SHIKIMIC ACID PATHWAY

Dr. Md. Rageeb Md. Usman

(M. Pharm., Ph.D., FAPP, FICPHS, FSRHCP, FRSH, FSPER)
Associate Professor
Department of Pharmacognosy

Smt. Sharadchandrika Suresh Patil

College of Pharmacy,
Chopda, Maharashtra, India
 THE SHIKIMIC ACID PATHWAY
This pathway (unique to plants) leads to the formation of the
aromatic amino acids phenylalanine and tyrosine and to the
formation of many other phenyl-C3 compounds.

C C C Phenylpropanoids
Phenyl-C3

Cleavage of the C3 side chain leads to many phenyl-C1 compounds.

C C C C

Phenyl-C1
 GLUCOSE ORIGINS OF THE
pentose SHIKIMIC ACID
phosphate
pathway glycolysis
PATHWAY

Erythrose-4-phosphate PEP
Phosphoenol pyruvate

The pentose phosphate

pathway is one that
Acetyl-CoA converts glucose into
sugars of different sizes
Shikimic Acid (different numbers of C)
by acyl interchanges.
Erythrose is a 4-carbon
sugar.
 FORMATION OF SHIKIMIC ACID

H phosphoenol pyruvate
COOH
O O C
H O COOH
HO P O C CH2
B: H
O CH2 HO
H OH
O
H H+
HO HO P O CH2 HO H
O
H
O
PO CH2 HO H

erythrose-4-phosphate

H+ H+
COOH
HO
COOH COOH COOH O C
CH2
NADPH H
H2C H
OH
HO OH O OH O OH
OH HO H
OH OH H O

shikimic acid
 FORMATION OF CHORISMIC ACID
hydrolysis
of PEP
COOH COOH

ATP

HO OH P O OH CH3
OH OH C O
COOH H+
shikimic acid pyruvic acid

nucleophilic
addition to C=O

COOH COOH :B COOH

- H3PO4 H - H2O
CH2 CH2 CH3
O C P O O C P O O C OH
OH COOH OH COOH OH COOH

chorismic acid
 PREPHENIC ACID
chorismic acid
HOOC
COOH
C
Claisen Type CH2
O C CH Rearrangement
O
2 C O H
H
C OH H O

HO O
OH prephenic acid
pseudoaxial conformation

Prephenic acid can be converted to phenylpyruvic acid

or to 4-hydroxyphenylpyruvic acid:
O
HOOC CH2 C
COOH
NADPH NADP+
p-hydroxy- phenypyruvic
phenylpyruvic -H+ - CO2 -H- -H+ - CO2 -OH acid
H OH
acid

tyrosine phenylalanine
 CLAISEN REARRANGEMENT
A THERMAL REARRANGEMENT

CHR
CHR CHR
H
O
heat
O H+ OH

enolization

an allyl ether an allyl phenol

PREPHENIC ACID TO PHENYLALANINE
HOOC
C
CH2 :B-Enz O
O
C O H CH2 C COOH

H O
- CO2
- H2O phenylpyruvic acid
OH prephenic acid

H+ transamination

CH2 CH COOH
NH2

phenylalanine
 PREPHENIC ACID TO TYROSINE
HOOC
C
O CH2 :B-Enz O
C O H CH2 C COOH

H O
- CO2 HO
NAD+ 4-hydroxyphenyl-
OH prephenic acid pyruvic acid

transamination
hydride transfer
to NAD+

CH2 CH COOH
NH2
HO
tyrosine
PHENYLALANINE AND TYROSINE COME FROM
A COMMON SOURCE AND ARE NOT CONVERTED

PREPHENIC ACID

phenylpyruvic acid 4-hydroxyphenylpyruvic acid

CH2 CH COOH CH2 CH COOH

NH2 X NH2
HO

phenylalanine tyrosine

Although most plants could convert phenylalanine to tyrosine

using hydroxylases, this conversion is a minor pathway. Most
plants make enough tyrosine without converting phenylalanine.
A PRELIMINARY OVERVIEW
Shikimate SHIKIMIC ACID
Pathways
CHORISMIC ACID
(+ acetogenin piece)

PREPHENIC PHENYL-C3
FLAVONOIDS
ACID COMPOUNDS

CINNAMIC
TYROSINE
ACIDS

PHENYLALANINE
PHENYL-C1
COMPOUNDS

ALKALOIDS ALKALOIDS
CINNAMYL COMPOUNDS
 O CINNAMYL COMPOUNDS
CH2 C COOH The rings can have various numbers of hydroxyl
or methoxyl groups (hydroxylases and SAM).

