FLAVONOIDS General characteristic 1

Plan

1. The general characteristic

of flavonoids

2. Physical and chemical

properties of flavonoids

3. Qualitative and

quantitative determination

of flavonoids

Flavonoids are the largest group of naturally occurring

phenols and occur in the plant both in the free state and

as glycosides.

They may be described as a series of C6-C3-C6

compounds.

Classification

The largest group of flavonoids is characterized by the

presence of a pyran ring linking the three carbon chain

with one of the benzene rings.

The numbering system for these flavonoid derivatives is as

follows:

AB

6' 5'

4'

3'2'

1'

8

7

6

5 4

3

21

CB

A

O

3

Flavonoids are distinguished by the

place of B-ring location :

O

AB

C

Isoflavonoids

6' 5'

4'

3'2'

1'

8

7

6

5 4

3

21

CB

A

O

True flavonoids

O

A

B

C

Neoflavonoids

4

True flavonoids are classified according to the

oxidation level of the propane moiety of the

molecule.

O

OH

O

OH

OH

O

OH

+

O

O

O

O

OH

O

O

OH

O

O

OH

O

O

O

CH

Catechins Leucoanthocyanidins

Anthocyanidins

Flavanones Flavanonoles

Flavones Flavonoles Aurones

Chalcones

5

ISOFLAVONOIDS

6

O O

O

O

OH

OH

O

O

O

O O

7

10

9

8

O11

3

2

1

4O5

O

A B

C D

6a

11a 12

O7

O5

68

9

10

11

1

2

3

4

A

BCD

6a

12a

O

O

A B

C D

6a

11a

Simple isoflavonoids

Isoflavan Isoflavanone Isoflavanol

Isochalcone Isoflavone 3-arylcoumarin

Condensed isoflavonoids

Coumestane Rotenoid Pterocarpane

THE MOST WIDE-SPREAD COMPOUNDS

Flavonoles

Apigenin

OOH

OH

OOH

OOH

OH

OH

OOH

Luteolin

OOH

OH

O CH3

OOH

Diosmetin

Kaempferol

OOH

OH

OH

O

OH

OOH

OH

OH

OH

O

OH

Quercetin

OOH

OH

OH

OH

O

OH

OH

Myricetin

Isorhamnetin

OOH

OH

O CH3

OH

O

OH

Flavones

O

OH

OH

OH

O

OH

CH3O

Rhamnetin

7

Flavonoid glycosides Rutin, Hyperoside, Quercetrin

Flavonoids are widely distributed in nature either

in a free state or linked to sugars, which are more

common in higher plants and in young tissues,

where they occur in the cell sap.

Flavonoids are of abundant in the Polygonaceae,

Rutaceae, Fabaceae, Rosaceae.

O

OOH

OH

OH

OH

O-Gala

O

OOH

OH

O-Rha

OH

OH

8

Rutin Hyperoside Quercetrin

O

OOH

OH

OH

Glu

Vitexin

BIOSYNTHESIS:

Flavonoids are products from a cinnamoyl-CoA

(C6C3, precursor from the shikimate pathway)

starter unit, with chain extension using three

molecules of malonyl-CoA.

Flavonoids are therefore of mixed biosynthesis,

consisting of units derived from both shikimate

and acetate pathways.

9

10

The triketide starter unit undergoes cyclization

by the enzyme chalcone synthase to generate the

chalcone group of flavonoids. Cyclization can

then occur to give a pyranone ring containing

flavanone nucleus, which can either have the

C2-C3 bond oxidized (unsaturated) to give the

flavones or be hydroxylated at position C3 of the

pyranone ring to give the flavanonol group of

flavonoids. The flavanonols may then be further

oxidized to yield the anthocyanins, which

contribute to the brilliant blues of flowers and

the dark colour of red wine.

11

FUNCTIONS IN PLANTS

Control of the plant growth;

Inhibiting and activating the enzymes;

Having a role in the biochemistry of

reproduction;

Fungicidal properties;

Protect the plant from parasites’ attack;

12

These compounds have high ecological

importance in nature as colour attractants to

insects and birds as an aid to plant pollination.

The flavonoids contribute to many other colors

found in nature, particularly the yellow and

orange of petals; even the colourless flavonoids

absorb light in the UV spectrum (due to their

extensive chromophores) and are visible to

many insects. [A chromophore is the part (or moiety) of

a molecule responsible for its color].

13

PHYSICAL AND CHEMICAL

PROPERTIES

Flavonoids are crystalline compounds;

They are colored:

• yellow: flavones, flavonoles, chalcones, aurones;

• red: anthocyanidins in acidic media;

• blue: anthocyanidins in alkaline media;

• colorless: catechins, flavans, flavanones,

leucoanthocyanidins, isoflavones.

Flavonoid glycosides are generally soluble in water and

alcohol but insoluble in organic solvents; the aglycones

(genins) are only sparingly soluble in water but soluble

in ether, chloroform.

