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Glycosides & Tannins

Glycosides
 Glycosides consist of a sugar residue covalently
bound to a different structure called the aglycone.
 The sugar residue is in its cyclic form and the
point of attachment is the hydroxyl group of the
hemiacetal function.
 The sugar moiety can be joined to the aglycone in
various ways:
1. Oxygen (O-glycoside)
2. Sulphur (S-glycoside)
3. Nitrogen (N-glycoside)
4. Carbon (Cglycoside)
 -Glycosides and -glycosides are distinguished
by the configuration of the hemiacetal hydroxyl
group.
 The majority of naturally-occurring glycosides
are -glycosides.
 O-Glycosides can easily be cleaved into sugar
and aglycone by hydrolysis with acids or
enzymes.
 Almost all plants that contain glycosides also
contain enzymes that bring about their hydrolysis
(glycosidases).
 Glycosides are usually soluble in water and in
polar organic solvents, whereas aglycones are
normally insoluble or only slightly soluble in
water.

 It is often very difficult to isolate intact


glycosides because of their polar character.

 Many important drugs are glycosides and their


pharmacological effects are largely determined by
the structure of the aglycone.
 The term 'glycoside' is a very general one which
embraces all the many and varied combinations
of sugars and aglycones.

 More precise terms are available to describe


particular classes. Some of these terms refer to:
1. the sugar part of the molecule (e.g. glucoside).
2. the aglycone (e.g. anthraquinone).
3. the physical or pharmacological property (e.g.
saponin “soap-like”, cardiac “having an action on
the heart”).
 Modern system of naming glycosides using the
termination '-oside' (e.g. sennoside).

 Although glycosides form a natural group in that


they all contain a sugar unit, the aglycones are of
such varied nature and complexity that glycosides
vary very much in their physical and chemical
properties and in their pharmacological action.
1. Anthracene glycosides

Anthracene

 A number of glycosides in which the aglycones are


anthracene derivatives occur as the pharmacologically
active constituents of several cathartics of plant origin;
e.g. cascara, rhubarb, aloe and senna.
 These anthracene glycosides are sometimes referred to as
the anthraquinone glycosides or the anthraglycosides.
 These anthraquinone derivatives are glycosides,
often glucosides or rhamnosides.
 The presence of the sugar residue is a prerequisite
for the pharmacological effects.
 Anthraquinones are colored substances and many
of them are used technically as dyes e.g. alizarin.
 Reduced forms of anthraquinones, which exhibit
keto-enol tautomerism, are often encountered.
 The anthracene derivatives occur in vegetable
drugs in different forms at different oxidation
levels; like anthraquinones, anthrones, anthranols,
or oxanthrones.
Interrelationship of anthraquinone derivatives
OH

Anthranol (enol form)

Taut.

O O
8 1

7 9 2
4H
A B C
6 10 3

5 4
Anthrone (keto form)
O
Anthraquinone 2 H

2H O

H OH

Oxanthrone
O
Dianthrone
 These anthracene compounds occur in these drugs or plant
materials in some cases as the aglycones of O-glycosides (e.g.
frangulin), and in other cases as the aglycones of C-glycosides
(e.g. aloin).
 Biosynthesis; natural anthraquinones are synthesized either via
the acetate-malonate pathway (like the medicinally important
purgative anthraquinones), or they are derived from shikimate
and mevalonate (like alizarin).
OH O OH O OH

OH

HO CH3

O O
Frangula emodin Alizarin
A. Anthraquinones

 Although anthraquinone is not used extensively in


medical practice, it is the starting material for the
preparation of several synthetic laxatives and
represent the basic structure of a number of
important laxatives and dyestuffs.
 Borntrager’s test is often used for their detection.
 The derivatives of anthraquinone present in
purgative drugs may be dihydroxy phenols such as
chrysophanol, trihydroxy phenols such as emodin
or tetrahydroxy phenols such as carminic acid.
O

