Important Phenols

in Pharmacy:
Simple Phenolics

Tannins
Lignins
GLYCOSIDES

Glycosides
a compound that yield one or more sugar
among the product of hydrolysis.

non-sugar
(genin)

glycosidic
linkage

sugar
(glycone)

General Methods of
Isolation
Destruction of hydrolyzing enzymes
De-fating
Extraction
Concentrate the extractives

General Methods of
Isolation
Add water

Filter

Add lead acetate

Purified glycosides
(crystallization)

Aqueous
Extract

Treat with
Organic solvent

Classification of Glycosides
based on aglycone
Alcoholic or

Cyanogenic

phenolic
Aldehyde
Alkaloidal
Anthracene or
anthraquinone
Chromone
Coumarin

Flavonoidal

Glucosinolates/

isothiocyanates
(sulfur containing)
Napthoquinone
Steroidal (cardiac
glycosides)

Classification and
Nomenclature
1. According to the type of glycosidic

linkage
2. According to the chemical group of
the aglycone involved into the acetal
union
3. According to the nature of the simple
sugar component of the glycoside
4. According to the number of the
monosaccharides in the sugar moiety

O-Glycoside
CH2 OH

CH2OH

O-C6 H11 O5

OH

C6 H12 O6 +

-H2O

Glycosidic linkage

S ugar

C-Glycoside

Salicin

N-Glycoside

S-Glycoside
Glycosidic linkage
SH

C6H12O6
Sugar

+ CH2

CH

CH2

C
CH2
N

CH

CH2

OS O3 K

Sinigrin

C6 H11 O5

OS O3 K

Classification and
Nomenclature
5. According to the physiological or

pharmacological activity/therapeutic
classification.
6. According to the correlation to the
parent natural glycoside
Amygdalin

Amygdalin
hydrolase

Prunasin
hydrolase

Prunasin

R-mandelonitrile

7. According to the plant families

Physical and Chemical

Properties
Physical Properties
Most glycosides are water soluble

and SOLUBLE in alcohols.

Insoluble or less soluble in non
polar organic solvents.
More sugar units in a glycoside
lead to more soluble in polar
solvents.

Physical and Chemical

Properties
Chemical Properties
Glycosides do not reduce

Fehling's solution, but when

susceptible to hydrolysis give reducing
sugars (C-glycosides are exceptions).

Stability and Hydrolytic

Cleavage
Acid hydrolysis: all glycosides are
hydrolyzable by acids.
Acetal linkage is more unstable between two
individual sugars within the molecule
Glycosides containing 2-deoxy sugars are
more unstable even at room temperature.
C-glycosides are very stable (need oxidative
hydrolysis).

Alkali hydrolysis:
Strong alkali or mild alkali

Stability and Hydrolytic

Cleavage
Enzymatic hydrolysis:
Specific for each glycoside; but same

enzyme is capable to hydrolyze different

glycosides.
Emulsin is found to hydrolysed most glycoside linkages;
Maltase and invertase are glycosidases.

Stability and Hydrolytic

Cleavage
Enzymatic hydrolysis:

Identification Test
Unsaturated Steroidal and

triterpenoidal glycosides
Liebermanns Burchard Test
Result: green color/violet-blue
Salkowskis test: yellow color
Antimony chloride test: pink solution

upon heating
Trichloroacetic acid test: colored ppt
Tetranitromethane test: yellow solution
Zimmermann test: violet color

Identification Test
Chemical tests for cardiac

glycosides:
Keller killiani test (presence of
digitoxose: reddish brown layer which
turns bluish green)
Lejal/Legal test: pink color
Baljet test: yellow to orange color
Kedde test: pink color

Identification Test
Anthraquinone glycosides:
+ Borntragers / Modified

borntragers (C-type)
Result: Reddish coloration with alkali

Identification Test
Coumarin glycosides
Ferric chloride test: deep green which

turns to yellow upon addition of conc.

Nitric acid
Fluorescence test: blue-green
fluorescence
Leucoanthocyanins
Bate Smith and Metcalf Test Method
Strong-red or violet

Identification Test
Cyanogenetic glycosides - hydrolysis

hydrocyanic acid
tested by change Sodium picrate paper

(yellow) to red color.

Sulfur containing glycosides
give black precipitate of silver sulfate upon
treatment with AgNO3 solution.

Saponin Glycosides
Froth Test
Agar Cup Method Hemolytic Test

Identification Test
Flavonoidal glycosides:
Characteristic color with, NH4OH, AlCl3, FeCl3
Alkaline reagent test (ammonia test)
Shinoda test
Vanillin HCl test

Wilstatter Test aka Cyanidin Test

With conc. acid and Mg produces colors ranging
from orange to red, crimson and magenta and
occasionally to green or blue indicates the
presence of benzo-pyrone nucleus.

Special Test based on the

chemical structure
Determination of the glycosidic

linkages:
Use of and glycosidases
Optical activity

Color reactions based on the sugar:

Keller Killiani (Test for 2-deoxysugars)
Glacial acetic acid containing + FeCl3 + H2SO4 brown

ring free from red (acetic acid = blue).

2- Xanthydrol:
xanthydrol in glacial acetic containing 1% HCl + glycoside

[heat] red color.

Medicinal importance of
glycosides
1. Cardiac drugs: cardiotonic glycosides

e.g: digitalis glycosides, strophanthus, squill

2. Laxatives: anthraquinone glycosides
e.g: senna, aloes, rhubarb, cascara, frangula
3. Counter-irritants: thioglycosides and
their hydrolytic products e.g:
allylisothiocyanate
4. Analgesics: methyl salicylate a hydrolytic
product of gaultherin

Medicinal importance of
glycosides
5. Anti rheumatic: e.g: salicin.
6. Some glycosides are claimed to reduce

the

capillary fragility: e.g: flavonoidal

glycosides, rutin, hesperidin
7. Anti-inflammatory: the glycoside
glycyrrhizin has a demulcent, expectorant and
antispasmodic action
8. More recently as an anticancer

agent e.g.,

amygdalin known in the U.S. as Laetrile

Simple Phenolic
Compounds
Catechol or _______
Present in Kola seeds and leaves of

Gaultheria spp.
The derivatives are the urushiol
phenols of the poison oak and
poison ivy
Resorcinol or ________
Constitute the narcotic principle of
cannabis
Hydroquinone or _______

Simple Phenolic
Compounds
Other phenolics includes:
Eugenol phenolic phenylpropane
Vanillin phenolic aldehydes
Salicylic acid
Ferulic acid

Caffeic acid
Study Table 21.1 page 221

Simple Phenolic
Compounds
CN: Meadowsweet

Use/s:

SN: Filipendula

Diuretic

ulmaria; Spirea ulmaria

FN: Rosaceae
Constituents:

Traditionally used as

Salicylaldehyde
Methylsalicylate
Benzaldehyde
Benzyl alcohol

anti-inflammatory,
astringent and
stomachic agent

Simple Phenolic
Compounds
Methyl salicylate
Sources:

Gaultheria procumbens
Gaultheria fragrantissima
Betula lenta

Use/s:
Counterirritant
Soothing effect
aka _______________

Simple Phenolic
Compounds
Willow bark
Salix purpurea (purple)
S. daphnoides
S. fragillis (crack)

Constituents:
Salicin phenolic glycosides
Condensed tannins
Isoquercitin, chalcone

Uses:
Anti-inflammatory in the tx of

rheumatism, arthritis and

muscular pains.

