Download Natural Products Chemistry

Anthraquinones
Professor Suleiman Olimat
Anthraquinone
Anthrone
O
Anthranol
O
1
8
OH
1
8
7
9
2 4H
7
9
2
6
10
3
6
10
3
5
5
4
H
O
H
4
H
O
2H
1
8
7
9
2
6
10
3
5
H
OH
Oxanthrone
4
Biosynthesis
Pharmacologial Characteristic of
Oxygenated Anthracene Cathartics
- The glycosides reach the colon via passage through the
intestinal tract and, to so me extent, via the circulation
after absorption in the small intestine.
- The glycosides are hydrolyzed in the lumen of the gut by
the bacterial enzymes. Of course the acidity of the
stomach also catalyzes the hydrolysis of some of the
glycosides.
- The cathartic effect is via a direct stimulation of the
colon.
- The action is observed in 6-8 hours after oral ingestion
and medication is usually conveniently taken prior to
retiring in the evening.
- These compounds and their metabolites may appear in
the breast milk during lactation and affect the infant.
Cont…
The metabolites may color the urine (red, orange,
pink, brown, black)
- Griping is the major adverse effect.
- Melanosis coli may develop in patients taking
these drugs over extended periods of time.
Melanosis coli is characterized by a melanotic
pigmentation of the colonic mucosa and is
confirmed via proctosigmoidoscopy.
- The pigmentation is benign and usually
reversible within 4-12 months after cessation of
therapy.
• 1- O-glycosides where the aglycone moiety is 1,8
dihydroxyanthraquinone derivatives, e.g.,
Gl O
8
O
OH
1
9
2
10
5
4
O
Aloe-emodin-8-glycoside
Gl O
O
8
9
OH
1
2
10
CH2OH
5
Gl O
O
8
9
O
Rhein-8-glycoside
2
10
COOH
4
OH
1
5
CH3
4
O
Chrysophanol-8-glycoside
Emodin-oxanthrone-9-glucoside
2- O-glycoside where the aglycone moiety partially
reduced 1,8 dihydroxy anthraquinone, e.g., Oxanthronetype.
Gl
OH
H
7
8
6
O
9
OH
1
3
10
5
4
O
2
Barbaloin
3- C-glycoside where the aglycone structure (anthrone
der.)
O
OH
7
8
6
5
H
OH
9
1
2
10
4
3
C6 H11 O5
CH2 OH
Sennoside A&B
4- O-glycosides where the aglycone moiety is di-anthrone
der. (i.e., dimmer) e.g., Sennosides where there is C-C
bridge between the anthranol units.
Gl
7
O
O
8
6
5
OH
9
1
2
10
4
3
H
COOH
H
COOH
Gl
O
O
OH
Senna Leaf
Consists of the dried leaflet of Alexandrian
or Khartoum senna, Cassia senna
(C.acutifolia), Tinnevelly senna
(C.angustifolia).
Chemistry
Dimeric anthracene glycosides derived from two
anthrones moieties which may be:
OH
8
O
OH
1
9
OH
2
10
5
4
Aloe-emodin anthrone
8
CH2 OH
O
OH
1
9
2
10
5
COOH
4
Rhein anthrone
Sennoside A&B
•
Similar anthrone moiety (Homo-dianthrones) i.e., 2- rhein
anthrone moieties condensate through two C-10 atomes. Thus it
can be exist in two optical forms, Sennoside A (L- form) &
Sennoside B (meso form).
Gl
7
O
O
8
6
5
OH
9
1
2
10
4
3
H
COOH
H
COOH
Gl
O
O
OH
Sennoside C&D
•
Or different (Hetero-dianthrones) i.e., one rheinanthrone & one emodin anthrone, Sennoside C (Lform) and Sennoside D (meso form).
Gl
7
O
O
8
6
5
OH
9
1
2
10
4
3
H
CH2 OH
H
COOH
Gl
O
O
OH
Cascara
The dried bark of Rhamnus purshiana
Family Rhamnaceae. B. P. specified that
the collection must be made
at least one year before the bark is used
(fresh bark contains an emetic principle).
Csacara
Chemistry
1- cascarosides A&B (glycosides of
barbaloin)
2- cascarosides C&D (glycosides of
chrysaloin)
Frangula Bark
The bark of Frangula purshiana
Frangulin (frangula emodin rhamnoside).
Glucofrangulin (frangula emodin glucorhamnoside).
OH O
OH
RO
CH3
O
Frangulin
R= Rhamnose
Glucofrangulin R= Rhamnose-glucose
Frangula
Rhubarb
The rhizomes of Rhubarb (Rheum spp.) family
Polygonaceae.
Consist of glycoside of rhein, rhein anthrone,
chrysophanol and aloe emodin.
The presence of tannins in rhubarb makes the
drug constipating. So in small doses, rhubarb
exerts no purgative action but acts only as
intestinal astringent, but large doses cause
purgation.
Chemistry
O
OH
H
OH
Gl
O
O
CH2 OH
Gl
CH2 OH
H
Gl
Cascaroside A& B
Barbaloin
O
OH
H
OH
OH
Gl
CH3
Gl
Chrysaloin
O
O
H
OH
CH3
Gl
Cascaroside C & D
Aloes
• Aloe is the dried latex of the leaves of a number of
species of the genus Aloe (Liliaceae).
• The major glycoside being the C-glycoside barbaloin.
Note
The 1ry glycosides are more active than the
aloins while the free anthraquinon have
little purgative activity.
Uses
• The laxative action of the crude drugs is always
higher than from their content of anthracene der. The
different anthracene der. contained by the crude
drug are said to exert a synergistic action.
• Thus, the naturally occurring anthracene glycosides
were found superior to the synthesis of numerous
hydroxyl anthracene der.
• Some of these synthetic compounds act too
drastically and also caused kidney damage.
• The only compound which is used to some extent in
current medicine is danthrone. It is also used as a
standared in colorimetric assays of anthraquinone
glycosides.
. •
Danthrone
OH
O
O
OH
Effect of storage on the active of
anthracene glycosides
Prolonged storage of anthracene bearing drugs may
bring oxidation of anthranols and anthrones to
give the less active anthraquinones. Thus, the
activity of drugs decreases by time. However,
anthraquinone glycosides do not cause any
griping action (like anthranol and anthone), thus
no antispasmodic such as belladonna is
prescribed with them.
Drugs as senna, Aloe and cascara preparations retain
their activity for a long time.
Cascara and frangula must be aged for one year before
it is used for medicinal preparation.
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
Asphodelus spp.
• Asphodelus aestivus Brot. (Syn.
Asphodelus microcarpus Salzm),
Family Liliaceae, is a perennial herb
with short vertical rhizome is widely
distributed throughout Jordan.
Flowering period is January-April.
Ramosin
• Ramosin is the major one and the extract
of the plant is standardized according to
the percentage of Ramosin is a reference
standard.
•
OH
O
OH
OH
OH
HO
O
O
HO
OH HO
OH
OH
Expected uses
– Due to the presence of anthraquinone
glycosides.
• To treat sore gums and mouth ulcers.
• To treat oral infectious diseases like dental
caries and periodontitis.
• To treat oral aphthous.