O
Anthraquinone

OH O OH OH O OH

CH3 HO CH3

O O
Chrysophanol Emodin

HO

O
OH O CH3
OH
COOH
HO
OH

HO OH

OH O

Carminic Acid
B. Anthrones & Anthranols
 These reduced anthraquinone derivatives occur
either free or combined as glycosides.
 They are isomeric and one may be partially
converted to the other in solution.
 Anthranols are converted upon oxidation into
anthraquinones. Oxidation takes place in the crude
drug during storage especially if powdered.
 Schonteten’s test is often used for anthranols
(green fluorescence).
 Anthranols and anthrones are the main constituents
of chrysarobin, a mixture of substances.
OH OH OH OH O OH

CH3 CH3

Chrysarobin
(1,8-dihydroxy-3-methyl-9-anthrone; 3-methyl-1,8,9-anthracenetriol)
C. Oxanthrones OH O OH

H OH

 These are intermediate products between


anthraquinones and anthranols.
 They give anthraquinones on oxidation with
hydrogen peroxide.
 An oxanthrone has been reported as a constituent
of cascara bark.
-D-glucose–O O OH
D. Dianthrones
 These are compounds derived from COOH
two anthrone molecules, which may COOH

be identical or different.
 They are important aglycones in
- -glucose–O
D O OH
species of Cassia, Rheum and
Sennosides
Rhamnus.
 One of the best known is sennoside
derived from two molecules of
glucose and two molecules of rhein-
anthrone.
 On hydrolysis, sennoside yields the
aglycone sennidin.
E. Aloin-type or C-glycosides
OH O OH

 Aloin (Barbaloin) was obtained


from species of Aloe. OH

 It is strongly resistant to normal HO

acid hydrolysis. O

 In aloin, the sugar is joined to OH Aloin


HO
aglycone with a direct C-C linkage OH
(a C-glycoside).
 Two aloins (A and B) are known
and arise from the chiral centre at
C-10.
2. Saponin glycosides
 A group of plant glycosides known as saponins
share in varying degrees, two common
characteristics:
(a) They foam in aqueous solution.
(b) They cause haemolysis of red blood cells.

 The aglycones of the saponins are collectively


referred to as Sapogenins. The more poisonous
saponins are often called Sapotoxins.
 Plant materials containing saponins have long
been used in many parts of the world for their
detergent properties for example, in Europe, the
root of Saponaria officinalis (Fam.
Caryophyllaceae) and in South America, the bark
of Quillaia saponaria (Fam. Rosaceae). Such
plants contain a high percentage of the glycosides
known as saponins (Latin Sapo, means Soap)
which are characterized by their property of
producing a frothing aqueous solution.
Properties:
 Saponins form colloidal solution in water
(hydrophilic colloids) which froths upon shaking.
These substances modify and lower the surface
tension and therefore foam when shaken. This has
led to their use to increase the foaming of beer.

 Practical industrial applications of saponins


include their use in cleaning industrial equipment
and fine fabrics and as powerful emulsifiers of
certain resins, fats and fixed oils.
 In general, they have a bitter, acrid taste and
drugs containing them are usually sternutatory
(causing or producing sneezing) and irritating to the
mucous membranes of eyes and nose.
 Characteristic for all saponins is their ability to
cause haemolysis of red blood corpuscles and to
destroy them. When injected into the blood
stream, they are highly toxic.
 When taken by mouth, Saponins are
comparatively harmless, being not absorbed from
the intestinal tract. Sarsaparilla, for example, is
rich in saponins but is widely used in the
preparation of nonalcoholic beverages.
 Saponins are toxic especially to cold-blooded
animals e.g. frogs. Many are used as fish-poisons.
 The actual cause of the haemolysis:
The red blood cells carry sterols in their
membranes, and when brought into contact with
saponins, the sterols of the RBCs are precipitated
and the colloidal chemical properties of the
membrane are so altered as to give hemoglobin
passage to the surrounding medium.