Simple Phenolic
Compounds
Black haw bark
Viburnum prunifolium
FN: Caprifoliaceae

Constituents:
0.2% Salicin
Tannins/ and resins
Reported use/s:
Tx of dysmenorrhea
Abortifacient
Tx for asthma

Simple Phenolic
Compounds
Hops: Humulus lupulus L.
FN: Caprofoliaceae
Constituents:
Humulene
Phloroglucinol derivatives
humulone, lupulone
Xanthohumol
Use/s:
Anti estrogen
Anti oxidant
Mild sedative

Simple Phenolic
Compounds
Male Fern (Filix Mas)
Dryopteris filix-mas

FN: Polypodiaceae
Intact plant possess an

internal green color.

Constituent:
Phloroglucinol
derivatives
Use:
Anthelmintic(tapeworm)

Simple Phenolic
Compounds

Kamala

Mallotus philippinensis
FN: Euphorbiaceae

Constituents:
Phloroglucinol

derivative like rottlerin

and isorottlerin
Use:
Anthelmintic

Simple Phenolic
Compounds

Wood tar

(Stockholm tar)
FN: Pinaceae
Characteristics:
Prepared by

Constituents:
Cresols, Methyl cresols
Cathecol/pyrocatechin
Guaiacol (methyl

cathecol)
destructive distillation
Benzene
(methanol, acetone).
Toluene
Blackish semi liquid
Characteristics odor
Use:
Tx psoriasis

Simple Phenolic
Compounds
Coal tar
Prepared by destructive

distillation of bituminous coal

Characteristics:
Black viscous liquid
Forms alkaline solution with
water.
Petroleum spirit extract has a
blue fluorescence enhanced by
UV light
Use:
Treatment of psoriasis

Simple Phenolic
Compounds
Vanilla (Vanilla Pods) Vanillin BP
Vanilla fragrans

Aldehyde

V. planifolia

corresponding to
methylprotocathechuic acid
Uses:

V. tahitensis
V. pompona

FN: Orchidaceae

Constituents:
Glucovanillin
(vanilloside),
glucovanillic alcohol

Flavoring agents
Coloring agents

Simple Phenolic
Compounds
Bearberry (Uva ursi)
Arctostaphylos uva-ursi
FN: Ericaceae
Constituent:
Arbutin, methyl arbutin, quercitin,
gallic acid, elagic acid, and ursolic acid
Use/s:
Urinary Antiseptic
Diuretic (due to hydroquinone)
Astringent

Simple Phenolic
Compounds

Simple Phenolic
Compounds
Capsicum (Red

Peppers)
Capsicum annuum
C. frutescens
FN: Solanaceae
Constituents:
Capsaicin
Red carotenoids

capsanthin and
capsorubin.
Fixed oils

Use/s:
Condiments cayenne

pepper
Internally as atonic
dyspepsia
Externally as a counterirritant (plaster,
ointment)
Used as a relief for
rheumatism

Coumarin Glycosides
Derivative of ________
These includes:
(1)
(2)
(3)
(4)
Umbelliferone [7-hydroxy coumarin] is the

lactone of umbellic acid which occurs both in

the free state and in the form of glycosides in
some resins of the Umbelliferae

Coumarin Glycosides
In ammoniacal solution, these compound produce

blue, blue-green or violet fluorescence (conjugated

double bond system).

Study Table 21.2, pg 233

Coumarin Glycosides
Furanocoumarins
responsible for the
effect on the drug
availability.
WHY???

Coumarin Glycosides
Angelica Roots
Angelica archangelica L.
FN: Umbelliferae
Constituents:
Furanocoumarins
Bergapten
Angelicin
Use/s:
Archangelicin
Potent coronary
Apterin
vasodilator effects
Marmesin and psoralen Calcium antagonist

Coumarin Glycosides

Coumarin Glycosides
Melilot
Melilotus officinalis
FN: Leguminosae

Constituent/s:
Coumarin derivatives
Melilotic acid
Caffeic acid
o-Coumaric acid
new-mown hay odor

Coumarin Glycosides
Tonco seed
Dipteryx odorata and D.

oppositifolia
Family Name: Leguminosae
Constituents:
1 3% coumarin
Use/s:
Tobacco manufacture and

perfumery

Coumarin Glycosides
Celery fruit
Apium graveolens
Family Name:
Umbelliferae
Constituent/s:
Coumarin and phenolic glycosides
Furanocoumarins
Use/s:
Tx of rheumatic disease

Other Lactone
Cantharides/Blistering

Flies/Spanish flies
Cantharis vesicatoria Family

Meloidae
Constituent: Cantharidin
USE: Vesicating agents, irritants
Dicumarol
MOA: competitive inhibitor
of Vitamin K, preventing the
formation of prothrombin
USE: Anticoagulant

Anthraquinone
Glycoside

Stimulant cathartic
exert their action by increasing
the tone of the smooth muscle in
the wall of the colon and
stimulate the secretion of water
and electrolyte into the large
intestine.
Stimulant laxative
habit forming, may result to
laxative dependence and loss of
normal bowel function.

Anthraquinone
Glycoside
Anthraquinone

Anthrone

Anthranol

O
1

10

4H

OH

10

4
H

2H

8
7

10

OH

Oxanthrone

Types of
Anthraquinone Glycosides
O-glycosides where the aglycone moiety is 1,8

dihydroxyanthraquinone derivatives

Types of
Anthraquinone Glycosides
O-glycoside where the aglycone moiety partially

reduced 1,8 dihydroxy anthraquinone, e.g.,

Gl
Oxanthrone-type.
OH
H
7

O
9

OH

10
5

4
O

Emodin-oxanthrone-9-glucoside

Types of
Anthraquinone Glycosides
C-glycoside where the aglycone structure

(anthrone derivative)
O

OH
7

6
5

OH

10

C6 H11 O5
Barbaloin

CH2 OH

Types of
Anthraquinone Glycosides
O-glycosides where

the aglycone moiety is

di-anthrone derivative
(a dimer) e.g.,
Sennosides where there
is C-C bridge between
the anthranol units.
Sennoside A&B

Official anthraquinone
drugs in B.P and U.S.P.:
Senna leaf & senna fruit (pod)
Aloes

Cascara tablets, elixir, dry exract, liquid

extract
Rhubarb powdered, tincture
Danthrone
Frangula bark

Cascara Sagrada
Rhamnus purshianus Decandolle
FN: Rhamnaceae
aka sacred bark
Cathartic used in the correction of habitual
constipation;
Obtained by percolation and evaporation;
Bitter taste and activity may be reduce by treating
extract with alkaline earth or Magnesium oxide
Casanthranol purified, watersoluble mixture

of anthranol glycosides extracted from cascara

sagrada

Cascara Sagrada

Cascaroside A & B: optical isomers of barbaloin

Cascaroside C & D: optical isomers of chrysaloin

Cascara Sagrada
Two aloins (secondary glycosides):
Barbaloin derived from (C-10-C-glycoside) of
aloe-emodin anthrone
Chrysaloin derived from (C-10-C-glycoside)
of chrysophanol anthrone.

