. dubia, D.
ferruginea, D. grandiflora, D. lanata, D. lutea, D.
mertonensis, D. nervosa, D. subalpina and D. thapsi also
show the presence of cardiac glycosides.

Powdered digitalis is digitalis dried at a
temperature not exceeding 60°C, reduced to a
fine or very fine powder and adjusted if
necessary, to confirm the official potency by
admixture with sufficient lactose, starch,
exhausted marc of digitalis or with a powdered
digitalis that has either a lower or a higher
potency.

Description & Distribution
The plant is a biennial herb probably indigenous
to central & southern Europe & naturalized in
various parts of Europe and in the northern &
western United States & Canada.

Cultivation of Digitalis
• In Germany, D. purpurea seeds which have been developed through
starin selection to yield plants with maximum drug potency and
with resistance to plant diseases are sown in greenhouse in March.
From the middle of May until the beginning of June, the young
plants are planted outside in relatively small plots (1 to 10 acres)
• The areas of cultivation of Digitalis must be centered around a
commercial drying unit at a distance not more than 30 Km.
• To ensure potency the leaves must be rapidly and gently dried at 50
to 60°C as soon as the plants are harvested.
• This procedure must be followed as the leaf contains hydrolytic
enzymes which if not rapidly inactivated, cleave the glycosidic
linkage thereby giving rise to the less active genins.
• Also excess heat may split off water from the tertiary hydroxyl
group position 14 of the steroid nucleus thereby forming the
inactive anhydro compound.

Harvesting
• The annual crop is harvested from the middle
of September to the end of October.

Constituents
• The Digitalis contains a large number of glycosides of which the
most important from medicinal view point are digitoxin, gioxin and
gitaloxin. The total conc. of these 3 glycosides varies appreciably
with the plant source and the conditions of growth.
• Also because all glycosides are derived from hydrolysis of some of
the sugars from the primary or parent glycosides occurring in the
leafs, their concentration depend on the manner of treatment of
the plant material following harvesting.
• Careful experiments have revealed that the secondary glycoside
content in the leaf is about 10 to 20% of the primary glycoside
concentration.
• Reported total concentrations of digitoxin, gitoxin, gitaloxin range
from 0.09 % in a poor quality Spanish sample to 0.225% in a
superior Japanese leaf; the average concentration approximates
0.16%.

• Nearly 30 other glycosides have been
identified in the drug. The major ones, in
terms of concentration, include: purpurea
glycoside A, purpurea glycoside B, gluco-
gitaloxin, gluco-digitoxigenin-bis-digitoxiside,
gluco-gitaloxigenin-bis-digitoxiside, gluco-
evatromonoside, gluco-gitoroside, gluco-
lanadoxin, digitalinum verum, gluco-
verodoxin, stropeside and verodoxin.

Composition of the principal Glycosides of Digitalis purpurea
Glycoisde Sugar
Derivatives of Digitoxigenin
Purpurea glycoside A
Digitoxin
gluco-digitoxigenin-bis-digitoxiside
gluco-evatromonoside
3 digitoxose, 1 glucose
3 digitoxose
Derivatives of Gitoxigenin
Purpurea glycoside B
Gitoxin
Gluco-gitoroside
Digitalinum verum
Stropeside
3 digitoxose
1 digitalose, 1 glucose
1 digitalose
Derivatives of Gitaloxigenin
Gluco-gitaloxin
Gitaloxin
Gluco-gitaloxigenin-bis-digitoxiside
Gluco-lanadoxin
Gluco-verodoxin
Verodoxin
3 digitoxose
1 digitalose

Assay
Digitalis and its preparations must be assayed
biologically to ensure their potency; however,
because crystalline glycosides are definite chemical
entities, they can be assayed chemically.
A number of test animals have been used in the
past: guniea pigs, frogs and cats. Animal now
employed in the assay procedure is the pigeon.
Standardization is determined by comparison of the
effect of a known dilution of the drug with that os a
similar dilution of the USP Digitalis Reference
Standard.

Uses:
• Digitalis is used in-
1. Congestive heart failure
2. Paroxysmal atrial trachycardia
3. Atrial flutter
4. Atrial fibrillation
5. Edema

Digitalis lanata
Digitalis lanata or grecian foxglove is the dried
leaves of Digitalis lanata, a plant indigenous to
southern and central Europe.
It is the source of digoxin and desacetyllanatosides.
However, nearly 70 different glycosides have been
detected in the leaves od D. lanata. All are
derivatives of 5 different aglycones, 3 of which also
occur in D. pupurea.