 Saponins have a high molecular weight and their


isolation in a state of purity presents some
difficulties.
 Structure of Saponins:
According to the structure of the aglycone or
sapogenin, two kinds of saponin are recognized:
1. The steroidal type (commonly tetracyclic
triterpenoids, C-27).
2. The triterpenoid type (pentacyclic triterpenoids,
C-30).
 Both of these have a glycosidal linkage at C-3
and have a common biosynthetic origin via
mevalonic acid and isoprene units.
21

18 26

25
17
19
27
1

3
Steroid skeleton 29 30

25 26
28

3 27
Pentacyclic triterpenoid skeleton

23 24
A. Steroidal saponins

 The steroidal saponins are less widely distributed


in nature than the pentacyclic triterpenoid type.
 Steroidal saponins are of great pharmaceutical
importance because of their relationship to
compounds such as the sex hormones, cortisone,
diuretic steroids, vitamin D and the cardiac
glycosides.
 Examples: Diosgenin (Dioscorea sylvatica),
Sarsapogenin (Smilax sp.).
B. Pentacyclic triterpenoid saponins
 Triterpenoid saponins my be classified into three
groups represented by -amyrin, -amyrin and lupeol.
 Examples: Primulagenin (Primula sp.), Quillaiac acid
(Quillaia saponaria) and Glycyrrhetinic acid
(Glycyrrhiza sp.).

20
19
E

13 17
D
14

Amyrin Amyrin Lupeol


3. Coumarin glycosides
5 4
6 3

2
7
O O
8
1
Coumarin
(Benzo--pyrone)

 The coumarins are shikimate-derived metabolites.


 The majority of the coumarins are oxygenated at position
C7.
 Coumarins have a limited distribution in the plant
kingdom and have been used to classify plants according
to their presence (chemotaxonomy).
 Coumarins are commonly found in the plant
families Apiaceae, Rutaceae, Asteraceae and
Fabaceae.
 Some coumarins are phytoalexins and are
synthesized de novo by the plant following
infection by a bacterium or fungus.
 Phytoalexins: any of a group of compounds
formed in plants in response to fungal infection,
physical damage, chemical injury, or a pathogenic
process. Phytoalexins inhibit or destroy the
invading agent.
H3CO
 These phytoalexins are
broadly antimicrobial; for
example, scopoletin is
HO O O
synthesized by the potato
(Solanum tuberosum) Scopoletin
following fungal infection.
OCH3 O

 Khellin is an isocoumarin
(chromone) natural product
from Ammi Visnaga
O
(Apiaceae) and has activity as O CH3

a spasmolytic and vasodilator. OCH3

Khellin
 It has long been known that
animals fed sweet clover OH OH
(Melilotus officinalis,
Fabaceae) die from
haemorrhaging. The poisonous O O O O
compound responsible for this Dicoumarol
adverse effect was identified
as dicoumarol.
 A number of compounds have
been synthesized based on the OH O
dicoumarol structure, e.g.
warfarin, which is widely CH3

used as anticoagulant.
O O Warfarin
 The psoralens are coumarins
that possess a furan ring and
are sometimes known as
O O O
furanocoumarins. e.g.
psoralen and bergapten. Psoralen

 These compounds may be


produced by the plant as a OCH3
protection mechanism against
high doses of sunlight and
some coumarins are
formulated into sunscreens O O O
and cosmetics for this
purpose. Bergapten
4. Flavonoid glycosides

