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Flavonoids
Prepared by
Dr. N.GOPINATHAN
ASSISTANT PROFESSOR
DEPARTMENT OF PHARMACEUTICAL CHEMISTRY
FACULTY OF PHARMACY
SRIHER [DU]
CHENNAI-116
TAMILNADU
Introduction
• Flavonoids consist of a large group of
polyphenolic compounds belong to a class
of plant secondary metabolites having a
benzo-𝛾-pyrone structure and are
ubiquitously present in plants, fruits,flowers
vegetables and certain beverages..
• They are synthesized by phenylpropanoid
pathway.
• It is derived from latin word flavus meaning
yellow.
Use
Flavonoids are associated with a broad
spectrum of health-promoting effects
and are an indispensable component
in a variety of nutraceutical,
pharmaceutical, medicinal and
cosmetic applications.
HISTORY
• Flavonoids are a group of natural compounds with
variable phenolic structures and are found in plants.
• In 1930 a new substance was isolated from oranges.
• At that time it was believed to be a member of a new
class of vitamins and was designated as vitamin P.
• Later on it became clear that this substance was a
flavonoid (rutin)
• Till now more than4000 varieties of flavonoids have
been identified
Subgroups of Flavonoids
• Chalcones,
• Flavones,
• Flavonols
• Isoflavones.
Basic skeleton of flavonoids
Classification
Flavonoids can be subdivided into
different subgroups depending on
the carbon of the C ring on which
the B ring is attached and the
degree of unsaturation and
oxidation of the C ring
Classification
• Flavonoids in which the B ring is linked in position
3 of the C ring are called isoflavones.
• Those in which the B ring is linked in position 4
are called neoflavonoids,
• while those in which the B ring is linked in
position 2 can be further subdivided into several
subgroups on the basis of the structural features
of the C ring. These subgroups are: flavones,
flavonols, flavanones, flavanonols, flavanols or
catechins, anthocyanins and chalcones
Chalcone
Anthocyanins
Flavonols
Isoflavones
Flavones
Flavonols
• In plants, flavonoids are synthetized via phenyl
propanoid biosynthetic pathway and their
structural feature is a 2-phenyl-benzo-γ-pyrane
nucleus including two aromatic rings (A and B
rings) and a pyran heterocyclic ring (C ring).
• The A-ring originates from the cyclization of 3
molecules of malonyl CoA and it is linked to B-
ring, derived from phenylalanine, by a three-
carbon bridge (C-ring).
Flavones
• They have a double bond between positions 2
and 3
• A ketone in position 4 of the C ring.
• Most flavones have a hydroxyl group in
position 5 of the A ring,
• while hydroxylation in other positions, for the
most part in position 7 of the A ring or 3′ and
4′ of the B ring
Special Characteristics of Flavonoids:
• Flavonoids are one of the most essential non-
nitrogenous plant pigments.
• It is responsible for flower coloration by
producing yellow or red/blue pigmentation in
shoots, leaves, buds, petals, and fruits.
• This pigmentation is to attract pollinators to the
flowers.
• In some types of plants, flavonoids are involved in
UV filtration, symbiotic nitrogen fixation and
floral pigmentation.
UV spectra of flavonoids
Spectral Characteristics of Flavonoids.
• Studies on flavonoids by spectroscopy have
revealed that most flavones and flavonols
exhibit two major absorption bands:
• Band I (320–385nm) represents the B ring
absorption, while
• Band II (250–285 nm) corresponds to the A
ring absorption.
UV spectra of flavonoids
Benzoyl Cinnamoyl
Band I and Band II reason
Band I peak in the 450-560 nm
region due to hydroxyl
cinnamoyl system of the B ring
and Band II peaks in the 240-
280 nm region due to the
benzoyl system of the A ring
Biogenesis of flavone
• From the biogenetic point of view the C15
carbon frame work of flavonoid can be divided
into two parts, one part consisting of six
carbon atoms which form the ring A.
• The other part consisting of nine carbon
atoms known as phenyl propanoid moiety.
• Ring A by acetate or polyketide route
• Ring B by shikimate pathway.
Biosynthesis of flavonoid
Structural Elucidation of flavone
O
O
Molecular formula of flavone
C15H10O2
Absence of hydroxyl group
• Acetylation
• Oxidation
• Revealed that flavone does not possess any
hydroxyl group.
Structure of flavone
• Upon fusion with potassium hydroxide flavone
yields phenol and benzoic acid.
