FLAVONOIDS

FLAVONOIDS
•The flavonoids are polyphenolic compounds possessing 15
carbon atoms; two benzene rings joined by a linear three
carbon chain having the carbon skeleton C6 - C3 - C6 and
they are the plant pigments and they are having polar
nature and is solouble in methanol and water.
•Flavonoids constitute one of the most characteristic classes
of compounds in higher plants. Many flavonoids are easily
recognised as flower pigments in most angiosperm families
(flowering plants).

• However, their occurence is not restricted to flowers but
include all parts of the plant.
• They are secondary metabolite and effective in CNS
disorders.

Flavonoids
Act like antioxidants. How effective they are depends on
their molecular structural characteristics
Some flavonoids in hops and beer have been found to
have better antioxidant effects than tea or red wine; most
flavonoids are found in fruits, vegetables, teas, and other
drinks.
Flavonoids have been known to have antiviral, anti-
allergic, antiplatelet, anti-inflammatory, antitumor and
antioxidant activities

Flavonoids
 Polyphenolic
compounds with 15 C
atoms, 2 benzene rings
on linear 3 C chain
Over 4,000
flavonoids
Easily recognized as
flower pigments in most
angiosperm plants but
are not always flower
pigments
 In plants they repair
damage and shield from
environmental toxins
The Most Important Classes of Flavonoids and their Biological
Significance
Class
number of known
members
biological significance
(so far as known)
anthocyanin(s) 250 red and blue pigments
Chalcones 60 yellow pigments
Aurones 20 yellow pigments
Flavones 350
cream-coloured
pigments of flowers
Flavonols 350
feeding repellents (?)
in leaves
Dihydrochalcons 10 some taste bitter
Proanthocyanidins 50 astringent substances
Catechins 40
some have properties
like those of tannins
Isoflavonoids 15
oestrogen effect, toxic
for fungi

TESTS FOR FLAVONOIDS
🞭 The extracts were dissolved in ethanol, filtered and
subjected to following tests.
🞭 Shinoda test: The dried extracts were dissolved in 95%
ethanol (5ml) and few drops of concentrated
hydrochloric acid (HCL) were added. Then the
magnesium turnings were put into the solution and
observed for appearance of pink color.
🞭 Lead acetate solution test: To small quantity of above
residue, lead acetate solution was added and observed for
appearance of formation of yellow colored precipitates.

CORE STRUCTURES AND
NOMENCLATURE
• The nomenclature of flavonoids
proper is straight-forward with the
aromatic ring A condensed to the
heterocyclic ring C and the
aromatic ring B most often
attached at the C2 position. The
various substituents are listed first
for the A and C ring and - as
primed numbers - for the B ring
(note that the numbering for the
aromatic rings of the open-chained
precursor chalcones is reversed).
• (Harborne JB, ed. (1988) The Flavonoids.
Advances in Research. Chapman & Hall.)
O O
OH
OH
O O
O O
OH
O
OH
+
O
Flavanone
O
Dihydroflavonol Flavan-3-ol
Flavone Flavon-3-ol Anthocyanidin
OH
O
Chalcone
A
B
O
O
Isoflavone
O
Neoflavone
A
B
O
C
Flavonoids Society For Free Radical Biology and Medicine W
. B

FLAVONOIDS & THEIR EXAMPLES
🞭 Flavone:-
🞭 Flavonol:-
Luteolin, Apigenin, Tangeritin
Quercetin, Kaempferol, Myricetin,
Fisetin, Isorhamnetin,
Pachypodol, Rhamnazin
🞭 Flavanone:- Hesperetin, Naringenin,
Eriodictyol, Homoeriodictyol
🞭 Flavanonol- Taxifolin, Dihydrokaempferol

FLAVONES
🞭 These are yellow pigments which occur in plant
kingdom either in the free state or as glycosides
associated with tannins.These are also known as
anthoxanthins.
🞭 Chemically they are hydroxylated derivative of
flavone(2-phenyl-4-chromone) which are partially
alkylated.
🞭 In most of the flavones, positions 5 and 7 are
hydroxylated and also one or more positions 3,4,5 are
also hydroxylated.Further positions 3’and 5’are often
methylated whereas positions 5,7 and 4’ are usually
unmethylated.