Cascara Sagrada
O- glycosides:
derived from emodin, emodine oxanthrone, aloe
emodin and chrysophanol.

Frangula (Buckthorn
Bark)
Rhamnus frangula Linne
FN: Rhamnaceae
Constituents: Frangulins A & B,

glucofrangulins A & B
It should be aged 1 year to reduce harsh
action of the glycosides to a milder form
Frangulin (frangula emodin rhamnoside)
Glucofrangulin (frangula emodin
glucorhamnoside)

Frangula (Buckthorn
Bark)

Aloe or Aloes
Aloe barbadensis Miller

(Curacao aloe)
Aloe ferox Miller (Cape aloe)
Aloe africana Miller
Aloe spicata Baker.
FN: Liliaceae
Reddish black or brownish
black with nauseating and
bitter taste and disagreeable
characteristic odor.

Aloe or Aloes
Dried latex of the leaves of Aloe

barbadensis
Constituent/s:
Aloin A (Barbaloin)
Aloin B (Isobarbaloin)
A pharmaceutic aid for Compound
Benzoin Tincture
Use: Cathartic

Rhubarb aka Rheum/

Chinese Rhubarb
Rheum officinale Baillon
Rheum plamatum Linne

FN: Polygonaceae
Constituent:
Rhein anthrones
Use:
Drastic cathartic action

(purgative)

Indian rhubarb aka

Himalayan rhubarb
Rheum emodi Wallion
Rheum webbianum Royle
FN: Polygonaceae
Constituents:
Rhein, rhein anthrone, chrysophanol and

aloe emodin.
Dianthrones of heteroanthrone types are
palmidin A,B,C, rheidins, sennosides A&B
and their oxalate esters (sennosides E&F).

Indian rhubarb aka

Himalayan rhubarb
Tannins present in

rhubarb makes the drug

constipating.
Small doses: no purgative
action but acts as
intestinal astringent,
Large doses: purgation

Senna/Senna leaves
Cassia acutifolia Delile Alexandria or

Cassia Senna
Cassia angustifolia Vahl Tinnevelly
Senna
FN: Fabaceae
Constituent:
Sennosides A and B rhein dianthrone
(Sennidin A+B)
Use/s: Purgative (liquid extract, elixir or as
tablets prepared from dry extract)

Senna/Senna leaves
Dianthrone
Only compound which is used to
some extent in current medicine
OH
Used as standard in colorimetric
assays of anthraquinone
glycosides.

Some of these synthetic

compounds act too drastically and

also caused kidney damage.

Anthrone

OH

Senna/Senna leaves
Homo-dianthrones vs. hetero-

dianthrones
Gl

Gl

OH

7
7

10
5

10

6
6

OH

COOH

H
H

COOH
COOH

Gl

CH2 OH

OH

Sennosides A &B

Gl

OH

Sennoside C&D

Cassia pods
Dried ripe fruits of Cassia fistula
Family Name: Leguminosae
Constituents:

Rhein, ennidins and sennosides A

and B (leaves)
Barbaloin, rhein and
leucoanthocyanidin (heartwood)
Use/s:
Laxative

Chrysarobin
A mixture of araroba or goa powder

and extracted with hot benezene

Araroba (Andira araroba)
Family name: Leguminosae
Constituent/s:
Chrysophanol anthranol
Use/s:
Formerly used for skin disease

Madder
From the root of Rubia tinctorum
Family: Rubiaceae
Constituents and use:
Ruberythic acid that yields

alizarin and primeverose upon

hydrolysis
Used as a dye but replaced by
synthetic dyes

St. Johns Wort

Hypericum perforatum
Family: Clusiaceae
Constituent/s:

Hypericin and pseudohypericin

Iso-hypericin, emodin-anthrone
Prenylated phloroglucinol derivatives
Use/s:
Anti-depressant

Tagged as natures Prozac

Cochineal
From dried female insect Dactylopius

coccus, egg and larvae

Constituent:
Carminic acid (10%)
Use/s:
Colorant/ indicator

Remember the following

for anthraquinone
glycosides:
Primary glycosides: more active than

aloins;
Free anthraquinone: little purgative
activity
C-C glycosides of aloins: very resistant
to hydrolysis and are not easily
hydrolyzed

SAR of Anthraquinone
Glycosides
Glycosylation
Hydroxylation (C-1, C-8)
Oxidation (C-9, C-10)

SAR of Anthraquinone
Glycosides
The nature of substances at C-3:
Derivative with CH2OH (as in aloe
emodin) are more active than those with
CH3 substitution. The latter more active
than derivative with COOH substitution at
C-3.
Anthraquinone glycosides containing a
dimer is more active than a monomer.

SAR of Anthraquinone
Glycosides
Effect of storage on the active of

anthracene glycosides:
Long storage bring oxidation of

anthranols and anthrones to give the less

active anthraquinones.
Anthraquinone glycosides do not
cause any griping action (like anthranol
and anthone), thus no antispasmodic such
as belladonna is prescribed with them.

Properties of
Anthraquinone derivatives
Extracted and hydrolyzed by boiling with

acids.
Aglycones are extracted from the acidic
solution with ether or benzene.
Upon shaking the ether or benzene layer with

aqueous alkali or ammonia solution, the

aqueous layer assumes a deep red color, because
of the formation of anthraquinone salts.

Naphthoquinone
Glycosides
Produced by higher plants, fungi

and actinomycetes
Use/s:
Fungicidal, antibacterial, insecticides,

phytotoxic, cytostatic and anticarcinogenic

Juglans regia
FN: Juglandaceae
4-D-glucoside of hydroguglone (leaves of

walnut tree)

Naphthoquinone
Glycosides
Synthesized via:
Acetate and malonate pathway

Plumbagin (Plumbago spp)

Shikimate/Succinyl CoA combined
pathway Lawsone
Shikimate/Mevalonate combined
pathway - Alkannin

Naphthoquinone
Glycosides
Henna
Lawsonia inermis
FN: Lythraceae

Constituent/s:
Lawsone (hydroxynaphthoquinone)

colorant
Isoplumbagin anti-inflammatory
Use/s:
hair dye
astringent (stem-bark)
Tx for jaundice, enlargement of the liver

and spleen
Tx for skin diseases

Naphthoquinone
Glycosides
Lithospermums spp. (Family Name:

Boraginaceae)
Reported hormonal activities
Shikonin naphthoquinone derivative
Scyllitol cyclitol
Cyanoglucoside lithospermocide
Use Purple roots tx burns, inflammation,
wounds and ulcers
Lithospermum arvense (L. rudelare) oral
contraceptive agents, suppress estrus cycle.

Naphthoquinone
Glycosides
Alkana root

(Alkanet/Anchusae radix)
Alkanna tinctoria
FN:Boraginaceae
Constituent & use:
Alkannin - Red

naphthoquinones

Chromones and
xanthones
Structural derivative of benzo- pyrone
Chromones: iso form of coumarins ex:

eugenin from ___________.