Composition of the principal
glycosides of D. lanata
Glycoside Sugars
Derivatives of Digitoxigenin
Lanatoside A
Acetyldigitoxin (α & β form)
Digitoxin
Gluco evatromonoside
Gluco-digitoxigenin-glucomethyloside
Gluco digifucoside
Neo-gluco-digifucoside
3 digitoxose, 1 acetyl group, 1 glucose
2 digitoxose, 1 acetyl group
3 digitoxose
1 glucomethylose, 1 glucose
1 fucose, 1 glucose
1 fucose, 1 glucose
Derivatives of Gitoxigenin
Lanatoside B
Gluco-gitoroside
Digitalinum verum

Glycoside Sugars
Derivatives of Gitaloxigenin
Lanatoside E
Gluco-lanadoxin
Gluco-verodoxin
Derivatives of Digoxigenin
Lanatoside C
Desacetyl Lanatoside C
Acetyldigoxin (α, β & γ forms)
Digoxin
Gluco-digoxigenin-bis-digitoxoside
3 digitoxose, 1 acetyl group
3 digitoxose
Derivatives of Diginatigenin
Lanatoside D 3 digitoxose, 1 acetyl group, 1 glucose

Structural formulae of several
cardenolide aglycones
O O
O H
CH3
HO
CH3
3
Digitoxigenin
O O
O H
C H 3
H O
C H 3
3
O R
G i t o x i g e n i n , R = H
G i t a l o x i g e n i n , R = C H O

O O
O H
C H 3
H O
C H 3
3
Digoxigenin
O H
O O
O H
C H 3
H O
C H O
3
Strophanthidin
O H
O O
O H
CH3
HO
CH2O H
3
O uabageninO H
HO
O H
O H
C H 3
H O
C H 3
3
S c i l l a r e n i n A
O O

Lanatoside C
O O
O
C H 3
H
H
H
O H
O H
C H 3
( C 6 H 1 0 O 3 ) 2 C 8 H 1 2 O 4 C 6 H 1 1 O 5
D i g i t o x o s e A c e t y l
d i g i t o x o s e
G l u c o s e

Strophanthus
• Strophamthus is the dried ripe seed of
Strophanthus kombe Oliver, or of
Strophanthus hispiduc DeCandolle (Fam.
Apocynaceae)
• It is native to africa. The seeds of strophanthus
have long been used by native africans in the
preparation of arrow poison.

Constituents
• K-strophanthoside, also known as strophoside, is the
primary glycoside in both strophanthus species.
• It is composed of genin (Strophanthidin), coupled to a
trisachcaride consisting of cymarose, β-glucose, α-
glucose.
• α-glucosidase removes the terminal α-glucose to yield
K-strophanthin-β and the enzyme strophanthobiase
(contained in the seed) converts this to cymarin plus
glucose.
• A mixture of these glycosides, existing in the seed in
concentrations up to 5 %, was formerly desihnated
strophanthin or K-strophanthin.

Ouabin
• Ouabin is a glycoside (C22H44O12.8H2O).
• It may be obtained from the seeds of
Strophanthus gratus.
• It is extremely poisonous.
• Ouabain is also known as G-strophanthus.

Uses
1. Cardioactive drug
2. As a diuretic
3. Arrow poison
4. In mild myocardial insufficiency where
digitalis is harmful

Anthraquinone Derivatives
Anthracene
O
O
4H
O
H H
Anthrone2H
O
H OH
Oxanthrone
-2H
O
O
Dianthrone
OH
H
Anthranol

CH3
OHO
O
OC6H11O5
Chrysophanol-8-glucoside
CH2OH
OHO
O
OC6H11O5
Aloe-emodin-8-glucoside
COOH
OHO
O
OC6H11O5
Rhein-8-glucoside
CH3
OH
O
OH
Emodinoxanthroneglucoside
HO
H O
C6H11O5

Chemical nature of Anthraquinone
Glycoside
• Must have an anthracene nucleus
• Sugar attached to aglycone either via oxygen
or C-C bond

Free anthraquinone aglycones exhibit
little therapeutic activity
• The sugar residue facilitates absorption and
translocation of the aglycone to the site of action.
• The anthraquinone and related glycosides are
stimulant cathartics and exert their action by
increasing the tone of smooth muscle in the wall
of the large intestine.
• Glycosides of anthranols and anthrones elicit a
more drastic action than do the corresponding
anthraquinone glycosides, and a preponderance
of the former constituents in the glycosidic
mixture can cause griping action.

