Glycosides-1

‫عقر‬322

Pharmacognosy Dept. College of Pharmacy,

King Saud University 1436_1437 H
 Topics to be covered in PHG322

1. Alkaloids
2. Marine-derived Drugs
3. Glycosides
4. Poisonous plants
5. Herb-Drug Interaction

Exams and activities

1. 1st and 2nd Mid term exam (2 x 15 = 30 Marks)* Activities

(Quizzes, iClicker activities, or/and assignments with oral
discussion) (5 Marks)
2. Practical (30 Marks)
3. Final (40)

* The 2nd Mid term exam (10 Marks) + Activities (5 Marks

3/13/2018
calcd. as an average)Atallah F. Ahmed, PhD 2
 Teaching Policies
1. Be aware of your attendance from the beginning of
the session.

2. No sick leave certificates or other excuses will be

considered for physical attendance.

3. Dates of MidExams are fixed (unchangeble).

4. No provision for make up exams.

5. Prior to attending lectures some preparation is very

valuable to have a good score in iCliker monitored
session.

6. You have the opportunity to verify/clarify any points

you might not have fully understood in the class.
3/13/2018 Atallah F. Ahmed, PhD 3
 Phytochemistry-related
Learning pre-assessment

Pharmacognosy Dept. College of Pharmacy,

King Saud University 1436_1437 H
 Glycosides
Definition:
Glycosides are (usually) non-reducing organic compounds which
on hydrolysis by reagents (e.g. acids) or enzymes yield:
1. Glycone: one or more reducing sugars
2. Genin (Agylcone)

non-sugar glycosidic
sugar
linkage
(genin) (glycone)

The structure of a glycoside

Pharmacognosy Dept. College of Pharmacy,
King Saud University 1436_1437 H
 a and b Glycosides
• Since sugars exist in isomeric α and β forms.
• Both α and β Glycosides are thus theoretically
possible.

• Most of natural glycosides are of β Type.

• Some α linkage exists in carbohydrates such as

sucrose, glycogen and starch. Also the
glycoside K-strophanthoside (strophanthidin-link
to strophanthotriose moiety (Cymarose + β-
glucose + α- glucose).
Pharmacognosy Dept. College of Pharmacy,
King Saud University 1436_1437 H
 Classification & Nomenclature
1. According to the orientation of the glycosidic linkage: α-
glycoside (α-sugar) and β-glycosides (β-sugar).

2. According to the chemical group of the aglycone:

* Phenolic glycosides. * Saponin glycosides.
* Flavone glycosides. * Cyanophoric glycosides.
* Anthraquinone glycosides. * Thio-glycosides.
* Cardiac glycosides * Aldehydic glycosides.

3. According to the atom of the glycosidic linkage :

O-glycoside (OH group)
S-glycoside (SH group)
N-glycoside (NH group)
C-glycoside (C group)
Pharmacognosy Dept. College of Pharmacy,
King Saud University 1436_1437 H
3.1. Alcoholic or phenolic (OH) aglycone 
O-Glycoside
CH2 OH
CH 2OH
OH O-C6 H11 O5

C6 H12 O6 + -H 2O
Glycosidic linkage
Sugar
Salicin

3.2. Sulphur (S) containing aglycone 

S-Glycoside
Glycosidic linkage
SH
S C6 H11 O5
C6H12 O6 + CH2 CH CH2 C
CH2 CH CH2 C
N OSO3 K
Sugar N OSO3 K

Sinigrin
Pharmacognosy Dept. College of Pharmacy,
King Saud University 1436_1437 H
3.3. Nitrogen (N) containing aglycone 
N-Glycoside
NH2 NH2
OHCH2 O OH
N N N N
H +
H
N N N N
OH OH
H
OHCH2 O
Glycosidic linkage
H H

OH OH
Adenine
Adenosine

3. 4. C-Glycoside
HO O OH HO O OH

C6 H12 O6 +

CH2 OH CH2 OH
Glycosidic
linkage C6 H11 O5
Barbaloin
Pharmacognosy Dept. College of Pharmacy,
King Saud University 1436_1437 H
Training 1: which is the N-glycoside, C-glycoside, cyanogenic, and
phenolic glycoside?

glucovanillin
carmine

Nicotinamide-
D-ribonucleotid

amygdalin

Pharmacognosy Dept. College of Pharmacy,

arbutin
King Saud University 1436_1437 H
4. According to the nature of the simple sugar component (glycone ) of the
glycoside:
– Glucosides (the glycone is glucose).
– Galactosides (the glycone is galactose).
– Rhamnoside (the glycone is rhamnose).
– Arabinosides (the glycone is arabinose).