Xanthones came from the family _______,
________, _______ and ________.
Reported use/s:
Anti-inflammatory
CNS stimulant/depressant
What is the complex xanthones present on
mycotoxin pigment of ergot?

Flavonoidal Glycosides
Largest group of naturally

occurring phenols
It includes anthocyanin and
leucoanthocyanin
Flavonoidals constitute the
majority of the
colored plant pigments
Many flavonoidal compounds
present as a glycosidic or as a
free forms.

Flavone nucleus

Neoflavonoid nucleus

Flavonoidal Glycosides
Derived from flavan (2-phenyl-benzopyran), have a

basic C-15 skeleton

Classes/types:
Flavones (2-phenyl chromones)
Isoflavones (3-phenyl chromones)
Flavonols
flavanones(true flavanoids) 2,3-dihydro
derivatives of flavones
Anthocyanidins
Chalcones
Aurones

Flavonoidal Glycosides
Chalcones

have no central pyrone ring

not true flavonoidal compounds.
chemically phenyl-styryl ketone, or

benzylidene acetophenone
Aurones
are oxidized form, obtained by
enzymatic oxidation.
have five membered ring
(instead of the central pyrone
ring)

Properties of Flavonoids
Dissolve in alkalis give intense yellow color

solution, on the addition of acid become

colorless
Exhibit strong fluorescence under UV light
Soluble in water and alcohol.
Ethylacetate is the solvent of choice for
the extraction of flavonoids from aqueous
solution

Flavonoidal Glycosides
Hesperidin
Occurs in various citrus fruits
Found in the root bark of rasaceous plants
Rutin Rutaceae Vitamin P

Flavonoidal Glycosides
Buchu leaves
Barosma crenulata
FN: Rutaceae
Constituent/s:
Diosmin - flavone

glycoside
Use/s:
Diuretic and diaphoretic
action

Flavonoidal Glycosides
OH
Rha-Gl

A
OH
O

Upon hydrolysis, diosmin yields _______,

________and ________.

OCH3

Flavonoidal Glycosides
Rutin and quercetrin (flavonol glycosides)
Rutin occurs in the leaves of buckwheat.
It is the 3-rhamnoglucoside (called rutinose) of

the genin quercitin.

It gives on hydrolysis the aglycone (quercitin)
beside one molecule of glucose, and one molecule
of rhamnose.
Rutin is used to decrease capillary fragility;
It is a biflavonoids that plays a true vitamin

function.

Flavonoidal Glycosides
Quercitrin is quercitin 3-O-

rhamnoside.
Quercus tinctoria bark
Quercitrin yield upon acid
hydrolysis rhamnose and
quercetin.
The aglycone quercetin occurs in
bearberry leaves and has a diuretic action of
the leaves.

Flavonoidal Glycosides
OH
O

HO

A
OR
OH
O

Quercetin: R=H
Quercetrin: R= rhamnosyl
Rutin:

R=rutinosyl

OH

Flavonoidal Glycosides
Hesperidin

It is the main flavonoidal glycoside of citrus fruits.

Upon hydrolysis by acid, hesperidin gives

rhamnose, glucose and hesperitin.

Uses:
Hesperidin appears to be identical to vitamin P

(citrin).
It is necessary for absorption and retention of
vitamin C that lead to decrease capillary fragility.
Decrease CVD and HTN.

Flavonoidal Glycosides
OH

A
OH
O

Hesperitin R:H
Hesperidin R:rutinosyl

OCH3

Flavonoidal Glycosides
Increase capillary resistance and decrease

vitamins C & P deficiency.

They are recommended in the treatment of
thrombopenia (blood coagulation).
They are reported of value in the treatment
of influenza, when given with ascorbic acid.

Flavonoidal Glycosides
O

HO

O
O

OH

O
OH

Genistein show significant

estrogenic activity.

Rotenoids
employed as insecticide

The leaves and fruits of Silybum

marianum family
Compositae contain
silymarin.
O

OH

A
OH
OH

OH
OCH3

Silybin

OH

Silymarin
Effective lipotropic and hepato-protective

therapy;
It is a free radical scavenger (anti-oxidant)
Supportive treatment of acute and chronic
alcoholic poisoning and toxin induce hepatitis;
It is used for treatment of liver cirrhosis caused
by plant toxins (mushroom, amanita), silymarin
IV
Available in the market in the form of tablets,
effervescent granules.
Trade name: Legalon

Synthetic Flavonoids
O

N
O

A
CH3
O

Uses:

Flavoxate

To remove pain (anti-spasmodic) and anti-

inflammatory of the genitor urinary tract

Agnus castus
Vitex agnus castus
FN: Verbenaceae
Constituent/s:

Glycosides
Flavonoids

Fixed oils
Volatile oil
Use/s:

Topical tx for skin diseases

Birch
Betula pendula
FN: Betulaceae
Constituent/s:
Glycosides
Flavonoids
Fixed oils
Anthocyanidin
Use/s:
Tx of melanoma

Calendula/Marigold
Calendula officinalis
FN: Compositae
Constituent/s:
Flavonoids
Triterpenoids
Essential oils

Several polysaccharide
Use/s:
Tx of GIT disorder

Tx of minor wounds and rashes

Elder flower
Sambucus nigra
FN: Caprofoliaceae
Constituent/s:
Semi-solid volatile oil
Flavonoids
Triterpenes
Sitosterol
Use/s:
Tx of common cold
Antipyretic
Diaphoretic

Horsetail
Equisetum arvense
FN: Equisetaceae
Constituent/s:
Flavonoids
Phytosterols
Phenolic acid
Alkaloids
Use/s:
Diuretic
Hemostatic agent
Astringent

Java Tea
Orthosiphon staminus

FN: Laminaceae
Constituent/s:
Flavonoids
Diterpene
Phystosterol
Use/s:
Anti-hypertensive agent
Anti-diabetic

Tx of several GIT

disorder

Lime flower
Tilia odorata
Tiliaceae
Constituent/s:
Fixed oils
Flavonoids
Phenolic acid
Mucilages (gums)
Use/s:
Tx for headache
Anti-spasmodic
Indigestion
Nerve tonic

Motherwort
Leonorus cardiaca
FN: Laminaceae/Labiatae
Constituent/s:
Stachydrine
Flavonoids
Irioids
Tannins
Triterpenoids
Use/s:
Tx dysmenorrhea
CDV disease
Nervous tension

Olives leaves
Olea europea
Oleaceae
Constituent/s:

Rutin
Oleorutin
Olive oil

Use/s:
Tranquilizer
Anti-septic
Astringent

Passiflora
Passiflora incarnata

Passifloraceae
Constituent/s:
Flavonoids
Alkaloids
Volatile oils
Cyanogenetic

glycosides
Use/s:
Anxiolytic

Spiny Restharrow
Ononis spinosa
Leguminosae/Papilionaceae
Constituent/s:
Isoflavones
Tannins
Lectins
Triterpenoids
Volatile oils
Use/s:
Diuretic
Anti-inflammatory
Tx for the removal of kidney and
gallstones

Buckwheat
Fagopyrum esculentum
Polygonaceae
Constituent/s:

Rutin
Use/s:
Tx of varicose veins,

childbalins
Retinal bleeding

Anthocyanidin and its

Glycoside
Anthocyanidins are flavonoids

structurally related to flavones.

