Phenolic Compounds

Submitted By:
Rabia Nawaz
(20E-UOC/CHEM58)
Semester 8th
Evening-B
Submitted To:
Mam Samina Shabbir

Natural Product Chemistry

Assignment # __________

Department of Chemistry
University of Chakwal, Chakwal
 Secondary metabolites:
Organic compounds produced by the plants which have no direct role in the growth and
development are called as secondary metabolites.  There are about 100,000 secondary
compounds that are produced by the plants and the structures of more than 15000 alkaloids,
30000 terpenes, several thousand phenyl propanoids, 1000 flavoniods, 500 quinones, 700
polyacetylenes and 800 non-protein amino acids have already been characterised.These
secondary compounds produced by plants are grouped into five major groups.
1. Phenolics
2. Terpenoids
3. Alkaloids
4. Special nitrogen metabolites
5. Cuticular compounds

Phenolic compound:

Phenolic compounds are the secondary metabolites in different fruits, and cereals that contribute
to antioxidant activity. Generally found in fruits, vegetables, olives, grains, coffee beans, and tea
leaves. It has at least one aromatic ring with one or more hydroxyl groups. Depending on how
many phenol units are present in the molecule, it can be categorized as either a simple phenol or
a polyphenol. Numerous biological functions have been assigned to them, with the antioxidant
function being the most significant.

Source of phenolic compound:

According to those studies, the main dietary sources of phenolic compounds include fruits,
vegetables, and drinks. Plant polyphenols may offer dietary antioxidant protection for human
health and disease.

Particularly high in phenolic compounds are cocoa, potato, yam, tomato, kale, Brussels sprouts,
broccoli, and other dark green leafy and colorful vegetables, as well as legumes, cereals, spices,
and fruits like cherries and citrus.

Classification of phenolic compound:

Based on chemical structures, phenolic compounds are divided into the following subclasses:
 1. Phenolic acid

The chemical structure of phenolic acids includes at least one aromatic ring with at least one
hydrogen replaced by a hydroxyl group. They are made up of two groups: hydroxybenzoic acids
(HBAs) and hydroxycinnamic acids (HCAs), which are made from nonphenolic benzoic and
cinnamic acid molecules, respectively. The precursory ingredient for their synthesis is l-
phenylalanine or l-tyrosine, which is done via the shikimate pathway.

2. Flavanoids

The basic building blocks of flavonoid structures are two aromatic rings, A and B, connected by
a three-carbon bridge, which is typically a heterocyclic ring, C. The acetate/malonate pathway,
where ring A is produced, and the shikimate pathway, where ring B is derived from
phenylalanine, are the sources of flavonoid molecules.

The primary flavonoid groups, including flavonols, flavones, flavanones, flavanols (catechins),
isoflavones, flavanonols, and anthocyanidins, are all produced by differences in the substitution
patterns of C rings. The many chemicals within the flavonoids class are produced by variations
in the A and B rings.

Flavonoids are C15 compounds all of which have the structure C 6-C3-C6. Flavonoids may
be grouped into three big classes based on their general structure. In each case, two benzene
rings are linked together by a group of three carbons. It is the arrangement of the C 3 group that
determines how the compounds are classified.
Chalcones:
Chalcones and dihydrochalocones have a linear C 3-chain connecting the two rings. The
C3-chain of chalcones contains a double bond, whereas the C 3-chain of dihydrochalcones is
saturated.
OH OH

B B
HO OH HO OH
β β
A A
α α

OH O OH O

(chalcones) (dihydrochalcones)

Chalcones, such as butein are yellow pigments in flowers. An example of a dihydrochalcone is

phloridzin (phloretin-2′-O-D-glucoside), a compound found in apple leaves, and which has been
reported to have anti-tumor activity (Nelson and Falk, 1993).
OH OH

OH

HO OH HO OH

OH O O O
Glc

(butein) (phloridzin)

Aurones:

Aurones are formed by cyclization of chalcones, whereby the meta-hydroxyl group reacts
with the α-carbon to form a five-member heterocycle. Aurones are also yellow pigments present
in flowers.

