Glycosides Classification

Classification
• On the basis of aglycone structure
• [2] Cardiac glycosides (poisons)
• from squill, digitalis, lily of the valley
• used as crow poisons through history
• aglycone = steroid
 History
• Herbal arrow poisons as hunting weapons
• Toxicity. From ancient times, humans have
used cardiac-glycoside-containing plants and
their crude extracts as arrow coatings,
homicidal or suicidal aids, rat poisons, heart
tonics, diuretics and emetics, primarily due to
the toxic nature of these compounds
 Cardiac glycosides
• Plant glycosides with specific action on heart
• Historical use:
– arrow poisons
• Historical sources:
– South American toad skins, African plant extracts

• Modern use:
– to treat congestive heart failure
– aglycone structure important for activity
Sources
• Scrophulariaceae
• Digitalis purpurea leaves (foxglove)
• Digitalis lanata leaves – white flowers

• Apocyanaceae
• Strophanthus vine seeds – Africa

• Liliceae
• ‫بصيل‬Urginea bulbs (squill) –M.E.
Europe, India, Asia
• Convallaria leaves (lily of the valley)
– also produces a volatile oil perfume
 Scrophulariaceae
• Is foxglove poisonous to humans?
• Foxglove (Digitalis purpurea L.) leaves are frequently
confused with borage (‫حمحم‬Borago officinalis L.), which is
traditionally used as a food ingredient.
• Due to the presence of the cardiac glycosides, mostly
digitoxin, foxglove leaves are poisonous to human and may
be fatal if ingested
what is Digitalis lanata used for?
• Chemicals taken from foxglove are used to
make a prescription drug called digoxin.
Digitalis lanata is the major source of
digoxin in the US.
• Most commonly used for heart failure and
fluid build up in the body (congestive heart
failure ) and irregular heartbeat.
 What is difference between
digoxin and digitoxin?

digoxin C41H64O14
digitoxin
C41H64O13
 Active compounds
• steroid nucleus
• C14 = OH
• C3 = OH
– sugars attached
• C17 = lactone ring
– classified into 2 groups

Cardenolides Bufadienolides
more common
opens in alkali
 StrophanidiolStrophanthus Scillarenin (squill)

• sugars:
– 1-4 β-linked at C3 in various combinations
– glucose, rhamnose, deoxy-sugars
• eg digitoxose, digitalose
digitoxose, digitalose

A deoxy-sugars C6H12O4 2,6-Dideoxy-D-ribo-hexopyranose

glucose C6H12O6
 digitoxose, digitalose
Digitalose is a deoxy sugar that is a component of various cardiac
glycosides Chemically, it is a methyl ether of D-fucose.

6-Deoxy-3-O-methyl-D-galactose D-galactose
Digitalis
• Scrophulariaceae family
– biennial flowering plants
• Poisoning
• natural emetic if eaten
– Digitalis purpurea leaf – purple, British
• -> Digitalis Tablets B.P.
• -> Tincture of Digitalis B.P.
• commercially grown Holland, E. Europe
• no extraction for these products
– Digitalis lanata leaf – white,
Mediterranean
• used for manufacture of pure glycosides
• i.e. digoxin, lanatoside C
• commercially produced Holland, Equador,
USA
 Chemistry
of D.lanata
• compounds belong to
cardenolide series
– 5 membered lactone ring
– approx 96 compounds

* Acetyl group confers

crystalline properties -
makes compounds more
easily isolated
Gitaloxin is a cardenolide glycoside that is gitoxin in which the 16beta-
hydroxy group has been formylated. It has a role as a metabolite. It is
functionally related to a gitoxin.

formylester

3 Digitoxose

gitaloxigenin
gitaloxin
 Digitoxose
• sugar found on primary glycosides of D.lanata
• glucose on the end of a chain of O-linked digitoxose
sugars at C3
• during harvesting and drying enzymes can remove
acetyl groups and the end glucose
– after collection dried as rapidly as possible at 60oC,
stored in airtight containers protected from light
(contain no more than 6% moisture)
 Important ones:
– Digoxin “Lanoxin” – 0.25 μg white tablet
• Digitoxin “Digitalin” 0.25 μg small pink
tablet
• Lanatoside “Cedilanid” 0.10 μg
Some cardioactive glycosides from D.lanata:

Ref: Trease & Evans

Lanatoside A B C and D
 digitoxigenin gitoxigenin

digoxigenin diginatigenin
Gitaxogelinin:
 Digitalinum Verum
• Gitoxigenin 3-O-[β-D-glucopyranosyl-(1→4)-β-D-
digitalopyranoside]
 ‫االسم لالطالع‬Glucoverodoxin

(3beta,5beta,16beta)-3-((6-Deoxy-4-O-beta-D-glucopyranosyl-3-O-methyl-
beta-D-galactopyranosyl)oxy)-14,16-dihydroxycard-20(22)-enolide 16-
formate