Anthocyanins glycosides of
anthocyanidins
Etiology: antho flower & kyanos blue
Anthocyanidins and its glycosides
responsible for the permanent blue, purple,

violet, mauve, and red color of flower, fruits

and leaves of higher plants
aka __________

Anthocyanidin and its

Glycoside
Anthocyanidin

Occurrence of
glycosides

Pelargonidin

Flowers of Pelargonium and

pomengranate
Cornflowers, red poppies,
Rosa spp., cocoa and cherries
Peonyl (Ranunculaceae)
Delphinium and Viola spp.
Petunia spp.
Malva spp.

Cyanidin

Peonidin
Delphinidin
Petunidin
Malvidin

Anthocyanidin and its

Glycoside
Cyanidin
chloride
is an example of
anthocyanidins

Leucoanthocyanin
Upon hydrolysis yields sugar and

leucoanthocyanidin
Plant materials boiled with diluted

acids gives intense red or violet color

Lignans and Lignins

Dimeric compounds formed essentially by the

union of 2 molecules of phenylpropene derivatives.

Optically active; arise by stereospecific, reductive
coupling between the middle carbons of the sidechain monomer
Podopyllum spp formed by 2 molecules of
coniferyl alcohol and corresponding acid.
Neolignans - derived same as lignans, but the
C6-C3 moieties are linked head to tail or head to
head and not through -carbons.

Lignans and Lignins

Source

Lignans

Type of lignans

Guaiacum officinale

-Guaiaconic acid A furano type lignans

Myristica fragrans
(Nutmeg)

Macelignans

A dibenzylbutane-type

Piper cubeba (Tailed pepper) (-)-Cubebin

A tetrahydrofuran-type

Podophyllum spp.

Podophyllotoxin

Aryltetralin type

Schinsandra chinensis

Wuweizisu C

Dibenzocyclooctadiene
type

Silybum marianum

Silybin

Flavonolignans

Urtica dioica (Nettle)

Neo-olivil
derivative

Tetrahydrofuran

Viscum album (Mistletoe)

Eleutheroside E

Tetrahydrofuran

Zanthoxylum clava-hercules (+)-Asarinin

Tetrahydrofuran

Flavono-lignans
Coupling of a flavonoid moiety with hemi-lignan

molecule by oxidative coupling.

O

OH

OR

OH
+
OH

OH

Hemi-lignan moiety

Flavonoid moiety

OH

O
OH

OH
OCH3

OH

Flavonolignan

Saponin Glycosides
Forms colloidal solution in water that foams

upon shaking, colorless and optically active.

Have bitter, acrid taste; irritating to the
mucous membrane; destroy red blood cell
by hemolysis and are toxic especially to
cold-blooded animals
Sapotoxin- poisinous saponin used for
controlling schistosomiasis snails.
2 types of sapogenin
Steroidal- in monocot families
Triterpenoidal- in dicot families

Saponin Glycosides
Saponins are a group of amorphous colloidal

glycosides which is widely distributed in the

higher plants.
They are excellent emulsifying agents
(modify surface tension).
Formerly used as detergents to replace soap
(e.g., quillaia).
NOTE: very difficult to purify

Saponin Glycosides
Chemically:
Saponins are classified according to the
genin part into:
Steroidal type C25.
Triterpinoidal type C30.
Both types of saponins have the glycosidic
linkage at position 3.

Saponin Glycosides
O

O
COOH
R2
HO

HO
R1
Diosgenin
Quillaic acid: R1=CHO, R=OH
Olianolic acid R1=CH3, R2=H

Medicinal importance of
saponins
The steroidal saponins are structurally

related to modern synthetic compounds

that have a therapeutic significance, such
as adrenocortecoids and the sex hormones.
They are a suitable precursors in the
partial synthesis of these hormones, e.g.,
Diosgenin (sapogenins) isolated from the
rhizome of Dioscoria species.

CH3
OH
O

CO
OH

Testosterone

Progesterone
O

CH2 OH

HO

Cortisone
Diosgenin

CO
OH

Medicinal importance of
saponins
Saponins increase the rate of absorption of

many pharmacological active substances

(e.g., cardiac glycosides).
Many saponin-containing drugs are used as
expectorants (e.g., Ipecac, Senaga and
liquorice) as their contents of saponins
stimulate bronchial secretion and also
activate the cilliary epithelium of the
bronchi.

Medicinal importance of
saponins
The triterpenoidal saponin glycoside,

glycyrrhizin, is the main sweet principle

of liquorice it is also used demulcent,
expectorant and antispasmodic action.
It is calcium and potassium salts of
glycyrrhizic acid, which in tern is the
diglucuronic acid glycoside of
glycyrrhitinic acid.

COOH

Glucuronic-glucuronic

B-Glycyrrhitinic
Glycyrrhizic acid

Glycyrrhizin =Ca, K

Saponins drugs Officially

B.P and U.S.P:
Quillaia bark: used as

emulsifier

Liquorice root: used as

flavoring agent and

expectorant

Glycyrrhiza (Licorice
root)
Glycyrrhiza glabra Linne (Fabaceae)
Glycyrrhizin- 50x as sweet as sugar but once

converted to its algyone glycyrrhetic acid its

loses its sweetness
Use/s:
Demulcent, expectorant, increase fluid
retention.
Glycyrrhetic acid- used in dermatological
practice as anti inflammatory.
Licorice root extract- use in the tx of peptic ulcer
& Addisons disease.

Ginseng
Panax quinquefolius Linne (American ginseng)
P. ginseng (Asian ginseng)
Constituent/s:
Ginsenosides, panaxoside and

chikusetsusaponins
Use/s:
Tonic, stimulant, diuretic and carminative,

adaptogenic (anti stress) in the Orient-anemia,

diabetes, insomnia, neurasthenia, gastritis and
sexual impotence

Ginseng

Asian ginseng

American ginseng

Saponin Glycosides
Sarsaparilla
Smilax aristolochiaefolia
S. regelii
Constituent/s:
Sarsaponin, smilagen

Use: flavoring agent

Dioscorea
Dioscin- diosgenin

Cyanogenic Glycosides
aka __________

Yields ______ upon hydrolysis, benzaldehyde and

sugars
Plant containing these glycosides are toxic
The aglycone part is a derivative of
benzaldehyde cyanohydrin of a carbonyl
compound (condensation product of HCN with an
aldehyde or ketone);
Detected with Guignards reagent gives yellow
to maroon;
Picrate paper test brown to brick red color

Cyanogenic Glycosides
O

OH
HCN

S ugars

CH
H

CN

Benzaldehyde

Mandilonitrile

CH3
C
CH3

Acetone

Mandilonitrile glycosides

HCN

CH3

OH
C

CH3

O-Gl

CH3
S ugars

CN

Acetone cyanohydrin

C
CH3

CN

Linamarin

Amygdalin (D-Mandelonitrile
gentiobioside)
Amygdalin is the most widely distributed

cyanophore glycoside.
Amygdalin - in Laetrile or vitamin B17
claimed to be anticancer and control sickle
cell anemia.
It occurs in several Prunus species, and is

obtained from bitter almonds (Prunus

amygdalus var. amara Family
Rosaceae).

