Flavonoids

Flavonoids Largest class of the phenolic substances*

Plant pigments (yellow and red)Glycosides are naturally (mostly O-glyc but some C-gly)Differ in:Oxidation stage of the heterocyclic ringDiffer in:1)Substituents (mostly OH or OCH3)2)Nature, position & number of sugar moleculeDiffer in:Occurrence within the plant cell: cytoplasm/cell sap

*(Flavan3-ols [catechins] and flavan 3, 4-diols will be discussed in the chapter of the tannins)

FLAVONOIDS BASIC STRUCTURE

C6-C3-C6 SKELETON(2-Phenyl-γ -chromone)

A

B

O

O

C6

C3

1

2

3456

2'

3'

5'87

6'

4'

C6

Steps in the biosynthesis of the flavonoids

1- Formation of the 15 carbon skeleton2- Modification of the central heterocycle

[oxidation level] (chalcone, aurone, flavonone, flavononol, flavone, flavonol, anthocyanidine)

3- Timing of the substitution in ring B (hydroxylation, methylation)

4-Formation of glycosides (O-glycosides, C-glycosides)

Flavonoids Biosynthesis • Biosynthesized from shikimate (cinnamic acid part) forming

starting molc. & acylpolymalonate (3 acetate residues) pathways. Followed by ring closure.

HO

O

B O

O

O CoAS

-

(Cinnamic Acid Derivative)

Acetate CoA

COOH

O

OOB

+ 3

O

OH

OH

HO

O

O

OH

HO

OH

A

B

Chalcone

Classes of flavonoids• Chalcones• Aurones• Flavonones• Flavononols (Dihydroflavonols)• Flavones• Flavonols• Isoflavones• Biflavonoyls• Flavan-3-ols, flavan-3,4-diols• Anthocyanines• Flavonolignans

Classification Of Flavonoids Based on degree of oxidation & saturation of ring B

I)Phenylchromones:

II) Phenylchromanes:

O

O

Flavanone O

O

OH

Flavanone-3-ol

O

Flavan

O

Flavan-3-ol

OH

O

O1

2

34

56

7

2'8

FlavoneO

O

2'

Flavonol

OH

Flavan 3,4-ol

Classification of Flavonoids III) Chalcones:

IV) 2-Benzylidene coumaranones:

V) Phenylbenzylpyrilliums: (flavylium ion)

VI) Isoflavonoids:

O

OAurones

O

OH

OH

HO+

1 23

4

56

78

1'

2'

3'4'

5'

6'

AnthocyanidinO

O

OH

OH

Isoflavonoid

HO

OChalcone

OH

Anthocyanidines are intensely colored substances (scarlet, blue, purple, red). The anthocyanidins in Hydrangea, colors it RED in acid soil and BLUE in alkali soil. Anthocyanidines are the aglycones while anthocyanines are glycosides of them (anthocyanidine + sugar→anthocyanine)

Role of Flavonoids

• Abundant in plant kingdom• Important chemotaxonomic interest• Minimal medicinal application• Antioxidants• Rutin (flavone aglycone) is known as Vit P =

permeability vit?? (inc. strength of fragile capillaries wall)

• Derivatives of some flavonoids used in pharmaceutical & dietary industries

Ecological importance of the flavonoids

• Pollinating agents• Germination and growth regulation (involved

in IAA/IAA oxidase system of the plants)• Involvement in the biochemistry of sex

determination of the plants• Protection of the plants against attack of

parasites (i.e. fungicidal activity)

RutinExtracted from: • Buds of Sophora japonica (Fabaceae) Indonesian tree• Fagopyrum esculentum (Polygonaceae) seeds• Eucalyptus macrorhyncha leaves (Myrtaceae)• Rutinose= Rhamnosyl-(α1→6)- Glucose

O

O

OH

OH

HO

OH

OR4 35

7

3'4'

Quercetin: R= HRutin : R= -Rhamnosyl-(alpha-1 6)Glucose = (Rutinose)

Naringin & Neohesperidin & Hesperidin• Both are very bitter flavanones• Naringin from grapefruit peel; Citrus paradise (Rutaceae)• Neohesperidin from bitter orange Citrus aurantium peel

(Rutaceae)• Hesperidose = Rhamnose- (α-1→2)-glucose

O

OH

Rha-Glu-O

H

OCH3

OH

O

Neohesperidin

HesperitinNeohesperidose

O

OH

Rha-Glu-O

H

OCH3

OH

O

Hesperidin

Hesperetin

Rutinose= rhamnosyl ( 1-6) glucose

O

O

OH

Naringin

Rutinose-O

Naringin & Neohesperidin Derivatives

• Dihydrochalcones derivatives of naringin & hesperidin are intensely sweet (300-1000 X times as sweet as sucrose).

• Neohesperidin-dihydrochalcone is used as a non sugar sweetening agent.

Isoflavonoids • These compounds are transferred into the body of the

mammalians into estrogen-like compounds affecting the reproduction and usually termed phyto-estrogens.

• Genistein and daidzein were able to prevent the growth of estrogen-receptor positive and negative breast cancer cells in vitro; recently reported; it is progesterone-dependent

• Fabaceae richest source

O

O

OH

OH

Isoflavonoid

HO

Some important isoflavones and rotenones

Genistein(5-OH, 7-OH, 4'-OH) Daidzein(7-OH, 4'-OH)Formonentin (7-OH, 4’-OCH3)

Rotenoids

• Rotenoids take their name from the first known example rotenone

• Common in the Derris and Loncocarpus spp. (Leguminosae)• Piscicidal agents “Lazy fishing”• Classified as natural insecticides • Paralyzing action on insects, with no recoveries• Odorless, stable compounds; biodegradeable• Not recommended for parasite control in human (lice)• Useful in controlling parasites on animals• Used in form of powders or as sprays