Cascara sagrada
• Cascara sagrada or rhamnus purshiana is the
dried bark of Rhamnus purshinus (Fam.:
Rhamnaceae).
• Condition of use: The bark should be aged for at
least 1 year prior to use in medicinal
preparations.
• Reduced forms of emodin type glycosides are
present in the fresh bark, during the minimum 1
year storage period, these glycosides are
converted to the monomeric oxidized glycosides,
which exhibit a milder cathertic activity.

Distribution
• Cascara sagrada is a tree that attains a height
of 10 meters & indigenous to the pacific coast
of North America. Most of the present day
market supply comes from oregon,
washington and southern british columbia.

Constituents
• Two types of anthracene compounds have
been reported:
• Normal O-glycosides (based on emodin),
about 10 to 20 % and
• Aloinlike C-glycosides, representing about 80
to 90 % of the total.
• About a dozen such compounds have been
identified.

• Two of the C- glycosides are barbaloin and
deoxybarbaloin (chrysaloin)
• Four additional compounds of this type are
designated as cascaroside A, B, C and D.
• Cascarosides A & B are based on optical isomers
of barbaloin and cascarosides C & D are based on
optical isomers of chrysaloin
• All 4 of the cascarosides, being primary glycosides
of barbaloin and chrysaloin, are actually both O-
and C-glycosides.
• The remaining 4 to 6 anthracene derivatives
identified in the drug are normal O-glycosides,
based mostly on emodin.

C-10 R
Cascaroside A β OH
Cascaroside B α OH
Cascaroside C β H
Cascaroside D α H
O OH
CH2R
O
O
CH2OH
OH
OH
OH
O
CH2OH
OH
OH
OH

Casanthranol:
Casanthranol is a purified mixture of the
anthranol glycosides extracted from cascara
sagrada. It is also combined with surfactant
and/or hydrocolooids & used as a cathartic.
Such formulation include: alko-lubelax,
Comfolax plus etc.

Uses:
• As a cathartic
• Principal use is in the correction of habitual
constipation
• Not only acts as a laxative but restores natural
tone to the colon.

SENNA
• Senna or senna leaves consists of the dried leaf of
Cassia acutifolia, known in commerce as Alexandria
senna or of C. angustifolia, known in commerce as
Tinnevelly senna (Fam.: Leguminosae).
• Distribution: The palnts are low shrubs; C. acutifolia
grows wild near the Nile river from Aswan to Kordofan
and C. angustifolia grows wild in somalia, the Arabian
peninsula and India.
• Most of the commercial supply of the drug is collected
from plants cultivated in southern India (Tinnevelly);
some material is also produced in the Jammu district of
India and in Northwest Pakistan.

Cultivation: Senna is cultivated on wet lands
resembling rice paddies; infact rice is often one
crop of the season and senna is a later crop of
the same season.
Grades of Senna: Senna is graded according to
the size of the lead and the color of the leaflets:
blue-green leaves are best. Yellowish leaves are
poorest.

Constituents
O
O OHOH
OH OH
COOH
COOH
10
10'
H
H
Sennidin A(10 S, 10' S)
O
O OHOH
OH OH
H
H
Sennidin A (10 R, 10' R)
HOOC
HOOC

O
O
OH OH
OHOH
CO OH
HOO C
H H
Sennidin B (meso)

And other compounds
R' R'' 10-10'
SennosideA COOH COOH trans
SennosideB COOH COOH meso
SennosideC CH2OH COOH trans
SennosideD CH2OH COOH meso
O
O
O OH
OHO
R'
H H
C6H11O5
C6H11O5
R''

Constituents:
• The principle active constitents of senna are dimeric
glycosides whose aglycones are composed of aloe-
emodin and /or rhein. Those present in greatest conc.
are sennosides A and B, a pair of optical isomers whose
aglycones are rhein dianthrone (Sennidin A and B).
• Sennosides C and D are minor constituents having
dimeric aglycones composed of 1 molecule of aloe
emodin. Small quanities of monomeric glycoside and
free anthraquinones are also present.
• Senna pods also contain a useful active glycosides.
Some of primary glycosides in the pods have as many
as ten sugar molecules attached to a rhein dianthrone
nucleus.

