Phenolic compound

• embraces a wide range of plant substances which possess in common an aromatic ring bearing
one or more hydroxyl substituent. If the molecule contains two or more hydroxylic groups there
is polyphenols.
• Tend to be water –soluble, since they most frequently occur combined with sugar as glicosides.
Usually located in the cell vacuole
• Among the natural phenolic compounds, of which several thousand structure are known, the
flavonoids form the largest group but simple monocyclic phenols, phenylpropanoids amd
phenolic quinones all exist in plants
• Detecting simple phenol is by means of the intense green, purple, blue or black colours many
of them give in solution when 1% aqueous mixture of 1% ferric chlotide and 1% potassium
feericyanide, is till used as a general means of detecting phenolic compounds on paper
chromatograms.
• Th emajority of phenolic compounds can be detected on chromatograms by their colours of
fluorescences in UV light, the colour is being intensified of changed by fuming the papers with
ammonia vapour
• They are all aromatic show intense absorption in the UV region of the spectrum
 Biosynthesis some natural compounds

p-hydroxycinnamic (p-coumaric) acid

Phenolic Combined forms

acid of hydroxycinnamic
reducing, + malonat acids
dimerization 3 molecules
Acetophenones
polymerisation
Phenilacetate acids
oxidation

Stilbens
Lignans
Lignins Coumarins Phlavonoids
 Phenolic compounds with one benzoic nucleus
Basic skeleton Class Examples
C6 Simple phenols, Benzoquinones Catechol, Hydroquinone, 2,6-
Dimethoxybenzoquinone, phenol, pirocatechol
C6-1 Alkilphenol p-cresol
Phenolic alcohol Saligenin
Phenolic aldehydes Vanilin, Salicylic
Phenolic acids Gallic, salicylic
C6-C2 Acetophenones, Tyrosine 3-Acetyl-6-methoxybenzaldehyde, Tyrosol, p-
derivatives, Phenylacetic acids Hydroxyphenylacetic acid
C6-C3 Hydroxycinnamic acids,
Caffeic, ferulic acids, Myristicin, Eugenol,
Phenylpropenes, Coumarins,
Umbelliferone, aesculetin, Bergenon, Eugenin
Isocoumarins, Chromones
C6-C4 Naphthoquinones Juglone, Plumbagin
 Phenolic compounds with two benzoic nucleus
Basic skeleton Class Examples
C6-C1-C6 Xanthonoids Mangiferin
C6-C2-C6 Stilbenoids, Anthraquinones Resveratrol, Emodin
C6-C3-C6 Chalconoids, Flavonoids, Quercetin, cyanidin, Genistein
Isoflavonoids, Neoflavonoids
(C6-C3)2 Lignans, Neolignans Pinoresinol, Eusiderin,
rosmarinic acid

Polymeric compounds (polyphenols)

(C6-C3)n, Lignins, Raspberry ellagitannin,
(C6)n, Catechol melanins, Tannic acid
(C6-C3-C6)n Flavolans (Condensed tannins),
Polyphenolic proteins,
Polyphenols

The phenolic compounds contributed significantly to th eantioxidant capacity

of the medicinal herbs (Cai et al., 2004)
Nomenclature.
Phenols are usually named as substituted phenols. The
methylphenols are given the special name, cresols. Some other
phenols are named as hydroxy compounds.

OH OH CH3 OH
OH COOH

Br

phenol m-bromophenol o-cresol salicylic acid

OH OH COOH
OH
OH

OH
OH OH

catechol resorcinol hydroquinone p-hydroxybenzoic acid

 Pyrocatechin
Pyrogalol
Hydroquinone
Phenol

Salicine Salidroside
Structure of phenylpropanoids
 3' 3'

Flavonoids Base Structure

8 1
2'

1'
B
4' Flavone
8 1
O
2'

1'
B
4'

5'
O 5'
7 7
2
• Composed of diphenylpropane units C6-
2 6' 6'
A C A C
6 3
C3-C6 6

4
3
5
5

• Eight structural classifications O

• Flavonoids differ through substitution on 3' 3'

the rings Flavanonol

2' 4' Flavonol 2' 4'

B B
• Typically OH or OCH3 groups 8 1
O 1'
5'
8
O
1
1'
5'
7
• Typical to have OH on positions: 7
2 6'
A C
2 6'
A C
• 5 and 7 6 6
OH OH
• 3’, 4’ and 5 5 4 5

O
• Are also present as gylcosides
3'
2' 4'
Flavanone Isoflavone
8 1 B 8 1
1' O
O 5'
7 7
2 6' 2
A C A C 3'
6 6 1'
3 4'
5 5
B
O O 2' 5'

6'
• Istilah flavonoid berasal dari kata flavon yang merupakan salah satu jenis
flavonoid yang terbanyak dan lazim ditemukan (selain flavonol, antosianidin).
• Flavon mempunyai kerangka 2-fenilkroman.
• Berdasarkan tingkat oksidasinya, flavan adalah yang terendah dan digunakan
sebagai induk tatanama flavon.