 Biosynthesis:
flavonoids are products from a cinnamoyl-CoA
(C6C3, precursor from the shikimate pathway)
starter unit, with chain extension using three
molecules of malonyl-CoA.
 Flavonoids are therefore of mixed biosynthesis,
consisting of units derived from both shikimate
and acetate pathways.
 The triketide starter unit undergoes cyclization by
the enzyme chalcone synthase to generate the
chalcone group of flavonoids. Cyclization can
then occur to give a pyranone ring containing
flavanone nucleus, which can either have the C2-
C3 bond oxidized (unsaturated) to give the
flavones or be hydroxylated at position C3 of the
pyranone ring to give the flavanonol group of
flavonoids. The flavanonols may then be further
oxidized to yield the anthocyanins, which
contribute to the brilliant blues of flowers and the
dark colour of red wine.
 The flavonoids contribute to many other colors
found in nature, particularly the yellow and
orange of petals; even the colourless flavonoids
absorb light in the UV spectrum (due to their
extensive chromophores) and are visible to many
insects. [A chromophore is the part (or moiety)
of a molecule responsible for its color].
 It is likely that these compounds have high
ecological importance in nature as colour
attractants to insects and birds as an aid to plant
pollination.
 Certain flavonoids also markedly affect the taste
of foods: for example, some are very bitter and
astringent such as the flavanone glycoside
naringin, which occurs in the peel of grapefruit
(Citrus paradisi). Interestingly. the closely related
compound naringin dihydrochalcone, which
lacks the pyranone ring of naringin, is
exceptionally sweet, being some 1000 times
sweeter than table sugar (sucrose).
 the flavonoids have important dietary
significance because, being phenolic compounds,
they are strongly antioxidant.

 Many disease states are known to be exacerbated


by the presence of free radicals such as
superoxide and hydroxyl, and flavonoids have the
ability to scavenge and effectively ‘mop up’ these
damaging oxidizing species.
 Foods rich in this group have therefore been proposed to
be important in ameliorating diseases such as cancer and
heart disease (which can be worsened by oxidation of
low-density lipoprotein); quercetin, a flavonoid present
in many foodstuffs, is a strong antioxidant. Components
of milk thistle (Silybum marianum), in particular silybin,
are antihepatotoxins; extracts of milk thistle are
generally known as silymarin.

OH O
OH

HO O HO O OCH3
OH O

OH OH OH

OH O OH O Silybin
Quercetin
Some action and therapeutic uses of
flavonoids

 Many flavonoid containing plants are:


1. Diuretic.
2. Antispasmodic.
3. Diaphoretic.
4. Increase tensile strength of capillary walls.
5. Free radical scavengers.
5. Cyanogenetic glycosides
(Cyanide glycosides)
 Cyanogenesis is the ability of certain living
organisms, plants in particular, to produce
hydrocyanic acid (HCN, prussic acid).
 Cyanogenesis in plants is a chemical defense
mechanism against organism damaging or feeding
on plant tissues and lead to release of HCN gas,
which is toxic.
 They are distributed in over 2000 plant species
belonging to 110 families.
 These compounds, in presence of enzymes such
as -glucosidase, lose their sugar portion to form
a cyanohydrin which, in the presence of water
and hydroxynitrile lyase, can undergo hydrolysis
to give benzaldehyde and the highly toxic
hydrogen cyanide (HCN).
 The sugar portion of the molecule may be a
monosaccharide or a disaccharide such as
gentiobiose or vicianose. If a disaccharide,
enzymes present in the plant may bring about
hydrolysis in two stages, as in the case of
amygdalin.
R1 CN

R2
OSugar
 They are derivatives of -hydroxynitrile or 2-
hydroxynitrile (cyanohydrins).
 In all cases the first sugar attached to the aglycone is
-D-glucose.
 R1 and R2 are often different residues resulting in
pairs of C-2 epimers.
(Epimers are diastereomers that differ in configuration at only one
of their stereogenic centers).
 Most cyanogenetic glycosides are biosynthetically
derived from the amino acids: valine, leucine, isoleucine,
tyrosine or phenylalanine.
 Cyanogenetic glycosides are easy to detect with a strip
of filter paper impregnated with reagents able to give a
color reaction with the hydrocyanic acid released upon
crushing the plant material (e.g., picric acid/sodium
carbonate or benzidine/cupric acetate).
 Although hydrocyanic acid is a violent poison, it is
important to remember that oral intake of cyanogenetic
drugs does not necessarily cause severe intoxication, this
is because the range of dangerous concentrations (0.5-
3.5 mg/kg) can only be achieved by rapid and massive
ingestion of plant parts rich in cyanogenetic glycosides.
 Examples:
1. Amygdalin in bitter almonds (Prunus amygdalus). It is
biosynthetically derived from phenylalanine.
2. Linamarin in linseed (Linum usitatissimum). It is
biosynthetically derived from valine.