OH

HO B
O
A

O
OH

(aurones)
Flavonoids:
Typical flavonoids, such as flavanone, have a six-member heterocycle. Flavonoids have
an A-, B-, and C-ring, and are typically depicted with the A-ring on the left-hand side. The A-
ring originates from the condensation of three malonyl-CoA molecules, and the B-ring
originates from p-coumaroyl-CoA. These origins explain why the A-ring of most flavonoids is
either meta-dihydroxylated or meta-trihydroxylated.
3'
OH
2'
4'
1
B
8 1'
HO O 5'
7 9 2
6'
A C
6 3
10
5 4

OH O
(flavanone)

Isoflavones, isoflavanones and neoflavonoids are also members of the flavonoid group.
They all have the C6-C3-C6 structure but the B-ring is in a different position on the oxygen
heterocycle. Examples are isoflavone and the neoflavonoid dalbergin.

H3CO O O
O

H3CO

(isoflavone) (neoflavonoids)

 Flavanones

The heterocycle of flavanones also contains a ketone group, but there is no unsaturated
carbon-carbon bond. The A- and B-ring can be substituted analogous to the flavones, as in
naringenin.
OH

OH OH

HO O HO O

OH

OH O OH O

(flavanone) (flavanonols)
  Flavanonols

Flavanonols are also known as dihydroflavonols and often occur in association with
tannins in heartwood. An example is taxifolin, also known as dihydroquercitin.
 Leucoanthocyanidins

Leucoanthocyanidins are also referred to as flavan-3,4-cis-diols. They are synthesized

from flavanonols via a reduction of the ketone moiety on C4. Examples are leucocyanidin and
leucodelphinidin. These compounds are often present in wood and play a role in the formation
of condensed tannins.
OH OH

OH OH

HO O HO O
OH

OH OH

OH OH OH OH

(leucocyanidin) (leucodelphinidin)

Because of their completely saturated heterocycle, leucoanthocyanidins, together with

flavan-3-ols are referred to as flavans. Examples of flavan-3ols are catechin and gallocatechin .
The ‘gallo’ in the latter compound refers to the vic-tri-hydroxy substitution pattern on the B-
ring. Unlike most other flavonoids, the flavans are present as free aglycones or as polymers of
aglycones, i.e. they are not glycosylated.
OH OH

OH OH

HO O HO O
OH

OH OH

OH OH

(catec OH (galloc
hin) OH atechi

HO O

O
OH
OH
O
OH

OH

(catechin)
Catechins can also be found as gallic acid esters that are esterified at the 3′ hydroxyl group.
Note the difference between the gallic acid ester of catechin and gallocatechin.

 Flavones
The flavonoids are all structurally derived from the parent substance flavone, which occurs as a
white mealy farina on Primula plants, and all share a number of properties in common.
Flavonoids are mainly water-soluble compounds. They can be extracted with 70% ethanol and
remain in the aqueous layer, following partition of this extract with petroleum ether. Flavonoids
are phenolic and hence change in color when treated with base or with ammonia; thus they are
easily detected on chromatograms or in solution. Flavonoids contain conjugated aromatic
systems and thus show intense absorption bands in the UV and visible regions of the spectrum.
Finally, flavonoids are generally present in plants bound to sugar as glycosides and anyone
flavonoid aglycone may occur in a single plant in several glycosidic combinations. For this
reason, when analysing flavonoids, it is usually better to examine the aglycones present in
hydrolysed plant extracts before considering the complexity of glycosides that may be present in
the original extract. Flavonoids are present in all vascular plants but some classes are more
widely distributed than other; while flavones and flavonols are universal, isoflavones and
biflavonyls are found in only a few plant families.
The heterocycle of flavones contains a ketone group, and has an unsaturated carbon-
carbon bond. Flavones are common in angiosperm.
OH

OH OH

HO O HO O

OH OH

OH O OH O

(kaemferol) OH
( (quercetin)
OH

HO (myricetin)
O
OH

OH

OH O

(myricetin)
  Anthocyanidins and deoxyanthocyandins

The heterocycle of anthocyanidins is a pyrilium kation. Anthocyanidins are typically not

found as free aglycones, with the exception of the following widely distributed, colored
compounds: Pelargonidin (orange-red), cyanidin (red), peonidin (rose-red), delphinidin (blue-
viole), petunidin (blue-purple), and malvidin (purple). A convenient mnemonic is: PCP–DPM.
The most common anthocyanidin is cyanidin. These compounds are present in the vacuoles of
colored plant tissues such as leaves or flower petals. The color of the pigment depends on the
pH, metal ions present, and the combination of substituted sugars and acylesters. Different
colors can also result from the presence of combinations of several anthocyanidins.
OH

OH OH

HO O HO O

OH OH

OH OH

(pelagonidin) (cyanidin)
OCH3 OH

OH OH

HO O HO O
OH

OH OH

OH OH

(peonidin) (delphinidin)
OCH3 OCH3

OH OH

HO O HO O
OH OCH3

OH OH

OH OH

(petunidin) (malvidin)

3. Tannins

Tannins, also known as tannic acid, play an important role in how plants and their ecosystems
interact. For instance, they can act as antimicrobial agents or as a deterrent to herbivores. These
compounds contain a large number of hydroxyl or other functional groups and therefore are
found in the form of esters or heterosis.

