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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5987_Библиотеки_им_академика_М_И_Перельмана.pdf
INTRODUCTION
Glycosides are defi ned as organic compounds derived by the replacement of the hydrogen atom
of the cyclic hemiacetal by an organic radical. They are obtained from plant or animal sources that
upon enzymatic or acid hydrolysis yield one or more sugar moieties along with nonsugar moiety.
The sugar moiety is called glycone and the nonsugar moiety is called aglycone or genin.
Aldohexopyranose
(acts as an hemiacetal)
(CHOH)
3
CHOH
HC
CH OH
2
O
Glycoside
(acetal)
(CHOH)
3
CHOCH
3
HC
CH OH
2
O⫹ CH OH
3
HCl
The hydroxyl group that is derived from carbonyl group by ring formation (i.e. C
1
in aldoses
and C
2
in ketoses) is involved in glycoside formation, and therefore, this hydroxyl group is known
as glycosidic hydroxyl group. The organic radical linked at glycosidic hydroxyl group is acid labile, i.e. if
a completely methylated glycoside is hydrolysed by acid, only the glycosidic methoxy group (acetal
type) is hydrolysed, while remaining methoxy groups (ether type) are not affected. Therefore, the
nature of the organic radical attached at the glycosidic hydroxyl group can be established by acidic
hydrolysis.
(CHOCH )
33
CHOCH
3
HC
CH OCH
23
O
(CHOCH )
33
CHOH
HC
O
HCl
CH OCH
23
The physicochemical and therapeutic properties of glycosides depend on the aglycone part,
the sugar moiety helps for the transportation of aglycone portion to the site of action. Glycosides
may exist in two anomeric forms called a and b.
Glycosides
3
CHAPTER
74
Pharmaceutical Chemistry of Natural Products
CHOH
␣-Glycoside -Glycoside
O
CHOH
O
CC
HH
RORO
CC
H
OR
Sugars involved in glycosides are of different types, but most commonly it is β-D-glucose.
Other sugars are galactose, mannose, rhamnose, digitoxose, cymarose, etc. The hydroxyl group of
aglycone may be alcoholic or phenolic and in some cases amines also.
CLASSIFICATION OF GLYCOSIDES
Glycosides may be classifi ed in different ways as described below:
Based on the Chemical Nature of Aglycone Part
Based on the chemical nature of aglycone moiety present in glycoside, they are classifi ed as follows:
1. Anthraquinone or anthracene glycosides
CH O
611 5
O
OOH
10
10
¢
R
1
R
2
OHO
OCH O
611 5
Rhein
OH
OHO
COOH
O
Aloe emodin
OH
OOH
CH OH
2
O
OH O OH
CH OH
2
Barbaloin
CH OH
2
H
H
H
H
HO
C
CH
C
C
C
OH
H
OH
O
R R 10-10’
Sennoside A COOH COOH Trans
Sennoside B COOH COOH Meso
Sennoside C CH OH COOH Trans
Sennoside D CH OH COOH Meso
12
2
2
Glycosides
75
2. Sterol or cardiac glycosides
Digitoxigenin
Gitoxigenin
Digoxigenin
O
O
1
2
3
4
5
6
7
8
9
10
11
12
14
15
16
17
18
19
20
21
22 23
A
B
C
D
13
HO
OH
OH
O
O
1
2
3
4
5
6
7
8
9
10
11
12
14
15
16
17
18
19
20
21
22 23
A
B
C
D
13
HO
OH
O
O
1
2
3
4
5
6
7
8
9
10
11
12
14
15
16
17
18
19
20
21
22 23
A
B
C
D
13
HO
OH
OH
Diginatigenin
Strophanthidin
Gitaloxigenin
O
O
1
2
3
4
5
6
7
8
9
10
11
12
14
15
16
17
18
19
20
21
22 23
A
B
C
D
13
HO
OH
O
O
1
2
3
4
5
6
7
8
9
10
11
12
14
15
16
17
18
19
20
21
22 23
A
B
C
D
13
HO
OH
O
O
1
2
3
4
5
6
7
8
9
10
11
12
14
15
16
17
18
20
21
22
23
A
B
C
D
13
HO
OH
OCHO
OH
OH
CHO
OH
13
O
O
D
14 15
16
17
18
20
21
22 23
24