Uses
• Senna is cathartic. The usual dose in 2g.
• Senna is stimulant laxative.
• Useful puragative for habitual constipation.

Aloe:
• Aloe or aloes is the dried latex (juice) of the
leaves of Aloe barbadensis (A. vera) known in
commerce as the Curacao aloe or of A. ferox
and hybrids of the species with A. africana
and A. Spicata, known in commerce as Cape
aloe (Fam-Liliacase) aloe yields not less than
50% water soluble extractive.
Source:

• The aloe are typical xerophytic plants that have
fleshy leaves, usually have spines at the margins
& resemble to some extent the agave or century
plant (Agave americana; fam-Amaryllidaceae).
• About 300 species of Aloe are known most of
which are indigenous to Africa. Many have been
introduced into the West Indies and Europe. The
official (BP, USP, EP) varieties of aloes are the
cape from South Africa and Kenya and the
Curacao, Aruba and Bonarie.
Description and Distribution:

• Aloe occurs on the market as opaque masses
that range from reddish black to brownish
black to dark brown in color. The taste of each
variety of aloe a nauseating and bitter. The
characteristics odor is disagreeable.
Characteristics:
Constituents:
• Aloe contains a number of anthraquinone
glycosides, the principle one of which is
barbaloin (aloe-emodin anthrone C-10
glycosides).

• O-glycosides of barbaloin with an additional sugar also
have been isolated from certain samples of Cape aloe.
These compounds have been designated as
Aloinosides.
• Free aloe-emodin and a free and combined anthranol
are also present.
• Chrysophanic acid has been detected in certain types
of the drug.
• The active constituents of aloe vary qualitatively and
quantitatively according to the species from which the
drug is obtained.
• Analysis have revealed that Curacao aloe is superior to
Cape aloe because it contains two and half times as
much aloe-emodin.

Constituents of Aloe
Barbaloin, aloe emodin, chrysophanic acid, free
and combined anthranol, aloinosides: O-
glycosides of barbaloin, resins, reputed to have
purgative action, aloesin & related chromo
derivatives; aloenin A and B-6-phenyl pyran-2
use analogs
O OH
CH2OH
OH
H C6H11O5
Barbaloin
O CH3
O
Glu
HO
CH3 O
Aloesin (Aloesone is the aglycone)

• Aloin is synonyms with Barbaloin, Socaloin,
Ugandaloin, Jafaloin, Cafaloin etc.
O
OR''R'O
O
OCH3
CH3
AloeninA:R'=H,R''=glucosyl
AloeninB:R'=glucosyl,R''=glucosyl-2-D-
coumarate

• Curacao aloe also contains an appreciable
amount of free and combined chrysophanic
acid not present in the other types.
• In addition to these physiologically active
compounds 10-30% aloe contains inactive
ingredients including large amounts (16-63%)
of a resinous materials plus volatile oil.

Uses:
• Aloe is a pharmaceutic aid for compound
benzoin tincture and a cathartic.
• Acts on the large intentine.
• Elicit a relatively drastic cathartic action and
some authorities advocate a preferential use
of other cathartic substances.

Aloe Vera Gel
• The fresh mucilagenous gel contained in the paranchymatous tissue
in the centre of the leaves of Aloe barbadensis (A. Vera) has been
used for years in the treatment of burns, abrasions and other skin
irritations.
• In 1935, the juice was recommended in treating third degree X-ray
burns, more recently, has been advocated for its moisturizing and
emollient effects.
• Commonly reffered as Aloe vera gel, a so called stabilized product is
now prepared from the central leaf tissue by many different
proprietary or patented methods, some of which involves
expression or solvent extraction under harsh condition.
• The resulting product is consequently extremely variable. Thus
while scientific studies have substantiated the cell proliferative
(wound healing) properties of fresh gel they have not verified such
activity in the stabilized product.

• The stabilized product is incorporated into a
wide range of preparations for external and
internal use, ranging from hand lotion to
frozen yogurt, and these are recommended
by their producers for alleviating conditions
ranging from headache to obesity.
• In spite of the mystique which, thanks to
prolific advertising, surrounds these stabilized
aloe gel products today, there is no scientific
or clinical evidence to support their
therapeutic utility.