HO
CN O
HO
HO HO O
CH3
O OH O
O HO
CH3 HO O CN
OH
OH
HO H
OH Amygdalin

Linamarin
6. Steroidal cardioactive glycosides
 Cardiac glycosides are a group of natural products
characterized by their specific effect on myocardial
contraction and atrioventricular conduction.
 In large doses they are toxic and bring about cardiac
arrest in systole, but in lower doses they are
important drugs in the treatment of congestive heart
failure.
 They have a diuretic activity. Since, the improved
circulation tends to improve renal secretion, which
relieves the edema often associated with heart
failure.
 Distribution in nature
 Cardiac glycosides occur in small amounts in
the seeds, leaves, stems, roots or barks of plants
of wide geographical distribution, particularly of
the Fam. Apocyanaceae (e.g. seeds of
Strophanthus, roots of Apocynum and fruits of
Acokanthera); others are found in the
Scrophulariaceae (e.g. leaves of Digitalis sp.),
Liliaceae (e.g. scales of the bulbs of Urginea and
Convallaria), and Ranunculaceae (Adonis).
 Cardiac glycosides are also found in animals only
in exceptional cases: Bufadienolides occur in
toads (Bufo).
Lactone ring
 Structure of glycosides 12
18

11 13 17
19
C D 16
1 14
9
2 15
10 8
A B
3
5 7
O
4 6

Sugar moiety

 The structure comprise a steroidal aglycone of the


(C23) cardenolide type or of the (C24)
bufadienolide type, and a sugar moiety, most
often an oligosaccharide.
A. Structure of the aglycones

 All of the aglycones have in common the classic,


tetracyclic, steroidal nucleus.
 The A, B, C and D rings normally have a cis-
trans-cis configuration or less often, a trans-
trans-cis configuration.
 Also common to all the aglycones is the presence
of two hydroxyl groups: one is a 3 secondary
alcohol, the other is a 14 tertiary alcohol.
 All of the aglycones have a  constituent at C-17:
an ,-unsaturated lactone.
O

24
O O
O 23
23
21 21
22 22
20 20

17 17
16 16

14 14
15 15

Lactone ring of Lactone ring of


Cardenolide Bufadienolide

 The size of the lactone ring distinguishes two groups of


aglycones: the C23 cardenolides with an ,-unsaturated
-lactone (= butenolide) and the C24 bufadienolides with
a di-unsaturated -lactone (= pentadienolide).
B. Structure of the sugar moiety
 The sugar moiety is generally linked to the aglycone
through the hydroxyl group at C-3.
 The majority of the saccharides found in cardiac
glycosides are highly specific:
1. 2,6-dideoxyhexoses, e.g. D-digitoxose
2. 2,6-dideoxy-3-methylhexoses, e.g. D-diginose
3. 6-deoxyhexoses, e.g. L-rhamnose
4. 6-deoxy-3-methylhexoses, e.g. D-digitalose
5. Hexose, e.g. glucose (when these is a glucose unit, it is always
terminal).
 The sugars can modify the activity (potency, toxicity),
the solubility, the diffusion through membranes, the rate
of absorption and transportation of the glycosides.
C. Structure-Activity Relationships (SAR)
 The cardiac activity is linked to the aglycone.
 The sugar moiety does not participate directly in the
activity, but its presence enhances the activity and
modulates it by modifying the polarity of the compound.
 The presence of a certain number of structural elements is
required for, or at least favorable, to the activity:
1. The lactone at C-17, and it must be in the  configuration.
2. The configuration of the rings. The activity is maximized
when the A, B, C and D rings are in the cis, trans, cis
configuration. The C and D rings must be cis fused.
3. The substituents. The inversion of the configuration at C-
3 diminishes the activity, but 3-deoxy compounds are not
completely inactive.
O O