Scillaridin-A
1
2
3
4
5
6
7
8
9
10
11
12
19
A
B
C
HO
OH
13
O
O
D
14 15
16
17
18
20
21
22 23
24
Hellebrigenin
1
2
3
4
5
6
7
8
9
10
11
12
CHO
A
B
C
HO
OH
OH
76
Pharmaceutical Chemistry of Natural Products
3. Saponin glycosides
O
O
H
COOH
Glucuronic acid
Glucuronic acid
Diosgenin
O
O
HO
CH
3
CH
3
CH
3
CH
3
Glycyrrhizinic acid
Glycyrrhizin is a mixture of calcium and
sodium salts of glycyrrhizinic acid
4. Isothiocyanate glycosides
HC
2
HC.H C
2
C S CH O
6115
N O SO K
3
Sinigrin
Silybin
O
O
O
OH
HO
OH O
OH
OCH
3
OH
5. Cyanogenetic or cyanophoric glycosides
O
CH O
6104
O
CH O
6115
C
CN
H
Amygdalin
Glycosides
77
6. Aldehyde glycosides
O
CHO
C
C
C
C
C
H
OH
H
OH
H
HO
H
H
O
HCO
3
Glucovanillin
CH OH
2
7. Steroidal glycoalkaloids
O
N
H
CH
3
H
3
C
CH
3
CH
3
HO
Solasodine
8. Coumarin and furanocoumarin glycosides
XanthotoxinCantharidin
O
O
O
O
CH
3
CH
3
O
O
H
O
OCH
3
78
Pharmaceutical Chemistry of Natural Products
9. Glycosidal bitters or miscellaneous glycosides
O
O
O
H
O
Lawsone
O
O
OH
OH
OH
OH
OR
CH
3
HC
3
OR
1
CH
3
HC
3
RO
2
HC HC
2
⫽
( -glucosyl)-
D
Gentiopicroside
RRR
Acetyl Gluconic
Methylbutyryl Acetyl Gluconic
Methylbutyryl H Gluconic
Tigloyl H Gluconic
12
Gymnemic acid I Tigloyl
Gymnemic acid II
Gymnemic acid III
Gymnemic acid IV
Based on the Chemical Nature of Sugar (Glycone) Moiety
Glycosides usually contain common type of sugars, however in few cases, sugars such as digitoxose
and cymarose are present. Based on the glycone moiety present in glycosides, they are classifi ed
as follows:
1. Glucosides: They contain glucose.
2. Rhamnosides: They contain rhamnose.
3. Pentosides: They contain pentose sugars such as ribose.
Based on the Therapeutic Activity Exerted by Glycosides
Glycosides are used for a variety of therapeutic purpose as given below:
1. Cathartics: Sennosides
2. Cardiotonics: Digitoxin, gitoxin
3. Analgesics: Salicin
4. Antirheumatics: Salicin
5. Anti-infl ammatory: Nimbidine
6. Anti-ulcer: Phenolic glycosides, apigenin
The cardiac glycosides are discussed in detail in Chapter 6, page 278.
Glycosides
79
Based on the Linkage Between Glycone and
Aglycone Moiety of the Glycoside
The glycosidal linkage is formed by the interaction of –OH group of glycone and hydrogen atom of
any of the radicals such as –CH, –OH, –SH and –NH (which is present on aglycone part) with the
elimination of a water molecule. The glycosidal linkage is named by placing the element which
connects the two units as prefi x. For example, in C-glycosides the carbon lies between glycone and
aglycone units of the glycoside.
Similarly, O-glycosides, S-glycosides or N-glycosides are named.
1. C-glycosides: They are formed by interaction of –CH group of aglycone and –OH group of
glycone with the elimination of a water molecule.
Glycone–C–aglycone
The C-glycosidic bond is covalent and is not hydrolysed by heating with dilute acids/alkalies.
It can be hydrolysed only by oxidative hydrolysis with ferric chloride.
OH O OH
H
C
C
C
C
H OH
HHO
OH
H
H
O
Example:
CH OH
2
CH OH
2
CH
Barbaloin
This type of glycosides is determined by modifi ed Borntrager’s test.
2. O-glycosides: They are formed by interaction of –OH group of aglycone and –OH group of
glycone with the elimination of a water molecule.