Under the UV light flavonoids show fluorescence

ofdifferent colors (yellow, orange, brown, red). 14

Certain flavonoids also markedly affect the taste

of foods: for example, some are very bitter and

astringent such as the flavanone glycoside

naringin, which occurs in the peel of grapefruit

(Citrus paradisii). Interestingly. the closely

related compound naringin dihydrochalcone,

which lacks the pyranone ring of naringin, is

exceptionally sweet, being some 1000 times

sweeter than table sugar (sucrose).

15

IDENTIFICATION 1. Chromatographic

identification

Fluorescence under filtered UV light

is used to differentiate different

groups of these compounds as

follows:

AlCl3 gives yellow color (flavones,

flavonoles, chalcones, aurones).

Under the UV light these

compounds show fluorescence of

different colors, e.g.

flavones – green;

Flavonoles – yellowish to yellowish-

green;

Chalcones – brown-pink;

Aurones – pale-brown.

16

1 – rutin, 2 – chlorogenic

acid, 3 – quercetin in

ginkgo leaves samples and

tinctures

2. Shinoda’s test (cyanidin reaction) The alcoholic solution of flavone or flavonol when treated with metallic

magnesium (or Zinc) and hydrochloric acid gives an orange, red or

violet color

3. Wilson’s reaction. Flavonoids form complexes with boric acid which is not destroyed by addition of citric acid alcoholic solution (or oxalic

acid).

OC C

OB

O O

O

O O

OH

OH

OH

OH

17

O

O

OH

O H

O H

O H

O H

OOH

O H

O H

O H

O HO HH

OOH

O H

O H

O H

O H

H +

- H 2 O

+

C l-

Q u e r c e t i n Q u e r c e t i n c h r o m e n o l C y a n i d i n c h l o r i d e

4. A reaction with alkal isolution. Flavonoids

(flavones, flavonoles, chalcones, aurones) when treated

with alkali solution give yellow or orange color.

5. Reaction with iron (III) chloride.

Flavonoids (flavones, flavonoles, chalcones, aurones)

when treated with iron (III) chloride solution give

green or violet color.

6. Reaction with vanillin and concentrated

hydrochloric acid.

Catechins when treated with vanillin solution in

hydrochloric acid give red color.

18

O

O

OH

OH

OH

OH

OH

O

O

OH

OH

OH

OH

ONa

NaOH

OO

O O

OH

OH

OH

OHFe

Cl

OOH

OH O

OH

OH

OH

OH

OOH

OH O

OH

O

O

O

Fe+FeCl3 +FeCl3

Green colour Violet colour

QUANTITATIVE DETERMINATION

Spectrophotometric

High performance liquid chromatography

Gravimetric

Titration

Fluorometric

Polarographic

19

USES

Flavonoids have important dietary significance

because, being phenolic compounds, they are

potent antioxidants.

Many disease states are known to be exacerbated

by the presence of free radicals such as

superoxide and hydroxyl, and flavonoids have the

ability to scavenge and effectively ‘mop up’ these

damaging oxidizing species.

Flavonoids contribute to the diuretic and

diaphoretic action of such drugs as chamomile,

elder flowers, linden blossoms, horsetail and

others

The isoflavone derivatives have a distinct

estrogenic effect.

20

Foods rich in this group of compounds have

therefore been proposed to be important in

ameliorating diseases such as cancer and heart

disease (which can be worsened by oxidation of

low-density lipoprotein); quercetin, a flavonoid

present in many foodstuffs, is a strong

antioxidant. Components of milk thistle (Silybum

marianum), in particular silybin, are

antihepatotoxins; extracts of milk thistle are

generally known as silymarin.

O

OH

OOH

HO

OH

OH

Quercetin

OO

O

HO

OH O

OH

OCH3

OH

OH

Silybin

O

OH

OOH

HO

OH

OH

Quercetin

OO

O

HO

OH O

OH

OCH3

OH

OH

Silybin 21

Literature

1. Pharmacognosy / ed. by prof. Kyslychenko V.S.

Kharkiv/ NUPh, “Zoloti storinky”. – 2011. – 600 p.

2. Trease G.E., Evans W.C. Pharmacognosy. - London;

Philadelphia; Toronto: Sydney; Tokyo; WB Saunders,

1996. - 832 s.

3. Tyler V.E., Brady L.R., Robbers J.E. Pharmacognosy,

9-th ed. - Leo and Fabiger. Philadelphia, 1988.-856 p.

4. British Herbal Pharmacopoeia / British Herbal

Medicine Association.- London, 1996. – 212 p

5. European Pharmacopoeia - Fourth edition. - counsel of

Europe, Strasbourg, 2001

6. Практикум по фармакогнозии: учебное пособие для

студ. вузов / под ред В.Н.Ковалева. – Х: Изд-во

НФАУ, Золотые страницы, 2003. - 512 с.