Cyanophore Glycosides
Introduction:
Several glycosides that yield hydrocyanic acid as one of the products of
hydrolysis are commonly found in rosaceous plants. They are
sometimes designated as cyanogenic glycosides. Perhaps the most
widely dirsributed of these is amygldalin. It is important to note that
another of the hydrolytic products is benzaldehyde; thus, amygldalin-
containing drugs may also be classified in the aldehyde glycoside
group.
The common cyanophore/ cyanogenic glycosides are derivatives of
mandelonitrile (benzaldehyde-cynodydrin). The group is represented
in bitter almonds in Kernels of apricots, cherries, peaches, pulms and
many other seeds in Prunus Serotina. Both amygdalin and prunasin
yield D-mandelonitrile as the aglycone. Samburnigrin from Sambucus
nigra liberates L-mandelonitoile as its aglycone.

Amygdalin is a glucose rather than maltoside/enzymatic
hydrolysis of amygdalin
When amygdalin is hydrolyzed it forms 2
molecules of glucose. Although these are usually
written as linked in apparent disaccharide form,
one should note that a disaccharide sugar has
never been broken off from the molecule by any
known means of hydrolysis
The hydrolysis of amygdalin takes places in 3
steps which are as follows:

C
CN
H
O C6H10O4 O C6H11O5
Amygdalin
+ H2O
C
CN
O
H
C6H11O5
+ C6H12O6
M andelonitrile glucoside
+ H2O
C
CN
OH
H
+ C6H12O6
C O
H
+ HCN
Benzaldehyde
Mandelonitrile
Fig: Hydrolysis of Amygdalin

Upon hydrolysis amygdalin forms two identical
glucose units rather than a dissacharide
(maltose) unit. So it is a glucoside rather than
maltoside.
C
H 3 C C
H 3 C O C 6 H 1 1 O 5
N
L i n a m a r i n
L i n u m u s i t a t i s s i u m
H
C
O C 6 H 1 1 O 5
C N
D h u r r i n
S o r g h u m v u l g a r e

Medicinal Properties:
1. Preparations from plant materials containing
cyanogenic glycosides are widely employed as
flavoring agents.
2. Anticancer claims have also been made for an
amygdalin containing preparation known as
laetrile or vitamin B17. The FDA has not
recognized the efficiency of laetrile for
treatment of cancer although some states have
legalized its sale.
3. The possibility for control of sickle cell anemia
with cyanogenic glycosides has been noted.

Wild Cherry
Source: Wild cherry is the carefully dried stem
bark of Prunus serotina (Fam: Rosaceae). Prunus
is the classic name of the palm tree; serotina
means late or backward, referring to the time of
flowering and fruiting of the species. Wild
cherry is known as Prunus virginiana and as wild
black cherry tree.

Description and Distribution
• The plant is a tree that grows to a height of 30
meters or more in the eastern united states
and canada. The commercial supplies of the
drug come chiefly from Tenessee, Mississippi,
Virginia and North Carolina.

Constituents
• Prunasin (D-mandelonitrile glucoside) a
compound formed by the partial hydrolysis of
amygdalin
• Hydrolytic enzyme. Prunase
• P-caumaric acid
• Trimethyl gallic acid
• Starch and traces of volatile oil
• A resin that yields scopoletin on hydrolysis
• Benzoic acid

C O O H
H O
H O
C O O H
P - c o u m a r i c a c i d
O O
H 3 C O
H O
S c o p o l e t i n
C O O H
B e n z o i c a c i d
C O O H
O C H 3
O C H 3
H 3 C O
T r i m e t h y l g a l l i c a c i d

Uses
• In the form of syrup as a vehicle for cough
preparation
• Has sedative, expectorant properties
• Flavored vehicle

Isothiocyanate Glycoside
• The seeds of several cruciferous plants contain glycosides,
the aglycones of which are isothiocyanates.
• The aglycones may be either aliphatic or aromatic
compounds. Principal among these glycosides are sinigrin
from black mustard, sinalbin from white mustard and
gluconapin from rapeseed. When hydrolyzed by the
enzyme myrosin, they yield the mustard oils.
• Although the fixed oil content of these seeds exceeds the
amount of the volatile oil developed on hydrolysis, the
activity is caused by the latter.
• Mustard: Black mustard, sinapis nigra or brown mustard is
the dried ripe seed of varieties of Brassica nigra (Fam:
Cruciferae).

