1. Flavonoids
Ph.D.Ahmed Metwaly
Email: ametwaly@azhar.edu.eg
• Associate Professor of Pharmacognosy , Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt
• Associate Professor, Biopharmaceutical Products Research Department, Genetic Engineering and Biotechnology
Research Institute, City of Scientific Research and Technological Applications (SRTA-City), Alexandria, Egypt
• Senior research fellow, Liaoning University of Traditional Chinese Medicine, China (20118-2019)
• Visiting scholar, School of Pharmacy, University of Mississippi, USA (2012-2014)
2.
3. FLAVONOID GLYCOSIDES
• Flavonoids one of the largest group of naturally occurring metabolites.
• They occur in the plant in both free and as glycosides.
• This group is regarded as C6-C3-C6 compounds (15 carbons) in which each C6
moiety is a benzene ring.
(Latin, flavus, yellow).
Function in plants:
1-As flower pigments where they attract pollinating birds and insects.
2-A control of plant growth by inhibiting and activating enzymes.
3-Some have fungicidal properties.
Flavonoid
Skeleton
4. • The different classes within this group are distinguished by additional oxygen
heterocyclic Rings and by OH groups distributed in different patterns
• Flavan itself is colorless, but many of its hydroxylated derivatives are colored.
• The intensity of the yellow color increases with the number of OR groups and
with increase of pH.
• The largest group of flavonoids is characterized by the presence of a pyran
ring that links the 3 carbon chain with one of the benzene rings.
5.
6. Increasing the number of phenolic hydroxyls results in:-
++ Hydrophilic characters
++ Acidic nature.
++ UV & light absorption.
++ Chemical reactivity.
-Glycosides are generally soluble in H2O and ethanol; insoluble in organic
solvents.
-The genins (aglycon) are only sparingly soluble in H2O but are soluble in ether.
-They dissolve in alkali yellow solutions which on addition of acids become
colorless or less yellow.
Solubility:
7. Action and therapeutic uses
1- Cardiotonic (e.g. procyanidins in Crateagus spp).
2 -Antioxidant (e.g. Catechins in green tea leaves).
3 -Antiviral (e.g. flavonoids in liquorice).
4 -Anticancer (e.g. isoflavonoids in soya bean).
5- Reduction of capillary fragility (e.g. Rutin in Ruta spp and Diosmin in buchu leaves).
6- Diuretic (e.g. flavonoids in buchu leaves).
7- Antihepatotoxic (e.g. flavolignans in Silybium marianum).
8-The isoflavone derivatives have a distinct estrogenic effect due to the stilbin structure
That results from ring opening
8. The different types of flavonoids can be characterized by:
Their colored response to different tests (visible light)
Colored fluorescence in UV light.
1- Reaction with aluminum chloride: The different classes of flavonoids give a
yellow color with AlCl3 but fluoresce differently in UV as shown in the following table:
Color tests for identification
Light Flavones Flavonols Flavanones Chalcones
Visible yellow yellow yellow yellow
UV Green Yellowish to
Yellowish-green
Pale- brownish Brownish pink
9. 2- Lead subacetate test: All flavonoids give a yellowish precipitate.
3- Shinoda's test for flavanones and flavonols: Alcoholic solution + Mg metal
/ HCl, an orange, red or violet color is produced.
4- Antimony pentachloride test for chalcones: Alcoholic solution + SbCl5/CCl4, a
red or violet color is produced.
10. Isolation
Flavonoids and their glycosides are extracted from the plant material as follows:
1- Extraction
⮚Glycosides are polar (due to the sugar moiety and highly hydroxylated) and
extractable with alcohol, water and hydroalcoholic solution.
⮚Aglycones are extracted with less polar solvents e.g. ether, chloroform and ethyl
acetate
2- Purification
by one of the following methods:
⮚Shaking with Na2CO3 or NaHCO3 (in case of compounds containing strong acidic OH
groups at C-7 and or C-4').
⮚Precipitation with Pb acetate.
⮚Chromatographic techniques e.g. PC,TLC or CC.
11. UV spectra are useful for:-
⮚ Determination of the basic structure
⮚ Estimation of the number and position of OH groups.
⮚ Diagnostic reagents which may cause shifts in the Position of
the maximum wavelength are used.
⮚ The spectra are recorded in methanol in the absence and
/or presence of different shift reagents i.e. NaOMe, AlCl3,
AlCl3/HCl, NaOAc and NaOAc/H3BO3.
Band I
Band II
12. − AlCl3 solution forms a complex with orthohydroxyl groups in
ring A or B (which is unstable on addition of HCl), and thus
results in a hypsochromic shift in Band I relative to the AlCl3
spectrum
13. I. FLAVONE GLYCOSIDES:
l- Apiin (5, 7, 4'- trihydroxy flavone-7-g1ucoapioside)
⮚Occurance: It is present in leaves and seeds of parsley (Petroselinum sativum )
⮚Chemical tests
• Apiin + FeCl3 → reddish brown color.
•It gives a yellow color with alkali and yellow precipitate with lead acetate.
⮚Uses: Anti- bacterial, anti-fungal, anti-oxidant and anti- inflammatory effects
14.