🞭 When a flavone is hydrolysed with mineral acid, it yields
an aglycon and one or more molecules of sugars. The
sugars are generally glucose, rhamnose etc. Flavones may
exist as C-glycosyl derivatives as well as O-glycosides, eg:
vitexin and isovitexin
G
HO O
OH
G
HO O
OH
OH O
OH O
O
O
C h r o m o n e F l a v o n e
1
O
2
3
4
O
5
6
7
8
1'
2'
3'
4'
5'
6'

PROPERTIES OF FLAVONES
🞭 Most flavones are yellow solids
🞭 Most flavones are soluble in water, ethanol and dilute
acids and alkalis.
🞭 Flavones are precipitated by lead salt.
🞭 With ferric chloride, flavones give either a dull green or
a red brown colour.

OH
O
+
Cl
-
O
Cl
-
+
H
+
O
+
O OH}Cl-
Different structures of oxonium salts of flavones.
Flavones exhibit two absorption bands: Band I 330-350 nm and Band II,250-270
In acidic medium, flavones are usually more highly
coloured than the bases from which they are derived. In
acidic medium flavones form oxonium salts which impart
this colour. However these oxonium salts are very
unstable in presence of water. The flavones differ in this
respect from the anthocyanidins which give strong
oxonium salts and are found as such in plants.

Diluted with water,acidified with HCl and boiled for some ho
Exctracted with alcohol &
carried out fractional crystallis
Digestion with boiling water
Water extract
diluted and treated with lead acetate
Filteration
Precipitate of
tannins
Flavonoids in
supernatant liquid
Ground plant material
Acetate free flavonoids
Precipitate of sugar
free flavonoids

SEPARATION & PURIFICATION OF
FLAVONES
PAPER CHROMATOGRAPHY
🞭 Convenient means of separating and purifying
flavones on milligram scale
Dried plant material is extracted with either 70 % or 80 % methanol.
The aqueous extract is then concentrated to a small volume in
vacuo and refiltered if necessary.
An aliquot of this concentrate should be applied on Whatman No. 3
filter paper.

Separation of the flavones present in concentrate is generally
carried out in the solvent mixture BAW(n-butanol-acetic acid-
water),4:1:5
Individual bands are eluted and concentrated .
Further fractioned in water, 5 % acetic acid.
Purified in n-butanol-ethanol-water(4:1:2.2)

GENERAL METHODS FOR THE ELUCIDATION OF
STRUCTURE OF FLAVONOLS
🞭 Flavonol shows characteristic bands at 350-390 nm and 150-270 nm in
ultraviolet spectrum.
🞭 The molecular formula of flavonol has been found to be C15H10O3
🞭 It can be acetylated to give an ester shows the presence of a hydroxyl
group.
🞭 C15H9O2(OH)+ CH3COCl
C15H9O2(OCOCH3)+HCl
🞭 When methylated followed by fusion with KOH, flavonol yields phenol
and benzoic acid. Both these products do not possess methoxyl group.
This shows that the methoxy group must be present at C3 which must
have been lost in KOH fusion.
C 1 5 H 1 0 O 3
M e t h y l a t i o n
a n d f u s i o n w i t h K O H
O H
+
C O O H
f l a v o n o l p h e n o l b e n z o i c a c i d

🞭 When flavanol is boiled with an ethanolic solution of
potassium hydroxide, it yields a mixture of o-
hydroxybenzoylmethanol and benzoic acid. The formation of
these products reveals that flavonol contains a hydroxy group
at C3. Hence flavanol must be 3-hydroxyflavone(3-hydroxy-
2-phenyl-ϒ-chromone)
🞭 On the basis of the above structure of flavanol,the foregoing
reactions can be explained as follows:
O
C 6 H 6
O H
O
Fl a va n o l

O
O
C6H6
OH
Flavanol
+ CH3COCl
O
O
C H
6 6
+ HCl
OCOCH 3
Acetyl derivative of flavonol
O
O
C6H6
OH
methylation
(CH3)2SO4/NaOH
O
O
C6H6
OCH 3
KOH
Fusion
HOOC
+
OH
Phenol Benzoic acid
O
O
C6H6
OH
KOH
Boiling
OH
O
OH
C6H5
OH
OH
O
COC 6H5
OH
OH
+ C6H5COOH
COCH 2OH
o-hydroxybenzoyl methanol Benzoic acid
a)
b)
c)