CN
C
O
O
6
CH2 OH

1
H

5
3

6
CH2
5
3

O
2

4
4

CN

Amygdalin

C
O

CH2 OH
5
3
4

O
2

Prunasin

Cyanogenic Glycosides
Acid hydrolysis of amygdalin split two molecules

of glucose and one molecule of mandelonitrile. The

latter decomposes spontaneously to form
benzaldehyde and HCN.
Different enzymes act upon amygdalin in different
ways:
Amygdalase

Gl-Gl-O

CN

Prunase

Glocose + Prunasin

Prunase

Gentiobiose + Benzaldehyde + HCN

H
Amygdalin

Emulsin
or acid

Glucose + Benzaldehyde + HCN

Glucose + HCN +Benzaldehyde

Wild cherry
Wild black cherry tree
Prunus virginiana
Prunus serotina Ehrhart (Rosaceae)
Constituent:
Prunasin- formed by partial hydrolysis of
amygdalin;
Prunase, p-coumaric acid
Use/s:
Sedative, reported

anticancer

Apricot pits
Prunus armeniaca linne.

(Rosaceae)
Contains amygdalin and
emulsin
Emulsin- an enzyme that
hydrolyzes glycoside
releasing toxic cyanides
Not use for tx cancer
because of its potential
danger.

Enzymatic hydrolysis of
Amygdalin

Amygdalin

Amygdalin
hydrolase

Prunasin

Prunasin
hydrolase

R-mandelonitrile
Mandelonitrile lyase

Benzaldehyde + HCN + Glucose

Isothiocyanate
Glycosides
A number of plants of the family Cruciferae

yield glycosides containing sulphur.

Hydrolysis of these, yield volatile genins of
thiocyanate structure e.g., mustard oils.
The best known compounds Sinigrin and
Sinalbin, two glycosides occurring in black
mustard and white mustard seed
respectively.

Isothiocyanate
Glycosides
Importance in treatment of cancer:
Mustard: idole 3-carbinol derived
from indolylmethyl glucosinolate
reduce risk of estradiol- linked
mammary cancer
Brocolli: 4-methyl sulfinyl
isothiocyanate induce carcinogenic
protective enzyme.

Isothiocyanate
Glycosides
The glycosides and their

specific enzymes are found in

different cell in the seeds.
They do not interact until
they are brought together by
the distruction of the cell
walls.
The general structure of
thioglycosides is:

S -GL
X

R C
-

N-OS O3

Isothiocyanate
Glycosides

Isothiocyanate
Glycosides
Sinigrin gives upon hydrolysis, glucose,

allylisothiocyanate (volatile oil of

mustard) and potassium acid sulfate.

Isothiocyanate
Glycosides
Hydrolysis of the glycoside sinalbin gives a phenolic

isothiocyanate (Acrinyl isothiocyanate), glucose and

the acid sulphate of a quaternary alkaloid, sinapine.
+

CH3 O

HO

CH-CH-COO-CH2 -CH2 -N

CH3
CH3
CH3

CH3 O
S inalpine cation

Isothiocyanate
Glycosides
Black and white

mustard seeds are

used as rubefacients
and counter
irritants.
These effects are
attributed to their
contents of
thioglycosides.

Isothiocyanate Glycosides/
Glucosinolates
Major role in plants:
Feeding deterrents against insect and mammals
Sulfur- Atom: Brassicaceae
Reported to have anticancer property

indole 3-carbinol derived from

indolylmethyl glucosinolate reduce the
risk of estrogen linked breast cancer.
Methylsulfinyl isothiocyante induce
anticarcinogenic protective enzymes

Black mustard
Sinapis nigra or brown/black

mustard
Brassica nigra Linne Koch
Brassica juncea Linne
czerniaew
Brassicaceae
Constituent/s:
Sinigrin- mustard oil
S=C=N-CH2-CH=CH2

Use/s:
Local irritant & emetic

Hydrolysis of Sinigrin
Sinigrin

myrosinase

Allyl isothiocyanate (mustard oil)

+ glucose + H2SO4

White mustard
Brassica alba Hooker

fillius
FN: Brassicaceae
Sinapis alba
Sinalbin upon hydrolysis

by enzyme Myrosinase
yields p-hydroxybenzyl
isothiocyanate

Garlic (other
organosulfur drugs)
Allium sativum line
Family Name: Liliaceae

Alliin [(+)-S-allyl-L-cysteine sulfoxide]

Comes with contact with enzyme alliinase when
garlic cells are crushed and is converted to
Allicin (diallyl thiosulfate)
Allicin- has potent antibacterial effect, anti
hyperlipidemic and inhibits platelet aggregation.

CH2 OH

Alcohol Glycosides

Gl O

Salicin (salicyl alcohol)

Species of Salix and Populus
Salix pupurea and Salix fragilis
FN: Salicaceae

Salicin is classified as:

Alcoholic glycoside, as it contains free

primary alcoholic group.

A phenolic glycoside, as its aglycone is
phenolic in nature.

Properties of Salicin
Principal commercial source is Salix fragilis.
Salicin is used for many years as a remedy in the

treatment of fever and rheumatism.

Now used as an analgesic-antipyretic in case of
periodic fever.
Better tolerated in the stomach than sodium
salicylate, asprin and other antipyretics and antiinflammatory agents, which have largely displaced
in medical practice.
Salicin is hydrolyzed by the enzyme emulsin into
saligenin (Salicyl alcohol) and glucose.

Properties of Salicin
Acid hydrolysis of salicin gives glucose and a

phenolic ether called saliretin which is a

condensation product of two molecules of
CH OH
saligenin.
2

Gl O

Acid

Enzyme

CH2 OH

CH2 OH

HO

+ Glucose

Saligenin

CH2 OH

Saliretin

+ Glucose

Aldehyde Glycosides
Vanilla aka vanilla bean
Mexican or Bourbon Vanilla- Vanilla planifolia
Andrews (FN: Orchidaceae)
Tahiti Vanilla- Vanilla tahitensis J.W Moore
Constituent/s:
Glucovanillin (avenein) and glucovanillic alcohol
Glucovanillin is a glycosidal constituent of green
vanilla pods.

Aldehyde Glycosides
Vanillin is widely used as a flavoring agent. It may

be obtained from vanilla pod or prepared from

the glycoside coniferin, lignin or from the
phenolic volatile oil constituents eugenol.
CHO

CHO

OCH3

OCH3
O-Gl

Glucovanillin

OH

Vanillin

Vanillin from Coniferin

CH=CH-CH2 OH

CH=CH-CH2 OH

Hydrolysis

CHO

Oxidation

OCH3

OCH3

OCH3

OH

O-Gl

Coniferin

OH

Coniferyl alcohol

Vanillin

Vanillin from Eugenol

CH2 -CH=CH2

CH=CH-CH3

KOH

Oxidation

OCH3
OH

Eugenol

CHO

OCH3
OH

isoeugenol

OCH3
OH

Vanillin

Aldehyde Glycosides
The bulk of vanillin which is produced commercially

is prepared from lignin, which gives upon

hydrolysis coniferyl alcohol.