15. 2- DIOSMIN = BAROSMIN (5, 7, 3'-TRIHYDROXY-4'-METHOXY FLAVONE-7-
GLUCORHAMNOSIDE)
Hydrolysis:
Acid hydrolysis→
rhamnose + glucose + diosmetin
Occurrence:
It occurs in Buchu leaves, Conium and Dahlia.
Uses:
It reduces capillary fragility, therefore used as
prophylactic and in treatment of varicose veins
and in acute hemorrhoids.
17. II- FLAVONOL GLYCOSIDES:
1- Rutin (5, 7, 3', 4'-Tetrahydroxy flavonol-3-
glucorhamnoside)
Hydrolysis:
Rutin, on reflux with 1N H2SO4,
yields quercetin + glucose + rhamnose.
Chemical tests
Rutin + FeCl3 → green color.
Rutin + PbAc → yellow precipitate.
Uses
Rutin reduces capillary fragility, permeability and
bleeding.
18.
19. ACYLATED FLAVONOL GLYCOSIDES
Occurance: Gingko biloba
⮚The main active constituents of G. biloba leaves are acylated flavonol glycosides of
kaempferol, quercetin, and isorhamnetin.
Uses: Cerebrovascular insufficiency and poor arterial circulation.
20. III-FLAVANONE
GLYCOSIDES:
Flavanone Flavone
have a reactive C=O, they react with
hydroxylamine to form oximes
-ve
with strong alkali: benzaldehyde +
acetic acid + phenol
with strong alkali give: cinnamic
acid + phenol
21.
22. 1-HESPERIDIN (HESPERITIN-7-RUTINOSDE):
▪ It occurs in the peel of unripe Citrus fruits,
e.g. 5-14% in that of bitter orange and gradually
disappears on ripening.
⮚ Effect of acid Hesperidin is hydrolysed to
hesperitin + rhamnose + glucose.
⮚ Effect of alkali, it is converted to hesperidin
chalcone.
23. Chemical tests
▪Hesperidin + FeCl3 solution → wine-red color.
▪Alc. solution of hesperidin + Mg metal + conc. HCl → Violet color.
Uses
Hesperidin is necessary for the absorption of vitamin C.
▪It reduces capillary fragility and is used for correction of capillary permeability in
cerebrovascular or cardiovascular diseases and hypertension.
24. 2- Liquiritin (liquiritigenin-4`-glucoside)
▪ Isolated from Liquorice roots, were found clinically effective in gastric
and duodenal ulcers, as well as, anti-inflammatory.
▪ They are the main constituents of DGL (Liquorice extract almost free
from Glycyrrhizin, the triterpenoid saponin of Liquorice).
25. IV- FLAVANONOL GLYCOSIDES
Action and Uses
They are antioxidants, hepatoprotectives, and prevent
cataract formation in diabetic patients.
* Occurance: in the roots of Smilax glabra,
and Astilbe spp.
26. V-ISOFLAVONOID GLYCOSIDES:
Daidzin and Genistin
(Soya bean)
Pharmacological action and uses
✔Treatment of osteoporosis.
✔Dietary phytoestrogens.
✔Cancer-protective compounds as
Preventing breast and prostate cancer.
27. VI. ANTHOCYANIDINS AND THEIR GLYCOSIDES:
- Their glycosides are known as anthocyanins.
- These names are derived from the greek antho (flower) and kyanos
(blue).
- They occur in the dissolved state in the cell sap of the flowers, fruits
and other organs.
⮚ The color of these compounds is pH dependent. For example, the blue
color of cornflower is due to the alkaline pH of its cell sap and the red
color of roses is due to acidic pH of its cell sap, in both cases, the
color is due to the same anthocyanin, cyanidin 3, 5-diglucoside.
28. Flavan-3-ols
General characters
▪These compounds do not possess a keto group at C-4.
▪The most commonly occurring natural products in this class are catechin, epicatechin and
the proanthocyanidins (the most common class of polyflavanoids, which are polymers
consisting of catechin or epicatechin units).
29. Catechin and epicatichen
Occurrence
⮚They occur in green tea, fresh leaves of Camelia sinensis
(epigallocatechin and its gallate derivative),
⮚ in rhubarb tannins (epicatechin, its gallate, and its polymers),
⮚ in hawthorn (Crataegus sp.)
⮚ in black tea (theaflavins).
30. Pharmacological action and uses
▪They are used as Fat burner, antioxidants (against lipid peroxidation),
anticancer, antiviral and antibacterial.
▪(-)-Epicatechin and its 3-O-gallate derivative contribute mainly to the
antiuremic action of aqueous extract of rhubarb, which is effective in renal
failure.
31.
32. FLAVONOID CONTAINING COMPOUNDS
Silymarin (Milk thistle)
a mixture of various flavanonol and flavanol derivatives
present only in the fruits of Silybum marianum.
The principal components of silymarin are: silybin,
silychristin and silydianin
Silibin A and silibin B structures
33. Uses
It acts as hepatoprotective and as a prophylactic in treatment of:
▪Liver damage caused by metabolic toxins.
▪Liver dysfunction after hepatitis.
▪Chronic degenerative liver conditions, e.g. liver cirrhosis and fatty liver.
▪The oxeran ring is responsible for the antihepatotoxic effect of silybin,
and opening of this ring results in loss of activity