C D

A B OH

HO
O
CH3
O
CH3 H

OH H
H
H
HO Digitoxigenin
A/B cis - B/C trans - C/D cis
H
 Biosynthetic origin

 Aglycone of the cardiac glycosides are derived


from mevalonic acid but the final molecules arise
from a condensation of a C21 steroid with a C2
unit (the source of C-22 and C-23).
Bufadienolides are condensation products of a
C21 steroid and a C3 unit.
 Color reactions
 They can be due to the sugars or to the aglycone:
A. Color reactions of the sugars. The only color reactions of
the sugars that are of interest are those specific to 2-
deoxyhexoses. e.g. Keller-Kiliani test.

B. Color reactions of the aglycones (steroidal nucleus).


These are positive with any compound containing a
steroidal nucleus including cardenolides or bufadienolide:
1) Antimony trichloride (SbCl3)
2) Liebermann's test (for bufadienolides)
C. Color reactions of the aglycones (lactone ring).
These are characteristic for cardenolides having a
five-membered lactone ring:
1. Legal's test
2. Raymond's test
3. Kedde's test
4. Baljet's test
Pharmacological properties
 Cardiac glycosides increase the force and speed of
contraction of the heart. In patients with cardiac
insufficiency, this positive inotropic effect
translates into 1an increase in cardiac output, 2an
increase in cardiac work capacity without any
increase in oxygen consumption, 3a decrease in
heart rate, and, indirectly, 4a decrease in arterial
resistance. (MOA) The glycosides are thought to
act at the membrane level, by inhibition of the Na-
K ATPase, which would result in an increase of the
intracellular calcium ion concentration.
Therapeutic indications

 Cardiac glycosides are currently indicated for:


1. Cardiac insufficiency with low output (generally
in combination with diuretics), particularly when
there is atrial fibrillation.

2. Supraventricular rhythm abnormalities: to slow


down or decrease atrial fibrillation or flutter.
Examples
 Strophanthus glycosides
The name Strophanthus is
derived from the Greek
strophos (a twisted cord or
rope) and anthos (a flower).
e.g. Strophanthus kombe
The principle glycosides are:
1. K-strophanthoside
2. K-strophanthin-
3. Cymarin
O
O

CH3

O
CH H

H OH

O
OH

Cymarose-D-glucose -D-glucose

Cymarin

K-strophanthin-

K-strophanthoside
 Squill glycosides
Urginea maritima (L.)
0.1%  2.4% total bufadienolides,
15 glycosides
 White variety: average 0.2%-0.4%
proscillaridin A, scillaren A,
glucoscillaren A (aglycone:
scillarenin)
scilliphaeoside, scilliglaucoside
 Red variety: < 0.1%
scilliroside and glucoscilliroside
(aglycone: scillirosidin);
proscillaridin A and scillaren A as in
the white variety
Pharmacological properties of squill

 White squill:
it is an expectorant, but it also possesses emetic,
cardiotonic (proscillaridin A), and diuretic
properties.
 Red squill:
it is used as a rat poison (scilliroside), because
rodents lack the vomiting reflex, which makes
red squill particularly lethal to these animals.
O