Glycone–O–glycone
As glycone and aglycone are linked through the electron-rich oxygen, the linkage is
susceptible for simple hydrolysis and hence it can be hydrolysed into aglycone and sugar by
treating with acid or alkali.
80
Pharmaceutical Chemistry of Natural Products
Sennoside A
Example:
O OH
COOH
O OH
COOH
10
O
O
CH O
6115
CH O
6115
10¢
This type of glycosides is determined by Borntrager’s test.
3. S- glycosides: They are formed by interaction of –SH group of aglycone and –OH group of
glycone with the elimination of a water molecule.
Glycone–S–aglycone
As glycone and aglycone are linked through the electron-rich sulphur, the bond is susceptible
for simple hydrolysis and hence it can be hydrolysed into aglycone and sugar by treating with
acid or alkali.
H C HC.H C
22
⫽ C S CH O
6115
N O SO K
3
Sinigrin
Example:
4. N-glycosides: They are formed by interaction of –NH group of base and –OH group of ribose/
deoxyribose (glycone) with the elimination of a water molecule. An example of N-glycosides
is nucleosides.
QUALITATIVE CHEMICAL TESTS FOR GLYCOSIDES
Cardiac Glycosides
1. Baljet’s test: A thick section shows yellow to orange colour with sodium picrate.
2. Legal’s test (test for cardenolides): To aqueous or alcoholic extract add 1 mL pyridine and 1 mL
sodium nitroprusside, pink to red colour appears.
3. Test for deoxy sugars (Keller–Kiliani test): To 2 mL of the extract add glacial acetic acid, one
drop of ferric chloride and concentrated sulphuric acid. Reddish brown colour appears at the
junction of the two liquid layers and the upper layer appears bluish green.
4. Liebermann’s test (test for bufadienolides): Mix 3 mL of extract with 3 mL acetic anhydride, heat
and cool the solution; add few drops of concentrated sulphuric acid. Blue colour appears.
Glycosides
81
Anthraquinone Glycosides
1. Borntrager’s test: To 3 mL extract add dilute sulphuric acid, boil and fi lter. To the cold fi ltrate
add equal volume of benzene or chloroform, shake well, separate the organic solvent and
add ammonia. The ammonical layer shows pinkish red colour.
2. Modifi ed Borntrager’s test (test for C-glycosides): To 5 mL extract add 5 mL of 5% ferric chloride
and 5 mL of dilute hydrochloric acid. Heat it for 5 minutes in boiling water bath. Cool and
add benzene or any organic solvent. Shake well, separate organic layer and add equal volume
of dilute ammonia. The ammonical layer shows pinkish red colour.
Saponin Glycosides
1. Foam test: Shake the drug extract or dry powder vigorously with water. Persistent foam is
observed.
2. Haemolytic test: Add the drug extract or dry powder to one drop of blood placed on glass slide.
Haemolytic zone appears.
Cyanogenetic Glycosides
Guignard reaction or sodium picrate test: Soak a fi lter paper strip in 10% picric acid, then in 10%
sodium bicarbonate and dry. In a conical fl ask, place moistened powdered drug, cork it and place
the fi lter paper in the slit in cork. The fi lter paper turns brick red or maroon. In this reaction,
hydrocyanic acid is liberated upon hydrolysis which changes sodium picrate to sodium purpurate
resulting in colour change from yellow to brick red or maroon.
Coumarin Glycosides
1. Alcoholic extract of the drug when made alkaline, shows blue or green fl uorescence.
2. Take moistened dry powder in a test tube. Cover the test tube with fi lter paper, soaked in
dilute sodium hydroxide. Keep it in water bath and after sometime expose the fi lter paper to
UV light. It shows yellowish green fl uorescence.
ISOLATION OF GLYCOSIDES
By continuous hot percolation the fi nely powdered crude drug is extracted using Soxhlet
apparatus with alcohol as solvent. To eliminate nonglycosidal impurities, the extract is treated
with lead acetate. By passing hydrogen sulphide gas through solution, the excess of lead acetate is
precipitated as lead sulphide. Extract is concentrated to get crude glycoside. From the crude extract,
the glycosides are obtained in pure form by the process of fractional crystallization, fractional
solubility and chromatographic techniques.