MEVALONIC ACID PATHWAY

1
MEVALONIC ACID PATHWAY
TERPENES
2
THERE ARE TWO CARBONYL GROUPS IN THE 2-UNIT
POLYKETIDE CHAIN
EITHER ONE CAN REACT
..
1
2
- CO2
LINEAR
BRANCHED
mevalonic acid
POLYKETIDE CHAINS
TERPENES
ACETOGENINS
STEROIDS
3
MEVALONIC ACID PATHWAY
FORMATION OF MEVALONIC ACID FROM ACETYL UNITS
NADPH
3 acetylCoA


..
-
NADPH
H2O
mevalonic acid
(continued next slide)
4
MEVALONIC ACID PATHWAY
The isopentenyl and 3,3-dimethylallyl
pyrophosphate intermediates
ADP AMP
B-Enz
2 ATP
mevalonic acid
These five-carbon intermediates are responsible
for the formation of all the terpenes.
Enz-B
H
IPP
DMAPP
3,3-dimethylallyl pyrophosphate
isopentenyl pyrophosphate
5
TERPENES
6
TERPENES
The Czech chemist Leopold Ruzicka ( born 1887)
showed that many compounds found in nature were
formed from multiples of five carbons arranged
in the same pattern as an isoprene molecule
(obtained by pyrolysis of natural rubber).
natural rubber
head
.
D
C
tail
C C
C
C
isoprene
isoprene unit
He called these compounds terpenes.
7
JOINING ISOPRENE UNITS
individual isoprene units join head-to-tail
Head-to-Tail
an extra bond
Tail-to-Tail
The terms head-to-tail and tail-to-tail are often
used to describe how the isoprene units are
joined.
larger terpenoid units dimerize tail-to-tail
.. explained later
8
TERPENES CAN BE SHOWN TO BE FORMED FROM ISOPRENE
UNITS
head to tail
limonene
diagram showing how two isoprene units combine
to form the limonene skeleton
from lemon and orange peels
9
CLASSIFICATION OF TERPENES
TYPE OF NUMBER OF ISOPRENE TERPENE
CARBON ATOMS UNITS
one
hemiterpene
C5
two
terpene
C10
sesquiterpene
C15
three
diterpene
C20
four
sesterterpene
C25
five
triterpene
C30
six
C40
eight
tetraterpene
NOTE
hemi half di
two sesqui one and a half tri
three tetra four
10
SOME TERPENES (C10)
geraniol
menthol
rose and other flowers
peppermint
a-pinene
camphor
camphor tree
turpentine
11
SESQUITERPENES
guaiazulene
geranium oil
caryophyllene
oil of cloves
12
.. more sesquiterpenes
cedrene
cedar wood oil
longifolene
pine species
13
TRITERPENES
TAIL-TO-TAIL
ambrein
ambergis
14
STEROIDS ARE TRITERPENES (C30)
rearrangements in this area
15
TETRATERPENE
head-to-tail
tail-to-tail
head-to-tail
b-carotene
carrots
16
HOW THE TERPENES ARE FORMED
17
CONCATENATION OF C5 (ISOPRENE) UNITS
DMAPP
IPP
C5
C10
HEAD
C5
B
isopentenyl-PP 3,3-dimethylallyl-PP
C10
TAIL
geranyl-PP
C15
C20
C15
farnesyl-PP
C20
again
geranyl-geranyl-PP
EACH NEW UNIT IS JOINED HEAD-TO-TAIL
18
C30 AND C40 UNITS ARE FORMED DIFFERENTLY
Isoprene
Number
Class of Carbons Units
Origin
HEMITERPENES C5 1 IPP or DMAPP
MONOTERPENES C10 2 geranyl-PP
x2
SESQUITERPENES C15 3 farnesyl-PP
x2
DITERPENES C20 4 geranyl-geranyl-PP
C25 5 uncommon
SESTERTERPENE
TRITERPENES C30 6 2 x (farnesyl-PP)
C35 7 uncommon
TETRATERPENES C40 8 2 x (geranyl-geranyl-PP)
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DIMERIZATION OF C15 AND C20 UNITS
TAIL
rearrange
TAIL
dimerize
Enz-B
H-
NADH
NAD
JOINED SYMMETRICALLY TAIL-TO-TAIL
UNITS ARE JOINED TAIL-TO-TAIL
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COMMON TERPENOID SKELETONS
TERPENES
SESQUITERPENES
HEMITERPENES
C5
C10
C15
DITERPENES
TRITERPENES
C20
C30
21
TERPENOIDS
22
geranial
b-myrcene
geranium oil
hops
geraniol
neral
geranium oil
lemon oil
geranyl-PP (GPP)
linalyl-PP (LPP)
neryl-PP (NPP)
citronellol
rose oil
citronellal
linalool
nerol
a-terprneol
citronella oil
rose oil
coriander oil
23
OPP-
methyl a-terpinyl cation
or

ionize


LPP
1,2-alkyl shift



- H
b-pinene
1,2-alkyl shift
H2O
- H
- H
a-pinene

H2O
borneol
NADP
camphene
NADP
camphor
fenchol
fenchone
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TAXOL
H


()

GGPP
3 100-yr-old trees 1 g
Used clinically in treatment of breast, ovarian,
lung, head, neck cancers.
Phe
acetylCoA
taxadiene
many steps oxidations, esterification
Phe
acetylCoA
paclitaxel
(taxol)
Pacific Yew (bark)
Phe
25
ASSIGNMENTS
Orange Problem
Due in 10 days Wednesday, Nov 14, 2007