CH3

CH3 OH

H OH

-D-glucose–O Scilliroside
O CH3

O
(3,6)-6-(Acetyloxy)-3-(-D-glucopyranosyloxy)-8,14-dihydroxybufa-4,20,22-trienolide
 Digitalis glycosides
Several species of Digitalis yield pharmacologically
active principles. The most important of these species are
Digitalis purpurea and Digitalis lanata.
1. Digitalis purpurea folium (Red foxglove leaves)
0.15%  0.4% total cardenolides,  30 glycosides
Purpurea glycosides A and B (60%), digitoxin (12%),
gitoxin (10%) and gitaloxin (10%).
2. Digitalis lanata folium (White foxglove leaves)
0.5%  1.5% total cardenolides,  60 glycosides
Lanatosides A and C (50%), lanatosides B, D, E as well
as digoxin and digitoxin.
 Digitoxin is a cardiotonic  Digoxin is the most widely
glycoside obtained from D. used of the cardiotonic
purpurea, D. lanata. glycosides, and it is obtained
 It is the most lipid-soluble of from the leaves of D. lanata.
the cardiac glycosides used in  It is a highly potent drug and
therapeutics. should be handled with
 The major pharmacokinetic exceptional care.
parameters for digitoxin  Digoxin tablets are 60 to
include complete oral 80% absorbed.
absorption, which  Digoxin is indicated when the
distinguishes it from other risk of digitalis intoxication is
cardiac glycosides. great, since it is relatively short-
acting and rapidly eliminated
 Digitoxin may be indicated in
when compared with digitoxin.
patients with impaired renal
function.
Digitalis purpurea
7. Tannins
 Historically, the importance of tannin-containing
drugs is linked to their tanning properties, in
other words their ability to transform fresh hides
into an imputrescible material: leather.

 Tannins are "phenolic natural products that


precipitate proteins from their aqueous solutions".
 The consequence of tanning is the formation of
bonds between the collagen fibers in the hide,
which imparts resistance to water, heat, and
abrasion. This capability of tannins to combine
with macromolecules explains why they
precipitate cellulose, pectins, and proteins; it
also explains their characteristic astringency
and tartness: by precipitating the glycoproteins
contained in saliva, tannins make the latter lose
its lubricating power.
 Most true tannins have molecular weights
from about 1000  5000.
Pseudotannins
 They are compounds of lower molecular weight
than true tannins and they do not respond to the
goldbeater's skin test.
 Examples of drugs containing Pseudotannins are:
 Gallic acid: Rhubarb

 Catechins: Guarana, Cocoa

 Chlorogenic acid: Mate, Coffee

 Ipecacuanhic acid: ipecacuanha


OH
COOH

HO O
OH

HO OH OH
OH OH
Gallic acid Catechin

HOOC OH

OH
O

HO O OH

OH
Chlorogenic acid
Function of tannins in plants

1. Tannins are considered the source of energy


through their oxygen content.
2. They serve as a protective to the plant (plant
antiseptics).
3. They may have function in respiratory activity, i.e.
in the mechanisms of hydrogen transfer in plant
cells.
4. Tannins play an important part in the acceptance of
many foods and beverages by consumers e.g. tea,
cocoa.
Classification of tannins

 In higher plants, two groups of tannins are


generally distinguished, which differ by their
structure, as well as their biosynthetic origin:
hydrolysable tannins and condensed tannins.

 Hydrolysable tannins
Hydrolysable tannins are esters of a sugar (or
related polyol) and of a variable number of
phenolic acid molecules.
 The sugar is most generally glucose.
 The phenolic acid is either gallic acid, in the case
of gallitannins, or Ellagic acid, in the case of the
tannins conventionally referred to as
ellagitannins.
 Ellagic acid can arise by lactonization of
hexahydroxydiphenic acid (= HHDP) during
chemical hydrolysis of the tannin.
 Hydrolysable tannins were formerly known as
pyrogallol tannins, because on dry distillation
gallic acid and similar components are converted
into pyrogallol.
 Biosynthetically, gallic acid (= 3,4,5-
trihydroxybenzoic acid) arises from the
metabolism of shikimic acid.
 Examples of drugs containing Hydrolysable
tannins:
Gallitannins: rhubarb, cloves, Chinese galls,
Turkish galls, hamamelis, chestnut and maple.
Ellagitannins: pomegranate rind, pomegranate
bark, eucalyptus leaves, and oak bark.
OH OH