1 B O
O O
2
A C
3
OH
4
katecin
2-fenilkroman flavan (flavan-3-ol)

OH
O
OH O
leukoantosianidin calkon
dihidrocalkon
(flavan-3,4-diol)
• Biogenesis berasal dari kombinasi antara jalur shikimat dan jalur asetat-mevalonat.
• Merupakan senyawa fenol terbanyak ditemukan di alam.
• Merupakan zat warna merah, ungu, biru, dan sebagian zat warna kuning.
• Kerangka dasar terdiri atas 15 atom karbon yang membentuk susunan C6-C3-C6
• Cincin B flavonoid seringkali mempunyai gugus gugus hidroksil atau alkoksil pada posisi 4’, atau 3’ & 4’.
• Adanya tiga gugus hidroksil atau alkoksil, atau tidak teroksigenasi sama sekali, atau teroksigenasi pada
posisi 2’, sangat jarang ditemukan.
• Hal tersebut disebabkan biogenesis dari flavonoid.
• Glikosida senyawa flavonoid berikatan dengan gula pada gugus hidroksil yang ada.

3
3 A
2
B A 2 1
3
A 1 B
2 B
1

1,3-diarilpropana 1,2-diarilpropana 1,1-diarilpropana

flavonoid isoflavonoid neoflavonoid
• Isoflavonoid dan neoflavonoid hanya ditemukan dalam beberapa jenis
tumbuhan.
isoflavon pterokarpan
• Ragam isoflavonoid:
HO O MeO O

R O O
OH
R=H daidzein O
R = OH genistein pterokarpin

rotenoid
kumestan
R

R2 O O O O
O
R3

R1 O R O
OH OMe
OMe
R1=R3=H R2=OH kumestrol R=H rotenon
R1=R3=OH R2=OMe medelolakton R = OH amorfigenin
• Ragam neoflavonoid:

4-arilkumarin dalbergion

MeO O O
MeO O

HO
O

R1
R1
4-metoksidalbergion
R1=R2=H dalbergin
R1=OH R2=OMe melanein
 Klasifikasi Flavonoid

B
O
Apigenin = trihydroxy 5,7,4’ flavon A C

O Luteolin = tetrahydroxy 5,7,3’,4’ flavon

Flavone

O Ring B O Ring B O Ring B

A 2 2 2
A A
4 3 OH 4 3 OH 3
4
O O O
Flavonol Flavanonol Flavanone

+
O 2
Ring B O 2 Ring B
A 2
A A
3
4 3 Ring B 4 3
4
O O
Isoflavone Chalcone Anthocyanin
15
Quercetin = pentahydroxy 3,5,7,3’,4’ flavonol
Flavonoids Biological Signifcance
• Not all flavonoids have same function in plants
• Anti-fungal
• Insects
• some feeding deterrents/some stimulants
• Antioxidant
• Color: bright colors in plants

PSE 406: Lecture 15 17

Ultraviolet absorption spectra
of Flavonoid

Band I 3000-400 nm
O- Cinnamoyl chromophore
O
O-

Band II: 240-285 nm

Benzoyl chromophore

18
BAND I & BAND II
Band I Band II
1. Flavon 240 - 285 304 - 350
2. Favonol 240 - 285 352 - 385
3. Isoflavon 245 – 270 300 – 340w
4. Flavanon &
Dihidroflavonol 270 – 295 310 – 340w
5. Chalcones 220 – 270m 340 – 390&
6. Aurones 240 – 300m 370 – 430
7. Catechins &
Flavan-3,4-diols ~ 280
8. Antosianin &
Antosianidin 270 – 280m 465 - 550
Pergeseran panjang gelombang absorpsi karena ditambah natrium
metoksida
atau natrium hidroksida
Flavon dan Flavonol

1. Adanya ggs 4’-OH mengakibatkan pita I mengalami pergeseran

batokromik 40-65 nm, tanpa penurunan intensitas.
2. Ggs 3-OH pd flavonol tanpa 4’-OH, pita I juga mengalami pergeseran
batokromik 50-60 nm, disertai penurunan intensitas.
3. Flavonol yang mempunyai 3,4’-OH akan mengalami oksidasi,
sehingga spektrunya mengalami penurunan intensitas dari waktu ke
waktu.
Pengaruh NaOMe/NaOH
(lanjutan)
Isoflavon, flavanon, dan dihidroflavonol
1. Tidak ada pergeseran pd pita II, menandakan tidak adanya ggs hidroksil pada cincin A.
2. Adanya sistem ggs 5,6,7 dan 5,7,8-triOH ditandai dng terjadinya degenerasi spektrum dari
waktu ke waktu.
3. Flavanon dan dihidroflavonol dng ggs 5,7-diOH memberikan pergeseran batokromik pita II
sebesar 35-40 nm dan ggs 7-OH saja sebesar 60 nm.
4. Flavanon tanpa ggs 5-OH, terisomerisasi menjadi calkon dan memberikan puncak pd daerah
400 nm.