Distribution & Description
• The plants are annual herbs that have slender
erect stems, yellow flowers, pinnatified leaves
and some what four sided siliques with short
stalks.
• They are native to Europe and south western asia
but are naturalized and cultivated in temperate
climates in many countries and show
considerable variations in form. B. nigra is
cultivated in England and on the continent and B.
juncea is cultivated in India.

Constituents
• Although black mustard contains fixed oil (30
to 35%), its principal constituent is the
glycoside, sinigrin (potassium myronate),
which is accompanied by the enzyme myrosin.
• Upon the addition of water to the crushed or
powdered seeds, the myrosin effects the
hydrolysis of the sinigrin, as shown below:
C 3 H 5 C S
N O S O 3 K
C 6 H 1 1 O 5 + H 2 O
m y r o s i n
S C N
H 2
C C
H
C H 2 +
K H S O 4 + C 6 H 1 2 O 6S i n i g r i n
A l l y l i s o t h i o c y a n a t e
g l u c o s e
K a c i d s u l f a t e

• The allylisothiocyanate produced is volatile, it
is commonly called volatile mustard oil.
• Uses:
– Local irritant
– Emetic
– Externally rubefacient and vesicant
– Commercially as condiment

• White mustard: white mustard or
sinapis alba consists of the dried
ripe seed of Brassica alba (Fam:
Cruciferae)
• White mustard contains the
enzyme myrosin and a glucoside –
sinalbin which upon hydrolysis
yield acrinyl isothiocyanate, a
pungent tasting but almost
odorless oil that is much less
volatile that allyl isothiocyanate. It
also contains 20 to 25 % of fixed
oil.
H2CNCS
Acrinylisothiocyanate
(Parahydroxybenzylisothiocyanate)
OH

Saponin Glycosides
Characteristics:
• Widely distributed in higher plants
• Form colloidal solution in H2O that foam upon shaking
• Have bitter, acrid taste
• Irritating to the mucous membrane
• Capable to destroy RBC by hemolysis
• Toxic, especially to cold blooded animals and thus many are
used as fish poisons
• Yield aglycones known as sapogenins and sapogenins are
readily crystallizable upon acetylation. This process is useful
for the purifictaion of sapogenin
• The more poisonous saponins are often called sapotoxins.

Biosynthesis
of saponins
A ce ta te M ev alo n ate S q u a len e C h o les te ro l
O
O
H O
S p iro k etal s tero id n u c leu s (D io sg e n in )
H O
P e n tac y clic triterp e n o id ( - A m y rin )
F ig : B io s y n th e sis o f S ap o g e n in s

Glycyrrhiza/Licorice
• Glycyrrhiza is the dried rhizome and roots of
Glycyrrhiza glabra, known in commerce as
spanish Licorice or G. glabra, variety-
glandulifera known in commerce as Russian
licorice or of other varieties of G. glabra that
yield an yellow and sweet wood.

Constituents
• Principle constituent is glycyrrhizin
(glycyrrhizic acid), which is 50 times as sweet
as sugar. Upon hydrolysis, the glycoside loses
its sweet taste and is converted to the
aglycone glycyrrhetic acid and two molecules
of glucoronic acid.
• The C-20 epimer of glycyrrhetic
(glycyrrhetinic) acid is liquiritic acid

O
O
H
COOH
.Glu
AOGlu .A
20
Glu.A= Glucoronic Acid
HOOC
Epimer
Liquirrhizic acid
Glycyrrhizic acid/
Glycyrrhizinic acid
O
COOH
OH
OH
OH
OH
Glucoronicacid
O
O
HO
OR
CH3
R=Glycosyl,liquiritin
R=H,liquiritigenin
O
O
HO
Umbelliferone HO
Sitosterol

• Glycyrrhiza also contains isoquiritin,
isoquiritigenin, rhamnoliquiritin, various 2-
methyl isoflavones, coumarin derivative, 6-
acetyl-5-hydroxy-4-methyl coumarin, 5-15%
sugars (glusose, mannitol, sucrose) ,
asparagine