HO HO
COOH

O
HO COOH O

HOOC OH O
HO OH O
OH
OH OH
Gallic acid
OH OH

Hexahydroxydiphenic acid Ellagic Acid

HO OH

OH
Pyrogallol
 Condensed tannins (proanthocyanidins)
Condensed tannins or proanthocyanidins are
polymeric flavans. They consist of flavan-3-ol
units linked together by carbon-carbon bonds,
most often 48 or 46, which result from
coupling between the electrophilic C4 of a
flavanyl unit from a flavan-4-ol or flavan-3,4-diol
and a nucleophilic position (C-8, less commonly
C-6) of another unit, generally a flavan-3-ol.
 Unlike hydrolysable tannins, these are not readily
hydrolyzed to simpler molecules and they do not
contain a sugar moiety.
OH OH

HO O HO O
OH OH

OH OH

OH OH OH

(+) Catechin (catechol) Flavan-3,4-diol structure

OH

HO O
OH

OH OH
OH
HO O
OH

OH

OH

A dimeric structure
 Biosynthetically, flavonoids are derived from
acetate and shikimate pathways.
 Condensed tannins occur due to polymerization
(condensation) reactions between flavonoids.
 The polymers may include up to 50 monomer
units.
 On treatment with acids or enzymes condensed
tannins are converted into red insoluble
compounds known as phlobaphenes.
Phlobaphenes give the characteristic red colour to
many drugs such as red cinnamon bark.
 Examples of drugs containing Condensed
tannins:
Some drugs (e.g. tea, hamamelis leaves and hamamelis
bark) contain both hydrolysable and condensed tannins.
The following are rich in condensed tannins.
(1) Barks: cinnamon, wild cherry, cinchona, willow, acacia, oak
and hamamelis
(2) Roots and rhizomes: krameria (rhatany) and male fern
(3) Flowers: lime and hawthorn
(4) Seeds: cocoa, guarana, and kola
(5) Leaves: hamamelis, hawthorn and tea, especially green tea
(6) Extracts and dried juices: catechu, acacia and mangrove
cutches
Properties and tests of tannins
 Tannins are soluble in water, dilute alkalis, alcohol,
glycerol and acetone, but generally only sparingly
soluble in other organic solvents.
 Solutions precipitate heavy metals, alkaloids, glycosides
and gelatin.
 With ferric salts, gallitannins and ellagitannins give blue-
black precipitates and condensed tannins brownish-green
ones. If a very dilute ferric chloride solution is gradually
added to an aqueous extract of hamamelis leaves (which
contains both types of tannin), a blue colour is produced
which changes to olive-green as more ferric chloride is
added. Other useful tests are the following:
1. Goldbeater's skin test
Soak a small piece of goldbeater's skin in 2%
hydrochloric acid; rinse with distilled water and
place in the solution to be tested for 5 min. Wash
with distilled water and transfer to a 1% solution
of ferrous sulphate. A brown or black colour on
the skin denotes the presence of tannins.
Goldbeater's skin is a membrane prepared from
the intestine of the ox and behaves similarly to
an untanned hide.
2. Gelatin test
Solutions of tannins (about 0.5-1 %) precipitate a
1% solution of gelatin containing 10% sodium
chloride. Gallic acid and other pseudotannins
also precipitate gelatin if the solutions are
sufficiently concentrated.
3. Phenazone test
4. Test for catechin
5. Test for chlorogenic acid
Medicinal and biological properties
The applications of tannin-containing drugs are
limited, and result from their affinity for proteins.
 Tannin-containing drugs will precipitate protein
and have been used traditionally as styptics and
internally for the protection of inflamed surfaces
of mouth and throat.
 They act as antidiarrhoeals and have been
employed as antidotes in poisoning by heavy
metals, alkaloids and glycosides.
sumac