5. According to the number of monosaccharide molecules in sugar moiety:

– Monoside (one monosaccharide) e.g., salicin.
– Biosides (two monosaccharide) e.g., gentiobioside.
– Triosides (three monosaccharide) e.g., strophanthotriose.

6. Therapeutic classification i.e. according to the physiological or

pharmacological activity), e.g.
– Laxative glycosides.
– Cardiotonic glycosides.
– Analgesic glycosides.
Pharmacognosy Dept. College of Pharmacy,
King Saud University 1436_1437 H
7. According to the correlation to the parent natural glycoside:
– Primary (1ry) glycosides e.g., purpurea glycoside A
– Secondary (2ry) glycosides e.g., digitoxin.

8. According to the plant families.

9. According to the chemical nature of the aglycone:

a. Alcoholic and phenolic glycosides (aglycone: alcohol or phenol)
b. Aldehydic glycosides (aglycone: aldehydes).
c. Cyanogenic glycosides (aglycone: nitriles or HCN deriv.).
d. Anthracene or anthraquinone glycosides (aglycones:
anthracenes)
e. Steroidal glycosides (aglycone: steroid = cyclopentano-
phenanthrene deriv.) .
f. Coumarin glycosides (aglycone: benzo α-pyrone deriv. ).
g. Chromone glycosides (aglycone: benzo-δ-pyrone deriv. )
h. Flavonoid glycosides (aglycone: 2-phenyl chromone deriv.).
Pharmacognosy Dept. College of Pharmacy,
King Saud University 1436_1437 H
Training 2: which is the secondary glycoside?

Lantoside C

hydrolysis

+ glucose + acetic acid

Digoxin
Pharmacognosy Dept. College of Pharmacy,
King Saud University 1436_1437 H
9. According to the chemical nature of the aglycone (contd.):
i. Sulphur containing or thio- glycosides (aglycone contains sulphur).
J. Alkaloidal glycosides (aglycone: alkaloid) e.g., glucoalkaloids of
Solanum species.

Sugars in glycosides
• Monosaccharide (glucose in salicin)
• Disaccharides (gentiobiose in amygdalin).
• Trisaccharides (strophanthotriose).
• Tetrasaccharides (purpurea glycosides)
• Rare sugers (deoxy sugers e.g in cardiac glycosides)
• Sugar linked in one position to the aglycone rarely in 2
positions as sennosides.

Pharmacognosy Dept. College of Pharmacy,

King Saud University 1436_1437 H
Deoxy sugars (have a OH replaced with a hydrogen atom)
a) 6-deoxy sugars:
Methylpentoses e.g., α-L-rhamnose

b) 2,6-deoxy sugars (rare sugars) e.g., D.digitoxose and

D.cymarose

Pharmacognosy Dept. College of Pharmacy,

King Saud University 1436_1437 H
c) 2-deoxy sugars e.g., 2-deoxy-D-ribose

Chemical characters of 2-deoxy sugers:

• Give positive Schiff’s test for aldehydes.

• Give positive Keller-Kelliani test

Pharmacognosy Dept. College of Pharmacy,

King Saud University 1436_1437 H
 Physical & Chemical Properties
1- Diversity in structure makes various physical and
chemical properties:

a) Most glycosides are water and alcohol soluble.

b) Either insoluble or less soluble in non polar organic
solvents e.g, n-hexane, CH2Cl2.
c) When more sugar units included in the glycoside
molecule lead to more solubility in the polar solvents.

2- Glycosides DO NOT reduce Fehling’s solution. But

on hydrolysis, they give reducing sugars which can
reduce Fehling’s solution (C-glycosides are
exception).
Pharmacognosy Dept. College of Pharmacy,
King Saud University 1436_1437 H
3- Stability and Hydrolytic cleavage
Acid hydrolysis:
a- Acetal linkage between the aglycone and glycone is more
unstable than that between two individual sugars within
the molecule.
b- All glycosides (except C-glycosides) are hydrolysable by
acids and heat (non specific)
c- Glycosides containing 2-deoxy sugars are more
unstable towards acid hydrolysis even at room
temperature.
d- C-glycosides are very stable (need oxidative hydrolysis).
Alkali hydrolysis
(does not affect the glycosidic linkage):

Pharmacognosy Dept. College of Pharmacy,

King Saud University 1436_1437 H
3- Enzyme hydrolysis (specific):

▪ Enzymatic hydrolysis is specific (each glycoside has a

specific enzyme that can hydrolyse it).

▪ The same enzyme is capable to hydrolyze different

glycosides. But α and β sterio-isomers of the same
glycoside are not hydrolysed by the same enzyme.