Synthesis
The above structure of flavanol has been confirmed by its
various syntheses
a)Robinson’s synthesis.
In this synthesis ω-methoxy-2-hydroxyacetophenone is
condensed with benzoic anhydride in the presence of its
potassium salt
OH
COCH 2OMe
+ (C6H5CO)2O
O
OMe
C6H5
O
HI
O C6H5
OH
O
Flavanol

QUERCETIN

USES
🞭 Preliminary research
🞭 Antiviral
🞭 Hyperoside (which is the 3-O-galactoside of quercetin) is
a strong inhibitor of HBsAg and HBeAg secretion
🞭 Quercitrin and myricetin 3-O-beta-D-galactopyranoside
inhibit HIV-1 reverse transcriptase, all with IC50 values
of 60 μM.
🞭 Quercetin can also inhibit reverse transcriptase, part of
the replication process of retroviruses. The therapeutic
relevance of this inhibition has not been established.

🞭 Asthma
🞭 Quercetin is an effective bronchodilator and helps reduce the
release of histamine and other allergic or inflammatory chemicals
in the body.
🞭 Quercetin has demonstrated significant anti-inflammatory activity
because of direct inhibition of several initial processes of
inflammation.
🞭 Eczema
🞭 Serum IgE levels are highly elevated in eczema patients, and
virtually all eczema patients are positive for allergy testing.
Excessive histamine release can be minimized by the use of
antioxidants. Quercetin has been shown to be effective in reducing
IgE levels in rodent models.

🞭 Inflammation
🞭 Several laboratory studies show quercetin may have anti-
inflammatory properties, and it is being investigated for a wide
range of potential health benefits.
🞭 Quercetin has been reported to be of use in alleviating symptoms of
pollinosis. An enzymatically modified derivative was found to
alleviate ocular but not nasal symptoms of pollinosis.
🞭 Studies done in test tubes have shown quercetin may prevent
immune cells from releasing histamines which might influence
symptoms of allergies.
🞭 A study with rats showed that quercetin effectively reduced
immediate-release niacin (vitamin B3) flush, in part by means of
reducing prostaglandin D2 production. A pilot clinical study of four
humans gave preliminary data supporting this.
🞭 Quercetin may have properties of a calcineurin inhibitor, similar to
cyclosporinAand tacrolimus, according to one laboratory study.

🞭 Fibromyalgia
🞭 Quercetin may be effective in the treatment of fibromyalgia because
of its potential anti-inflammatory or mast cell inhibitory properties
shown in laboratory studies
🞭 Cancer
🞭 Laboratory studies have investigated Quercetin's potential for use in
anti-cancer applications. The American Cancer Society says quercetin
has been promoted as being effective against a wide variety of
diseases, including cancer.

🞭 Metabolic syndrome
🞭 Quercetin has been shown to increase energy expenditure in rats, but only
for short periods (fewer than 8 weeks). Effects of quercetin on exercise
tolerance in mice have been associated with increased mitochondrial
biogenesis.In mice, an oral quercetin dose of 12.5 to 25 mg/kg increased
gene expression of mitochondrial biomarkers and improved exercise
endurance.
🞭 It has also been claimed that quercetin reduces blood pressure in
hypertensive and obese subjects in whom LDL cholesterol levels were also
reduced.
🞭 In vitro studies showed quercetin and resveratrol combined inhibited
production of fat cells and vascular smooth muscle cell proliferation.
🞭 Supplements of quercetin with vitamin C and niacin does not cause any
significant difference in body mass or composition and has no significant
effect on inflammatory markers, diagnostic blood chemistries, blood pressure,
and blood lipid profiles.

🞭 Monoamine-oxidase inhibitor
🞭 Possibly an active component of heather (Calluna vulgaris), quercetin
was suspected from a bioassay test on crude extracts to selectively
inhibit monoamine oxidase, possibly indicating pharmacological
properties.
🞭 Prostatitis
🞭 Quercetin has been found to provides significant symptomatic
improvement in most men with chronic prostatitis, a condition also
known as male chronic pelvic pain syndrome.

REFERENCES
🞭 1)Organic chemistry of natural products; vol 1 ;
O.P. Agarwal ; pg no :350-406
🞭 2)Organic chemistry of natural products ; vol 2;
Gurdeep. R. Chatwal ; pg no : 2.1 – 2.40
🞭 3)Organic chemistry ; vol 2 ; stereochemistry &
chemistry of natural products ; I. L .Finar ;
5th edition ; pg no : 425