4. Coumarins:

The chemical compound coumarin, also known as 2H-chromen-2-one, has the formula C 9H6O2.
In order to form a second six-membered heterocycle that shares two carbons with the benzene
ring, its molecule can be compared to benzene with two neighboring hydrogen atoms swapped
out for a lactone-like chain.

5. Lignans:

Lignans are polyphenolic substances that are present in plants. (Additional details) Many
different plant-based foods, such as seeds, whole grains, legumes, fruit, and vegetables, contain
lignan precursors.
 6. Stilbenes

The broad class of plant secondary metabolites known as stilbenes belongs to the polyphenol
family. They can be found in a variety of food (such as grapes, peanuts, and other foods) and
medicinal plants, such as Polygonum multiflorum, Polygonum cuspidatum (Polygonaceae),
Hopea chinensis (Dipterocarpaceae), Gnetum parvifolium (Gnetaceae), Caragana sinica
(Leguminosae), and Morus alba (Moraceae).

Natural stilbenes, which primarily consist of stilbene monomers, polymers, and heteromers, are
polyhydroxy phenolic substances generated when hydroxyl groups replace hydrogen atoms in
various benzene ring places.
 7. Curcuminoids:

The active components of the dietary spice turmeric, curcuminoids (particularly curcumin), are
derived from the rhizomes of Curcuma longa, a plant that belongs to the ginger family and has
been used medicinally for many years, primarily in Asian countries.

Shikimate pathway:
 Shikimate pathway is an important pathway in plants through which many
secondary plant products are synthesised.
 The key starting materials are phosphoenolpyruvate (PEP) and erythrose 4P
derived from glycolysis and pentose phosphate pathways, respectively.
 These two compounds condense to produce a six carbon cyclic compound with
one carbon (COOH) side chain namely shikimate.
 Then shikimate is phosphorylated and condensed with another molecule of PEP
to produce a cyclic compound containing a three carbon and one carbon side
chains.
 This is finally converted to aromatic amino acids phenylalanine and tyrosine.
  These amino acids are deaminated followed by hydroxylation at different carbon
atoms in the aromatic ring to form cinnamic acid derivatives.
 These cinnamic acid derivatives are utilised for the synthesis of different phenolic
compounds.
Functions of phenolic:
 Phenolics are of great importance as cell wall components.
 They form part of cell wall structures such as lignins, cutins and suberins, which provide
mechanical support and function as barriers against microbial attack.
 The flavonoids and anthocyanins contribute to flower and fruit colours. This is
important for attracting insects and animals to the plant for pollination and seed
dispersal.
 Phenolics also play a defensive role in plants by protecting against predators.
 Simple phenolic acids, polyphenolics like tannins and phenolic resins at the plant
surface are effective feeding deterrents.
 Phenolics are accumulated as post-inflectional low molecular compounds called
phytoalexins as a result of microbial attack.
 Among the phenolic phytoalexins, hydroxycoumarins and hydroxycinnamate conjugates
contribute to disease resistance mechanism in plants.
 Phenolic compounds also produce allopathic effect. A well-known compound from
Juglans species is juglone which is highly toxic for a wide range of plants. It occurs in
the plant as a non-toxic glucoside and is made active by deglucosylation and oxidation
after leaching from the leaves into the soil.
 Phenolic also function as signal molecules in the interaction between nitrogen fixing
bacteria and leguminous plants.
 These plants exude flavonoids which act selectively in Rhizobia as inducers of
nodulation gene transcription.
 Salicylic acid is strongly implicated as a signal molecule which induces active defence
responses in several plant species against many types of pathogens.
 Recently, it has been shown that phenolic compounds function as effective antioxidants.
 Polyphenolics are important in foodstuffs, wines and herbal teas because of their
astringent taste.
 Plants rich in polyphenolics were used as tanning agents in leather industries.
 Phenolic pigments (anthocyanins, flavones etc.) of fruits are most widespread food
colours occurring in fruit juices, wines and jams.
 Anthocyanins have considerable potential in the food industry as safe and effective food
additives.