O
O
KOH
Fusion
OH
+
O OH
Upon boiling with alcoholic KOH flavone yields a
mixture of four compounds salicylic acid,
acetophenone, o- hydroxy acetophenone and benzoic
acid
Structural elucidation of
isoflavone
Isoflavone
Molecular formula
• It is determined first
Presence of hydroxyl group and
methoxyl group
• Oxidation
• Acetylation
• Zerewitinoff determination
• Zeisel,’s reaction
Zerewitinoff determination
The Zerewitinoff determination or Zerevitinov
determination is a quantitative chemical test for
the determination of active hydrogens in
a chemical substance. A sample is treated with
the Grignard reagent, methylmagnesium iodide,
which reacts with any acidic hydrogen atom to
form methane. This gas can be determined
quantitatively. For example:
Zerewitinoff determination
Zeisel’s reaction
• Zeisel test is a chemical test for the presence
of esters or ethers in a chemical substance.
• In a qualitative test a sample is first reacted
with a mixture of acetic acid and hydrogen
iodide in a test tube.
• The ensuing reaction results in the cleavage of
the ether or the ester into an alkyl iodide and
respectively an alcohol or a carboxylic acid.
• By heating this mixture, the gases are allowed to come
into contact with a piece of paper higher up the test
tube saturated with silver(II) nitrate. Any alkyl iodide
present will give a reaction with the mercury
compound to silver (II) iodide which has a red or yellow
color.
• The reaction can also be used to determine the
number of methoxy (-OCH3) groups,by distilling the
iodomethane into a solution of silver nitrate, which
precipitates silver iodide. By filtering and weighing this
precipitate it is possible to calculate the number
of iodine atoms and hence methoxy groups.
Zeisel’s reaction
Reaction of isoflavone with KOH
alc.KOH
Boiling
O
O
OH
OH
+
OH
O
OH
Alc.KOH
O
OH
H +
O
OH OH
OH
Formic acid
P-hydroxy phenyl acetic acid
Resorcinol
P hydroxy phenyl acetic acid
References
• Shashank Kumar and Abhay K. Pandey
Chemistry and Biological Activities of
Flavonoids: An Overview Hindawi Publishing
Corporation The ScientificWorld Journal
Volume 2013, Article ID 162750, 16 pages
• http://dx.doi.org/10.1155/2013/162750.
• Prithviraj Karak BIOLOGICAL ACTIVITIES OF
FLAVONOIDS: AN OVERVIEW Karak, IJPSR,
2019; Vol. 10(4): 1567-1574.
• Pharmaceutical chemistry of natural product
by V.Alagarsamy Elsevier page no: 427-438.
• Chemistry of natural product by S.V.Bhat
Narosa publication 585

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Flavonoids

  • 1. Flavonoids Prepared by Dr. N.GOPINATHAN ASSISTANT PROFESSOR DEPARTMENT OF PHARMACEUTICAL CHEMISTRY FACULTY OF PHARMACY SRIHER [DU] CHENNAI-116 TAMILNADU
  • 2. Introduction • Flavonoids consist of a large group of polyphenolic compounds belong to a class of plant secondary metabolites having a benzo-𝛾-pyrone structure and are ubiquitously present in plants, fruits,flowers vegetables and certain beverages.. • They are synthesized by phenylpropanoid pathway. • It is derived from latin word flavus meaning yellow.
  • 3. Use Flavonoids are associated with a broad spectrum of health-promoting effects and are an indispensable component in a variety of nutraceutical, pharmaceutical, medicinal and cosmetic applications.
  • 4. HISTORY • Flavonoids are a group of natural compounds with variable phenolic structures and are found in plants. • In 1930 a new substance was isolated from oranges. • At that time it was believed to be a member of a new class of vitamins and was designated as vitamin P. • Later on it became clear that this substance was a flavonoid (rutin) • Till now more than4000 varieties of flavonoids have been identified
  • 5. Subgroups of Flavonoids • Chalcones, • Flavones, • Flavonols • Isoflavones.
  • 6. Basic skeleton of flavonoids
  • 7. Classification Flavonoids can be subdivided into different subgroups depending on the carbon of the C ring on which the B ring is attached and the degree of unsaturation and oxidation of the C ring
  • 8. Classification • Flavonoids in which the B ring is linked in position 3 of the C ring are called isoflavones. • Those in which the B ring is linked in position 4 are called neoflavonoids, • while those in which the B ring is linked in position 2 can be further subdivided into several subgroups on the basis of the structural features of the C ring. These subgroups are: flavones, flavonols, flavanones, flavanonols, flavanols or catechins, anthocyanins and chalcones
  • 15. • In plants, flavonoids are synthetized via phenyl propanoid biosynthetic pathway and their structural feature is a 2-phenyl-benzo-γ-pyrane nucleus including two aromatic rings (A and B rings) and a pyran heterocyclic ring (C ring). • The A-ring originates from the cyclization of 3 molecules of malonyl CoA and it is linked to B- ring, derived from phenylalanine, by a three- carbon bridge (C-ring).