Hydrolysis
Lignin

coniferyl alcohol

Lignin is obtained in extremely large amounts as a by

product of timber industry.

Cardiac Glycosides
Steroidal in character with CPPP nucleus.
Powerful action on the cardiac muscle:

increase muscle contractility or tone of

cardiac muscle.
Steroid aglycones:
Cardenolides/ C23 steroid/ 5 member lactone
ring.
Bufadenolides/ C24 steroid/ 6 member lactone
ring.

Cardiac Glycosides
Identification Test:
Keller Killiani 2-deoxy sugar; reddish
brown color turn to blue purple
Liebermann Burchard steroid; blue green
to pink purple or violet;
Kedde test - lactone unsaturated; purple.

Digitalis or Foxgloves
Digitalis purpurea Linne.

FN: Scrophulariaceae
Most medically important

glycosides
Constituent/s:
Digitoxin

Gitoxin
Gitaloxin

Animal used in the assay:

guinea pig, frog, cats, pigeon.

Grecian Foxglove
Digitalis lanata Ehrhart

FN: Scophulariaceae
Source of digoxin
5 types of primary

glycosides:
lanatosides A to E
(diginalids)

Lily of the Valley

Convallaria majalis Linne

FN: Liliaceae
Dried rhizomes and roots:

Principal glycosides:
Convallatoxin
(strophanthidin and
rhamnose)
Minor glucosides:
Convallataxol and
Convalloside

Black Indian Hemp

aka Dog bane/ Canadian hemp

Apocynum cannabinum Linne

FN: Apoynaceae
Dried rhizomes and roots
Principal constituents: cymarin
Other constituents:

apocannosides and
cyanocannoside, adonotoxin, Kstrophanthin.

Adonis/ Pheasant Eye

Adonis aestivalis
FN: Ranunculaceae
Constituent/s:
Glycosides like:
Adonitoxin
Cymarin
K-stophantin

Black Hellerebore/
Christmas rose
Dried rhizosomes and

root of Helleborus
niger Linne
(Ranunculaceae).
Possesses cardiac

stimulant properties in
contrast to Green
Hellebore

Oleander (Adelfa)
Nerium oleander Linne
FN: Apocynaceae
Principal constituents:
Oleandrin
Used to treat cardiac

insufficiency.

Strophanthus
Dried, ripe seed of
Strophanthus kombe

Oliver
Strophantus hispidus
FN: Apocynaceae
Principal constituent:
K-strophanthoside
(stroposide)
Strophanthidin

Strophanthus
gratus
From seed of

Strophanthus gratus
Wall et Hook.
Baillon or from wood
of Acokanthera spp.
FN: Apocynaceae
Ouabain aka
G-strophanthin
extremely poisonous

Squill/ Squill bulb

Dried, fleshy, inner scales of the bulb of the

white variety of Urginea maritime Linne

Baker or Urginea indica Kunth (Liliaceae)
aka Mediterrian Squill respectively
Principal constituent:
scillaren A.

Minor constituent:
glucoscillaren A
proscillaridin A.
Uses:
expectorant, emetic, cardiotonic and diuretic.

Red squill
Bulb or bulb scales of

red variety of Urgenea

maritime linne Baker
(Liliaceae)
Use: rat poison

The CPPP Nucleus

Lactone ring
12
11
1
2

14
8

10
5

17

13

3
S ugar

CH3

OH
7

16
15

Cardiac Glycosides
The genins of all cardiac glycosides are

steroidal in nature, that act as cardiotonic

agents.
They are characterized by their highly specific
action cardiac muscle, increasing tone,
excitability and contractility of this muscle,
thus allowing the weakened heart to function
more efficiently.

Cardiac Glycosides
Cardiac glycosides that - unsaturated

5-membered lactose ring in position C17 are known as cardenolides.

Represented by the digitalis and
straphanthus group.

Cardiac Glycosides
Digitalis glycosides contain angular

methyl group at C-10,

Strophanthus glycoside are
characterized by presence of either an
aldehydic (CHO) or primary
alcoholic (C`H2OH) group at C-10.

Cardiac Glycosides O
OH 12
11
1
2
3

Sugar

Cardenolides
Digitalis glycosides
Strophanthus glycosides

14
8

10
5

17

13
9

CH3

OH

16
15

7
6

R=CH3
R=CHO OR CH2OH

Cardiac Glycosides
Cardiac agents that have

doubly unsaturated 6membered lactone ring in

position C-17 are referred
to as Bufadienolides.
This group includes the

squill glycosides and the

toad venom, Bufotoxin.

Cardiac Glycosides

OH 12
11
1
2

13
9

Bufadienolides
Squill glycosides
Bufotoxin

5
4

16

14

15

10
3

S ugar

17

R1
7

R1=OH, R2=H
R1 & R2 = ester group

R2

Cardiac Glycosides

Digitoxose

Cyamarose

Thevetose

Isolation difficulties
Major difficulty in the isolation of primary

glycosides from the crude drug...

Why?

The Cardenolides
Digitalis Group
D. purpurea, D. lanata, D. lutea and D. thapsi
O

R1
12

11
1
2

5
4

14
8

13
16

9
10

17

OH

R2

15

7
6

The structures of the common aglycones of the digitalis group

The Cardenolides
Digitalis Group
The primary glycosides Lanatoside A,

Lanatoside B, Lanatoside C are acted by

specific enzyme which split the terminal
glucose, give the secondary glycosides
acetyldigitoxin, acetylgitoxin and
acetyldigoxin respectively.
The deacetyl-lanatosides A, B and C can be
obtained by the alkaline hydrolysis of the
corresponding lanatosides.
Digitoxin, gitoxin and digoxin are obtained by
the action of alkali on their acetyl-derivatives.

The Cardenolides
Digitalis Group
Lanatoside A
purpurea gly. A
Specific
enzyme

Alkaline
hydrolysis

Specific
enzyme

Digitoxin

Acetyldigitoxin

Alkaline
hydrolysis

Acid hydrolysis
Digitoxigenin + 3 digitoxose

Strophanthus Group
Glycoside K-strophanthoside (a trioside),

K-strophanthin B (bioside) and cymarin (a

monoside) were isolated from different
strophanthus species.
The Primary glycoside K-strophanthoside

gives by hydrolysis one molecule of glucose

and the secondary glycoside Kstrophanthoside B or K- strophanthin B.

Strophanthus Group
The later gives by hydrolysis one molecule

of glucose and the tertiary glycoside

cymarin, which on turn hydrolyze into the
genin K-strophanthidin and the deoxysugar
cymarose.

Strophanthus Group
O

11
1
2
O

Cymarose
B-glucose
a-glucose

OH 6

17

K- strophanthidin

13
16

CHO 9
10
5

12

14
8

OH
7

15

Cymarin
K- strophanthin B
K- strophanthoside

Strophanthus Group
The seeds of Strophanthus gratus contains

another glycoside named Ouabain or (Gstrophanthin), which yield on hydrolysis

rhamnose and the aglycone ouabagenin.
Ouabagenin differs from K-strophanthidin

in having 2 additional (OH) groups at C-1

and C-11 and having a 1ry alcoholic group
at C-10 instead of the aldehydic group.

