It us very wonderful lecture of natural products

1. THE MEVALONATE AND
DEOXYXYLULOSE PHOSPHATE
PATHWAYS: TERPENOIDS AND
STEROIDS
C5 isoprene unit isoprene

2. • Acetyl CoA is the precursor leading to isopentenyl pyrophosphate (IPP)
• Isopentenyl pyrophosphate (IPP) is the universal precursor for all
isoprenoid synthesis
• Initial steps of the pathway: three molecules of acetyl-CoA are fused to
produce the six-carbon (C6) 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA).
• Isopentenyl pyrophosphate is the basic C5 building block for isoprenoid
chain formation.
• Prenyl transferases catalyze head to tail addition of active isoprene
units

4. The basic molecular formulae of terpenes are multiples of that, (C5H8)n where n is
the number of linked isoprene -Isoprene - 2-methyl-1,3-butadiene- units. This is
called the isoprene rule or the C5 rule.
Compounds containing carbon atoms in multiples of 5 suggest a C5 building block -
isoprene units linked in a “head-to-tail” fashion
“Head” - branched end of isoprene and “Tail” -unbranched end of isoprene
2-methyl-1,3-butadiene
4

5. Finding the isoprene building block - cyclic compounds
Finding the isoprene building block - sesquiterpenes (C15)
5

6. Finding the isoprene building block - triterpenes (C30) -
Finding the isoprene building block - tetraterpenes (C40)
Lycopene is responsible for the red color in tomatoes and watermelon
-carotene is the compound that causes carrots and apricots to be orange 6
Lycopene's eleven conjugated double bonds give it its deep red color and are responsible for
its antioxidant activity.

8. Synthesis of Mevalonic acid

9. Synthesis of GPP via IPP and DMAPP

10. Non-mevalonate Pathway for the Synthesis of IPP

12. Synthesis of Monoterpenes
OPP
GPP
OPP OPP
OPP
OPP
H
H
H
H
P-Cymene

14. Synthesis of FPP and GGPP

15. Sesquiterpene

16. Acyclic Diterpenoids
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17 18 19 20

17. Synthesis of Monocyclic Diterpenoids
CH2OPP
H
CH2OPP
CH2OPP
Enz-H GGPP

18. Biosynthesis of Macro cyclic Diterpenoids

19. Synthesis of Bicyclic Diterpenoids

20. Synthesis of Tricyclic Diterpenoids

22. Synthesis of Suqualene, Precursor of Triterpenoids
CH2OPP CH2OPP
Enzyme
Suqualene
FPP
FPP
Enzyme: Squalene synthase

23. Oxidative Cyclization of Suqualene
H
OH
[O]
H
A B
HO
HO
A B
O
A B
H
Squalene
c
b
a
Triterpene
3-Hydroxytriterpene
2,3-Epoxytriterpene

25. HO
H
H
H
H
22
HO
H
23
HO
H
24
H
O
25
H
H
H
HO
H
26
HO
H
27
O
28
H
H
H

28. Non-Oxidative Cyclization of Suqualene
34
H H
H
H H
H
OH
32 33

29. Cyclization of Suqualene from Both Ends
O
H
H
O H
H
HO
H
OH
34
H
H
OH
H
OH
35

30. Biosynthesis of Lanosterol: Precursor of Steroids

31. Biosynthesis of Cholesterol from Lanosterol

32. Carbocations as Intermediates in Terpene Biosynthesis

33. Reactions of Carbocations Atom or Group migration