Uses
• Demulient, expectorant, flavoring agent to mask the taste of bitter drugs,
aloe, NH4Cl, quinine etc.
• Facilitate absorption of poorly absorbed drugs such as the anthraquinone
glycosides due to its surfactant property
• Commercially, licorice is added to chewing gums, chocolate candy,
cigarettes, chewing tobacco, smoking mixture etc.
• It increases the foaminess when added to bear.
• Recent studies have shown some pharmacological effect of glycyrrhetic
acid is used in dermatologic preparation for its anti-inflammatory activity
licorice root extract is employed in treating peptic ulcer and addison’s
disease (chronic adrenocortical insufficiency)
• Glycyrrhizin increases fluid and sodium retension and promotes potassium
depletion.
• Persons with cardiac problems and hypertension should avoid
consumptions of significant quantities of licorice.

Phenol Glycosides
• The aglycone group of many of the naturally
occuring glycosides are phenolic in nature.
Thus, Arbutin found in Uva ursi, chimaphila
and other ericaceous drugs, yield
hydroquinone and glucose upon hydrolysis.
Hesperidin, which occurs in various citrus
fruits and is include with the flavonol group,
may be classified as a phenolic glycosides.
O
O H
C 6 H 1 1 O 5
A r b u ti n
+ H 2 O
O H
O H
+ C 6 H 1 2 O 6
H y d r o q u i n o n e
G lu c o s e

Uva ursi
• Uva ursi or bear berry is the dried leaf of
Arctostaphylas uva-ursi or its varieties
cocatylis or notricha (Fam: Ericaceae).
• This plant is a procumbent evergreen shrub
indigenous to Europe, Asia and the northern
US and India.

Constituents
• In addition to glycoside Arbutin, the leaves
contain corilargin,pyroside, several esters of
arbutin, quercitin, gallic acid, elagic acid and
ursolic acid.
Ellagic acid
COOH
HO
Ursolic acid

O
O H
R O
O
O M e
O H
H e s p e rid in , R = g lu -rh a m
H e s p e ritin , R = H
O
O H
R O
O
O H
O H
R = H , Q u e rc e tin
R = R h a m n o s y l, Q u e rc e trin
COOH
HO
OH
OH
GallicAcid
C O O C H
C O HH
C O O C H
C H O H
C H
O
C O O C H 2
H O
H O
H O
H O
H O
H O
H O
H O
H O
C o r i l a g i n

Uses
• Uva ursi has a long history of use for its
diuretic and astringent properties. Extract of
Uva ursi was formerly as ingredient in some
proprietary formulations but its use in
prescription medications has been replaced by
more effective diuretic agents.
• The inclusion of Uva ursi and uther diuretic
materials in various products intended for
weight reduction is without recognized merit.

Alcohol Glycosides
Salicin
• Salicin is glycoside obtained from several species of
salix and populus. Most willow and poplar barks yield
salicin, but the principal sources are Salix purpurea and
S. fragilis. The glycoside, populin (benzoylsalicin), is
also associated with salicin in the barks of plants
belonging to the salicaceae.
• Salicin is hydrolyzed into D-glucose and saligenin
(Salicyl alcohol) by the enzyme emulsin. Salicin has
antirheumatic properties.
• Its action closely resembles that of salicylic acid and it
is probably oxidized to salicylic acid in the human
system.

• These properties of salicin clearly support
many folkloric uses of poplar and willow
barks.
O H
C O O H
S a l i c y l i c a c i d
O
C O O H
C
O
C H 3
A c e t y l s a l i c y l i c a c i d ( A s p i r i n )
O
C H 2 O H
C 6 H 1 1 O 5
S a lic in
H 2 O
C H 2 O H
O H
+ C 6 H 1 2 O 6
S a li g e n in
G lu c o s e
( O - h y d r o x y b e n z y l a lc o h o l )

Aldehyde Glycoside
• Vanilla is a drug that has an aldehydic aglycone as
its chief constituent Vanillin is the aglycone
developed during the curing of vanilla beans.
Vanillin is methyl protocatechuic aldehyde.
• Vanilla: Vanilla or vanilla bean is the cured full
grown unripe fruit of Vanilla planifolia; often
known in commerce as Mexican or bourbon
vanilla, or of V. tahitensis, known in commerce as
Tahiti vanilla (Fam: Orchidaceae).