▪ Emulsin is found to hydrolysed most β-glycoside

linkages. Thus, glycoside attacked by emulsin are
regarded as β-glycosides.

▪ Maltase and invertase are α-glycosidases, capable of

hydrolyzing α-glycosides only.
Pharmacognosy Dept. College of Pharmacy,
King Saud University 1436_1437 H
 Extraction & Isolation of glycosides

Extraction

• The most suitable solvent used for the extraction is

the hydro-alcohol (i.e. methanol or ethanol mixed
with different proportions of water)

• Non-polar organic solvents e.g. n-hexane are

generally used for preliminary defatting process.

• Unlike other constituents, glycosides are not

precipitated from aqueous solutions by lead acetate.

Pharmacognosy Dept. College of Pharmacy,

King Saud University 1436_1437 H
 Isolation involves:
1- Destruction of hydrolysing enzymes through:
• Drying at 100 C˚ for 15-30 min in hot air oven.
• Dropping plants in boiling alcohol for 10-20 min.
• Boiling with acetone.
• Cold acid pH treatment.
2. Defatting or purification of plant material (in case of seeds).
3. Extraction of glycosides by alcohol, water or hydro-alcohols.
Concentrate the extract. Add water and filter any precipitate.
4. Purification of the aqueous extract:
• Extract non glycosidal impurities by organic solvent.
• Water-soluble impurities (e.g. tannins) can be ppt by lead
acetate, filtered, followed by ppt of excess lead salts.
5. Isolation of the glycosides from the purified aqueous solution,
by crystallization or chromatographic separation.
. College of Pharmacy, King Saud University
1436_1437 H
Chemical tests depend on the nature of genins
1. Steroidal or cardiac glycosides  +ve Liebermann’s test
(steroidal structure).

2. Anthraquinone glycosides or aglycone  +ve Borntrager’s

test (characteristic red color with alkali.

3. Flavonoidal glycosides or aglycones Characteristic color

with NH4OH, AlCl3, and FeCl3.

4. Cyanogenic glycosides give upon hydrolysis hydrocyanic

acid (HCN) which can be easily tested by the change of
yellow Na picrate (Guignard’s test) paper to red color (Na
picramate).

5. Sulphur containing glycosides give black precipitate of

silver sulphide upon treatment with AgNO3 solution.

Pharmacognosy Dept. College of Pharmacy,

King Saud University 1436_1437 H
 Chemical tests depend on the sugar moiety
• Keller Killiani’s test is specific for 2-deoxy sugars:
• Specificity of action of the hydrolyzing enzymes is applied for
identification of the sugar moieties in the glycoside molecule.

1- Scillarin A [by acid hydrolysis]  Scillaridin A (genin) +

Scillabiose then: scillabiose [by scillabiase]  Rhamnose +
glucose.
2- Prunasin [by Prunase]  glucose + HCN + benzaldehyde
3- Amygdalin [by amygdalase]  prunasin + glucose
4- Myrosin enzyme is specific for the hydrolysis of thio-
glucosides e.g., sinigrin and sinalbin.
H CHO
OC 6 H 11 O 5
C

CN

amygdalin prunasin
benzaldehyde
Pharmacognosy Dept. College of Pharmacy,
King Saud University 1436_1437 H
Determination of the glycosidic linkages:
1. By the use of α and β glycosidases.
2. By acid hydrolysis of glycosides followed by an immediate
optical activity measurement of the resulting solution.

Color reactions based on the sugar moiety [2-deoxy

sugars]:
1. Keller Killiani test: glacial acetic acid + FeCl3 + H2SO4 →
brown ring free from red (acetic acid acquire blue).
2. Xanthydrol test: xanthydrol in glacial acetic containing 1%
HCl + glycoside [heat]→ red color.
N.B. Stability indicator after extraction (U.S.P.)

Pharmacognosy Dept. College of Pharmacy,

King Saud University 1436_1437 H
 Medicinal importance of glycosides:
• Cardiotonic: e.g. glycosides of digitalis,
strophanthus, and squill.
• Laxatives: e.g., anthraquinone glycosides of
senna, aloes, rhubarb, cascara, frangula.
• Counter irritants e.g., sinigrin thioglycoside
when hydrolysed into ‘allylisothiocyanate’
• Analgesics and Anti rheumatic e.g., salicin
• Reduction of capillary fragility e.g., flavonoid
glycosides, rutin, hisperidin.
• Anti-inflamatory: e.g., glycyrrhizin which has
additional demulcent and expectorant actions.
• Anticancer agent e.g., amygdalin known in the
U.S. as Laetrile.
Pharmacognosy Dept. College of Pharmacy,
King Saud University 1436_1437 H