Strophanthus Group
O

OH
OH
OH
1

11
CH2 9
10

5
4

13
16
14

3
Rhamnose

12

17

OH
7

OH

Ouabain (G-strophanthin)

15

Bufadienolides
Group of cardioactive agents includes

the squill glycosides (the scillarins) and the

Toad poison (Bufotoxin).
Genins of squill glycosides differ from those
of the cardenolides in two important
aspects:
They have six membered doubly
unsaturated lactone ring in position C-17.
They have at least one double bond in the
steroid nucleus.

Bufadienolides

O
O

OH
Glucose-Glucose-Rhamnose

Scillaridin A
Proscillaridin A
Scillarin A
Glucoscillarin A

The ufadienolides of Squill

Name of glycosides
Structure
Glucoscillarin
Scillaridin A ---RHG---G
Scillarin A
Scillaridin A ---RHG
Proscillaridin A
Scillaridin A ---RHB

Physical and Chemical

Properties of Cardiac Glycosides
Solubility:
Different cardiac glycosides show different
solubilities in aqueous and organic solvents.
Usually soluble in water or aqueous alcohol and
insoluble in the fat solvents with exception of
chloroform and ethyl acetate.
The higher number of sugar units in the
molecule, the greater solubility in water
but lower soluble in chloroform.

Physical and Chemical

Properties of Cardiac Glycosides
Solvent extraction:
Alcohol is a good solvent for both the

glycosides and the aglycones. Solvent of

choice for the extraction of all CG from
drugs.
Petroleum ether and ether are used for
defatting process of drug, they do not
dissolve CG.

Physical and Chemical

Properties of Cardiac Glycosides
Stability:
Acid hydrolysis cleavage of the glycosides into
aglycones and sugar residues.
Specific enzyme usually coexist with cardiac
glycosides in plants, which may split the
primary glycosides into glycone with
less sugar units.
Cardiac glycosides deteriorate during
drying and storage unless special precautions
are taken.

Physical and Chemical

Properties of Cardiac Glycosides
Stability:
Protected against excessive

moisture

content and that these drugs should be stored in

sealed containers over dehydrating agents.
Heat stabilizes cardiac glycosides to destroy
the enzymes at higher temperatures. At higher
temperature, the tertiary OH group at C-14
may split off as water, leading to formation of an
inactive anhydro-form of cardiac
glycosides.

Physical and Chemical

Properties of Cardiac Glycosides

12
11
1 R
2

14
8

10
5

12

17
11

13

Sugar

CH3

OH

16

-H2O

15

Sugar

16

14
15

10
5

17

13

7
6

CH3

7
6

Physical and Chemical

Properties of Cardiac Glycosides
The gitoxin has in addition to tertiary OH at

C-14 another secondary OH at C-16.

Both OH groups split as water by the action
of H2SO4 with the formation of two
additional double bonds.
These with the double bond of the lactone
ring from a conjugated double bond system
that makes the compound fluorescent in UV
light.
(Refer to the previous slide )

Medicinal Importance
Cardiotonics, CHF, rheumatic heart

disease, atherosclerosis, HTN.

Diuretics (capillary of the kidneys are

dialated).

SAR of Cardiac
Glycosides
The glycone part displays a great

influence on the solubility and the rate of

absorption and distribution of the
glycosides to the site of action.
Small change in the molecules such as a
change of the location of the OH group,
modify the cardiac activity or even
eliminate it completely.

SAR of Cardiac
Glycosides
The saturation and/or cleavage of the

lactone ring, destroys the cardiac activity.

Therefore, the closely related CG, differ
greatly in the rate of absorption, duration of
action and their cumulative effect.

Cardiac drugs
Official in B.P. and USP
Digitalis leaf (digitalis tablets)
Digitoxin tablets 200g/tablet
Digoxin injection contain 0.0025% digoxin
Digoxin tablets contain 250g/tablet

Gitalin, lanatoside C, deslanoside,

strophanthus, strophanthin, ouabain and

squill.

Bitter Glycosides
Glycosides with bitter taste, also referred to

as bitter principle
Complex organic compounds containing
lactone ring, soluble in water and very
bitter in taste even in much diluted
solutions.
Increase the secretions of GIT by reflex
action and are used as stomachic, febrifuge
and bitter tonic.

Bitter Glycosides
Examples:
Gentiopicrin and amarogentin

from Gentian root and Chirata

Picroside and kutkoside from
Picrorrhiza,
Andrographolides from kalmegh
Quassin from Quassia wood
Cucurbitacins present in
Cucurbitaceae

Iridoid and secoiridoid

glycosides

Good source includes: Lamiaceae

(especially genera Phlomis, Stachys and
Eremostachys), Gentianaceae, Valerianaceae
and Oleaceae

Iridoid Glycosides
Devils claw
Harpagophytum procumbens
Family Name: Pedaliaceae
Constituent/s:
Harpagoside, Harpagide, Procumbine
(major)
Use/s:
Tx of osteoarthritis, rheumatoid arthritis,
indigestion and low back pain

Iridoid Glycosides
Picrorhiza
Picrorhiza kurroa
Family Name: Scrophulariaceae
Constituent/s:
Picrosides I-IV
Kutkoside
Use/s: Tx of indigestion, dyspepsia,

constipation, liver dysfunction,

bronchial problems and fever.

Secoiridoid Glycosides
Ash tree: Fraxinus excelsior
Olive tree: Olea europaea; Ligustrum

obtusifolium
Family Name: Oleaceae
Constituent:
Oleuropein
Use/s:
Hypotensive
Anti-oxidant
Anti-viral
Anti-microbial

Cysteine Derivatives
Occur as sulfoxides in the genus

Allium
Responsible for the lachrymatory factor of
onions and garlic.
S-(trans-propen-1-yl)-cysteine sulfoxide
present in onion
S-allyl derivative: present in garlic

Cysteine Derivatives
Garlic
SN: Allium sativum

FN: Liliaceae
Constituents:
Alliin
Alliin Allinase allicin
Diallydisulfide, diallyltrisulfide gives

the characteristic garlic odor

Miscellaneous Glycosides
STEROIDAL ALKALOIDAL

GLYCOSIDES: Solanaceae and

Liliaceae
With hemolytic property
- solanin: Present in potato (Solanum

tuberosum)
Soladulcin: Bitter-sweet (Solanum
dulcamara)
Tomatin: Tomato (Lycopersicon esculentum)
Rubijervin: Veratrum spp.

Miscellaneous Glycosides
GLYCOSIDAL RESINS
Convolvulaceae Family
Examples are: Jalap and Scammony
Upon hydrolysis will yield glucose,
rhamnose, fucose, fatty acids and hydroxyl
derivatives.

Miscellaneous Glycosides
BETALAINS give the bright color of
flowers and fruits of Family Cactaceae
Nitrogenous anthocyanins
Betacyanins: red violet
Betaxanthins: yellow
Betanin: upon hydrolysis will yield
betanidin (aglycone); indicaxanthin

Miscellaneous Glycosides
ANTIBIOTIC GLYCOSIDES

(Aminoglycosides)
Streptomycin
Streptidin (aglycone) a nitrogen containing

cyclohexane derivative
Streptobiosamine - glycone