Description and distribution
• The plant are perennial, climbing, dioecious
epiphytes attached to the trunks of trees by
means of aerial rootlets.
• The plant is native to the woods of eastern
Mexico but is cultivated in tropical countries
where the temperature does not fall below
18° C and where the humidity is high.

Constituents
• Green vanilla contains two
glycosides, glucovanillin and
glucovanillic alcohol.
• Glucovanillin is hydrolyzed into
glucose and vanillin and
glucovanillic alcohol is similarly
hydrolyzed into glucose and
vanillic alsohol which in turn
oxidizes to vanillic aldehyde
(Vanillin).
• Vanillin is the principal flavouring
constituents. Vanilla also contains
about 10 % of sugar, 10% of fixed
oil and calcium oxalate.
CH2OH
OMe
O C6H11O5
Glucovanillic alcohol
CHO
O
OMe
C6H11O5
Glucovanillin
(avenin, vanilloside)
CH2OH
OMe
OH
Vanillic alcohol

HC
O
OMe
C6H11O5
C
H
CH2OH
Coniferin
HC
OH
OMe
C
H
CH2OH CHO
OH
OMe
HC
OH
OMe
C
H
CH3
Coniferyl alcohol Vanillin
Isoeugenol
H2C C
H
CH2
OMe
OH
Eugenol

Uses
• Vanilla in the form of vanilla tincture, is used
as a flavouring agent and as a pharmaceutic
aid.
• It is also a source of vanillin.

Flavonoids & Flavonoid Glycosides
• The flavones, flavonols, flavonones, anthocyanidins (2-phenyl
benzopyrilium/ flavylium and leucoanthocyanidins ( flavon-3,4
diols)) and their glycosides are generally termed as flavonoids.
• The chalcones & isoflavones & their analogs are often grouped as
flavonoids.
• A large no. of different flavonoids occur in nature and these yellow
pigments are widely distributed throughout the higher plants.
• Rutin, quercitin and citrus, bioflavonoids; including hesperidin,
hesperitin, diosmin and naringen are among the best known
flavonoid constituents.
• More than 2000 of these compounds are known with nearly 500
occuring in free state.
• The flavones and their close relation are often yellow in color.
• The structure of the basic rings/carbon skeleton and some
commonly occuring flavonoid constituents are shown below-

O
O
B enzo- - P yrone (C hrom one)
O
O
Flavone
(2-phenyl- - chromone)
O
O
Iso fla v o n e
(3 -p h e n y l- - ch ro m o n e )
O
O
C6H5
OH
Flavonol
O
O
C6H5
Flavonone
O
O
X anthone
O
O
Flavanonal
OH
OH
OH
HO
OH
O
O
O H
O
O
O H
O HO H
A esculin

• Flavonoids are widely distributed in nature but
are more abundant in higher plants and young
tissues, where they occur in the cell sap.
• Many of these flavonoid compounds possess a
diversity of physiological and pharmacological
properties.
• They have also been extensively used as
chemotaxonomic markers.

Rutin & Hespiridin
• Have been termed as Vitamin P or permeability
factors.
• They have been used in the treatment of
conditions characterized by capillary bleeding and
increased capillary fragility.
• Claims have also been advanced for the value of
citrus bioflavonoids in treating symptoms of the
common cold.
• Few of these are included in some proportions as
dietary supplements.

OHO
OH O
O
OH
OH
C12H21O9
Rutin
OO
OH O
OH
OH
OH
Hesperidin
C12H21O9
OH O
O H O
O
O H
O H
Q u e r c e t r in
R h a m n o s e

Physico-chemical properties of
glycosides
1. Colorless, solid, amorphous, non-vollatile compounds (Flavonoid-yellow,
anthraquinone-red or orange)
2. They give positive reaction with Molisch’s and Fehlings solution test
(after hydrolysis).
3. They are water soluble compounds but insoluble in less polar organic
solvents.
4. Most of them have bitter taste (exception: populin, glycyrrhizin,
stevioside-which are sweet)
5. Glycosides are odorless except saponin.
6. Glycosides are generally hydrolyzed by boiling mineral acids or by using
enzymes such as
a) Emulsin Bitter almond, kernel seeds
b) Myrosin or Myrosinase black mustard seed
c) Rhamnase glycoside containing rhamnose as sugar part
7. Glycosides are optically laevorotatory.

Glycosides

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