  • 16. Flavones • They have a double bond between positions 2 and 3 • A ketone in position 4 of the C ring. • Most flavones have a hydroxyl group in position 5 of the A ring, • while hydroxylation in other positions, for the most part in position 7 of the A ring or 3′ and 4′ of the B ring
  • 17. Special Characteristics of Flavonoids: • Flavonoids are one of the most essential non- nitrogenous plant pigments. • It is responsible for flower coloration by producing yellow or red/blue pigmentation in shoots, leaves, buds, petals, and fruits. • This pigmentation is to attract pollinators to the flowers. • In some types of plants, flavonoids are involved in UV filtration, symbiotic nitrogen fixation and floral pigmentation.
  • 18. UV spectra of flavonoids
  • 19. Spectral Characteristics of Flavonoids. • Studies on flavonoids by spectroscopy have revealed that most flavones and flavonols exhibit two major absorption bands: • Band I (320–385nm) represents the B ring absorption, while • Band II (250–285 nm) corresponds to the A ring absorption.
  • 20. UV spectra of flavonoids Benzoyl Cinnamoyl
  • 21. Band I and Band II reason Band I peak in the 450-560 nm region due to hydroxyl cinnamoyl system of the B ring and Band II peaks in the 240- 280 nm region due to the benzoyl system of the A ring
  • 22. Biogenesis of flavone • From the biogenetic point of view the C15 carbon frame work of flavonoid can be divided into two parts, one part consisting of six carbon atoms which form the ring A. • The other part consisting of nine carbon atoms known as phenyl propanoid moiety. • Ring A by acetate or polyketide route • Ring B by shikimate pathway.
  • 23.
  • 24.
  • 27. O O
  • 28. Molecular formula of flavone C15H10O2
  • 29. Absence of hydroxyl group • Acetylation • Oxidation • Revealed that flavone does not possess any hydroxyl group.
  • 30. Structure of flavone • Upon fusion with potassium hydroxide flavone yields phenol and benzoic acid. O O KOH Fusion OH + O OH
  • 31. Upon boiling with alcoholic KOH flavone yields a mixture of four compounds salicylic acid, acetophenone, o- hydroxy acetophenone and benzoic acid
  • 34. Molecular formula • It is determined first
  • 35. Presence of hydroxyl group and methoxyl group • Oxidation • Acetylation • Zerewitinoff determination • Zeisel,’s reaction
  • 36. Zerewitinoff determination The Zerewitinoff determination or Zerevitinov determination is a quantitative chemical test for the determination of active hydrogens in a chemical substance. A sample is treated with the Grignard reagent, methylmagnesium iodide, which reacts with any acidic hydrogen atom to form methane. This gas can be determined quantitatively. For example:
  • 38. Zeisel’s reaction • Zeisel test is a chemical test for the presence of esters or ethers in a chemical substance. • In a qualitative test a sample is first reacted with a mixture of acetic acid and hydrogen iodide in a test tube. • The ensuing reaction results in the cleavage of the ether or the ester into an alkyl iodide and respectively an alcohol or a carboxylic acid.
  • 39. • By heating this mixture, the gases are allowed to come into contact with a piece of paper higher up the test tube saturated with silver(II) nitrate. Any alkyl iodide present will give a reaction with the mercury compound to silver (II) iodide which has a red or yellow color. • The reaction can also be used to determine the number of methoxy (-OCH3) groups,by distilling the iodomethane into a solution of silver nitrate, which precipitates silver iodide. By filtering and weighing this precipitate it is possible to calculate the number of iodine atoms and hence methoxy groups.
  • 41. Reaction of isoflavone with KOH alc.KOH Boiling O O OH OH + OH O OH Alc.KOH O OH H + O OH OH OH Formic acid P-hydroxy phenyl acetic acid Resorcinol P hydroxy phenyl acetic acid
  • 42. References • Shashank Kumar and Abhay K. Pandey Chemistry and Biological Activities of Flavonoids: An Overview Hindawi Publishing Corporation The ScientificWorld Journal Volume 2013, Article ID 162750, 16 pages • http://dx.doi.org/10.1155/2013/162750. • Prithviraj Karak BIOLOGICAL ACTIVITIES OF FLAVONOIDS: AN OVERVIEW Karak, IJPSR, 2019; Vol. 10(4): 1567-1574.
  • 43. • Pharmaceutical chemistry of natural product by V.Alagarsamy Elsevier page no: 427-438. • Chemistry of natural product by S.V.Bhat Narosa publication 585