CHEMISTRY OF NATURAL PRODUCTS

(professor Manolis Stratakis)

Overview

1. Biosynthesis of terpenes

2. Biosynthesis of phenols

3. Metabolism of fatty acids

4. Metabolism of glucose (glycolysis)

5. Anabolic pathways of fatty acids

and carbohydrates
 Biosynthesis of acyclic terpenoids

From the metabolic pathways

of carbohydrates and fats

Claisen-type Aldol-type
condensation condensation
CH3COSCoA CH3COCH2COSCoA

2 NADPH 2 NADP 3 ATP 3 ADP

O Me

HO OPP
OP
CO2, Pi
Me Isomerization Me
OPP Me OPP Isoprene units

Terpenes
Condensation of isoprene units. Formation of acyclic
terpenes

-H+
OPP OPP OPP
H

OPP

OPP OPP
geranyl OPP farnesyl OPP

OPP
tail-tail dimerization

OPP
geranylgeranyl OPP

squalene
 Formation of monoterpenes (examples)
Me

OH
geraniol Me Me

Me Me OPP
enzyme
OPP

Me Me Me Me

myrcene - OPP

Me Me Me
Me

α-terpinyl cation
limonene

Me CH2
Me Me
Me
O
fenchone Me Me
Me Me
Me α- and β-pinene
Me
Me
camphene Me 3-carene
Me
Formation of sesquiterpenes (examples)

Me

Me bisabolene

Me Me

Me
H
Me Me
cadinene
OPP Me
H
Me Me
Me Me

Me

Me

Me OH carotol
Me
 Formation of diterpenes (examples)

Me

Me
OH

labdadienol
Me Me

Me Me Me Me Me

OPP

Me pimaradiene
geranylgeranyl-OPP Me
Me Me

Me

kaurene
Me Me
 Biosynthesis of squalene

Enz-Nu
Me Me

OPP Me Me
-Enz-Nu
farnesyl-OPP PPO

Me Me
Me Me

Me Me Me Me Me Me Me
Me

PPO

Me Me Me Me Me Me Me Me

NADPH

Me Me Me
Me
Me
Me Me Me
squalene
Biogenesis of steroids and triterpene alcohols (examples)

Me Me Me
Me
Me squalene
Me Me Me

epoxidation
Me
Me
Me
H
Me Me
Me H
HO
Me H Me
+
H O
2,3-epoxysqualene
-H

Me Me
Me H
Me
Me Me Me
Me H Me
Me
Me H HO Lanosterol
Cholesterol Me Me
H H
HO
 Biogenesis of phenols through polyketides

Claisen-type
condensation itteration
CH3COSCoA CH3COCH2COSEnz

O Me O Me
O O O O
Aldol C6-C1
CoA O O HO OH
Me 7 1 S
6 2
polyketide
O OH
Aldol C2-C7 floroacetophenone

OH
O Me
HO Me
hydrolysis
SCoA
orsenilic acid
-H2O COOH
O O
OH
 Biogenesis of phenols: other examples

OH OH
O O O
HOOCCH2COSEnz
CoA
Me S
-CO2
Me O O Me O O

Senz
O

Aldol
Me O Me OH
Senz COOH salicylic acid
O

O O O
CoA OH O O OMe O O
S
methylation Me
Me
O
HO OH MeO OMe
O
Me eugenone
Biogenesis of phenols through shikimic acid. Biosynthesis
of shikimic acid

O OP
OH
COO PO COO
+ PO
O
O HO OH
OH
OH

HO COO COO

-H2O NADPH shikimic acid

O OH HO OH
OH OH
Biosynthesis of aromatic amino acids through shikimic
acid

COO COO OP

+ H
PO COO
O COOH
PO OH PO
OH OH
NH2
COOH
COO OOC COOH

[3,3]-Claisen O phenylalanine

O COOH
OH OH
NH2
chorismic acid prephenic acid
COOH

tyrosine

OH
An overview of catabolic
pathways
Metabolism of fatty
acids
Metabolism of glucose (glycolysis)
Conversion of pyruvate
to acetyl coenzyme A
Anabolism of fatty acids
from CH3COSCoA
Anabolism of glucose
(gluconeogenesis)