NADPH
O
OH CH CH C H
CH2 C COOH
cinnamaldehyde
H
NADPH
- H2O
O
Enz-SH
CH CH COOH CH CH C S-Enz

oxidative
FADH2 cleavage
cinnamic acid
O
C
CH2 CH2 COOH H
benzaldehyde
hydrocinnamic acid
SOME NATURALLY-OCCURING CINNAMYL COMPOUNDS

COOH COOH COOH COOH COOH

OH OMe HO OMe
OH OH OH OH
CINNAMIC
ACID p-coumaric acid caffeic acid ferulic acid

CH2OH CH2OH CH2OH COOH

corresponding
aldehydes are
also found -
see next slide
OMe MeO OMe MeO OMe
OH OH OH OH

p-coumaryl coniferyl sinapyl sinapic acid

alcohol alcohol alcohol
 TYPICAL REDUCTION SEQUENCES
O O
COOH CH2 OH
C SCoA C H

HSCoA NADPH NADPH

MeO OMe MeO OMe

MeO OMe MeO OMe
OH OH
OH OH
sinapic acid sinapyl aldehyde sinapyl alcohol

COOH CH2OH

estragole
OMe (methylchavicol)

OMe OMe

OMe anethole
 CLEAVAGE TO
PHENYL-C1 COMPOUNDS
 CLEAVAGE TO PHENYL-C1 COMPOUNDS
O O O
COOH C SCoA C SCoA C SCoA
HO O CH2
HSCoA H2O NADP+ C

:S CoA

MeO H
MeO MeO MeO
OH
OH OH OH
ferulic acid
reverse
Claisen
H2O
O O
C OH C SCoA
H COOH H2O
CH2 O
O C H
H
MeO MeO
OH OH
reverse MeO
MeO aldol vanillic acid
OH
OH

vanillin
COUMARINS
 FORMATION OF COUMARINS

COOH COOH

COOH
hydroxylase OH isomerization OH

lactone
(ester)

HO O O
O O

umbelliferone coumarin

HO

HO O O

aesculetin
 DICOUMAROL AND WARFARIN
H
O O O :O O
C C C H C H
SCoA SCoA
.. O O
OH OH

- H2O

O OH

cinnamic acid
O O O O

RODENTICIDE
(rat poison)
OH OH

OH O

O O O O

O O
causes internal dicoumarol
bleeding in cows (sweet clover)
Warfarin
anti-coagulant
FLAVONOIDS

Plant Pigments
 PLANT PIGMENTS
Flavonoids and anthocyanins are conspicuous plant pigments in nature that
are responsible for the beauty and splendor of flowers, fruits, fruit tree blossoms
and of the autumn leaves.

Flavones are responsible for the yellow and orange colors; and the anthocyanins
are the source of red, violet and blue colors. These compounds occur mainly in
higher plants and are less common in the lower orders. You don’t find them in
algae, fungi or bacteria.

The flavonoids play a major role in attracting insects to feed and pollinate these
plants. Some of them also have a bitter taste and repel harmful insects like
caterpillars.

Flavonoids are thought to be antioxidants, and play a major role in our diet,
preventing the ravages of aging caused by free-radicals.

These compound have their biosynthetic origin in both the skimic acid pathway
and the acetogenin pathway - they are of hybrid origin.
shikimic acid
pathway OH
NARINGENIN
CoAS A different starter found in grapefruit
than acetyl-CoA.
O

malonyl-CoA acetogenin
3x pathway

OH OH
O SCoA H
HO O:
O

O O OH O
Michael
internal Claisen addition
and enolizations
OH

HO O
MIXED-ORIGIN A FLAVONE
COMPOUND
flavones are yellow OH O
or orange pigments
naringenin
Anthocyanin
Flower Pigments
Anthocyanin Leaf Pigments
Autumn Leaves

In Spring and Summer

chlorophyll (green) masks
the anthocyanin colors.
 ANTHOCYANIDINS AND ANTHOCYANINS
OH OH OH

HO O HO O HO O
R R R

O2
OH NADPH OH
OH O OH O OH OH

naringenin (R=H)

[O]

OH OH
+ OH
HO O HO O
R R

OH OH
Anthocyanins are - 2 H2 O
red, violet or blue OH OH OH
pigments. pelargonidin (R=H)
cyanidin (R=OH)
plant flower and cyanidin is blue
ANTHOCYANIDINS pelargonidin is pink
leaf pigments
SUMMARY
 (+ acetogenin piece)
Shikimate SHIKIMIC ACID
Pathways FLAVONOIDS

CHORISMIC ACID

PREPHENIC PHENYL-C3 ANTHRANILIC

ACID COMPOUNDS ACID

CINNAMIC
TYROSINE TRYPTOPHAN
ACIDS

PHENYLALANINE NEXT
PHENYL-C1 LECTURE
COMPOUNDS

ALKALOIDS ALKALOIDS ALKALOIDS