Antosianin & Antosianidin

Hanya 3-deoksiantosianidin yang memberikan spektrum yg mantap dlm NaOMe/NaOH, menunjukkan
pergeseran batokromik pita I sebesar 50-60 nm.
Tannins
• Large molecular weight compounds made up of smaller phenolic units
• Characterised by their precipitation reaction with proteins
• Black tea much more astringent than tea with milk due to precipitation of tannin
with milk protein
• Tannins react with saliva proteins
• Molecular weights range from 500 to over 3000
• Act as ‘oxygen’ soaks – assist in preventing oxidation of red wines
• Condensed Tannin
• Epicatechin, Catechin
• Procyanidin, Anthocyanidin
• Leucoanthocyanidin (thru heat & acid)
• Hydrolyzable Tannin
• Gallotannin
• Egallitannin
 Tannins – Condensed or Hydrolysable
• Condensed tannins from grape (skins/seeds)
• Hydrolysable tannins less from grapes but extracted from oak barrels
Hydrolysable tannin structure
Hydrolysable tannins
• Centre of the molecule contains a carbohydrate (often glucose)
• Hydroxyl groups of the carbohydrate are partially or completely
esterified with phenolic units such as gallic or ellagic acids
• Hydrolysable by weak acids or weak bases in the same way simple
ester compounds are, produce the carbohydrate + acid
Condensed Tannins
• Linked units of flavonoid phenolics joined by carbon bonds
• Not hydrolysable
• Usually soluble but very large MW tannins may precipitate
• Generally Chemically stable
 Proanthocyanidins (condensed tannins)
• PAs are more often called condensed tannins due to their condensed chemical structure.
However, HTs also undergo condensation reaction. The term, condensed tannins, is
therefore potentially confusing.
• The term, proanthocyanidins, is derived from the acid catalyzed oxidation reaction that
produces red anthocyanidins upon heating PAs in acidic alcohol solutions.
• The most common anthocyanidins produced are cyanidin (flavan-3-ol, from procyanidin)
and delphinidin (from prodelphinidin)
• PAs may contain from 2 to 50 or greater flavonoid units; PA polymers have complex
structures because the flavonoid units can differ for some substituents and because of the
variable sites for interflavan bonds.
• Anthocyanidin pigments are responsible for the wide array of pink, scarlet, red, mauve,
violet, and blue colors in flowers, leaves, fruits, fruit juices, and wines. They are also
responsible for the astringent taste of fruit and wines.
• PA carbon-carbon bonds are not cleaved by hydrolysis.
• Depending on their chemical structure and degree of polymerization, PAs may or may not
be soluble in aqueous organic solvents.
 OH

AURON OH

HO O
OH
OH

HO
O

C OH
H
OR

O
OH CYANIN (R=glucosyl) (Anthocyanin)
AURON
OH = MARITIMETIN
CYANIDIN (R=H) (Anthocyanidin)

OH
OH

HO O
O

HO

OH O
OH O

BIFLAVONOID
(GINKGETIN)

27
Coumarin Glycosides and Related Compounds
• Coumarins are derivatives of benzo--pyrone, or lactones of o-hydroxycinnamic acid (o-
coumaric acid).
• The parent compound is coumarin, umbelliferone is the 7-OH derivative of Coumrin.
• The glycoside of umbelliferone is called skimmin.
• These compounds are used to protect skin from UV light as they absorb short wave length
(280- 315 nm).
5 4
R1
6 3

7 2
O O R2 O O
8 1
R1=R3=H, R2=OH: Umbeliferon R3
R1=R3=H, R2=OCH3: Herniarin
R1=R2=OH, R3=H: Aeskuletin
R1=OCH3, R2=0H, R3=H: Skopoletin
R1=OCH3, R2=R3=OH: Fraksetin
 Dicoumarol
• It is a phytoalexin formed due to fungal effect on Melilotus officinalis (Red Clover)
• It is a dimer of 4-hydroxycoumarin that is now produced synthetically under the trade
name of Dicoumarol.
• Uses: anticoagulant and rodenticide.
Furanocoumarins
• They are coumarin derivatives with additional furan ring.
• Ammi majus contain a group of furanocoumarins, the parent
compound is called Psoralene.
• They are used for the treatment of psoriases and leucodermia.
LIGNAN
Skeleton results from bonding between the β
carbons of the side chains of two units
derived from 1-phenylpropane (8-8’ bond)
NEOLIGNAN
Also condensation products of
phenylprophaneoid units, but the actual
bond varies and involves no more than one β
carbons (8-3’; 8-1’; 3-3’; 8-O-4’ for example).
 LIGNAN
O
(BERASAL DARI KONIFERILALKOHOL) H3C CH3
CUBEBIN DARI Piper cubeba
OH
O O
O
O
(-) CUBEBIN

• Source: Podophyllum Rhizomes.

• Nature:
• Lignan derivatives.
• Lignans are C18 compounds resulted from condensation of
two hemilignans C9.
• Uses: Anticancer.
Podophyllotoxin
 FLAVANOLIGNAN
Silybum marianum (L.) Gaertn  ASTERACEAE
OH

OH
HO O

CH2OH OCH3

OH

OH O

SILIKRISTIN