8/18/2019 Isoprene Rule
1/39
8/18/2019 Isoprene Rule
2/39
Terpenes are natural products that arestructurally related to isoprene.
H2C C
CH3
CH CH2 or or
Isoprene
(2-methyl-1,3-butadiene)
8/18/2019 Isoprene Rule
3/39
Myrcene (isolated from oil of bayberry) isa typical terpene.
CH2
CH3
CH3C CHCH2CH2CCH
CH2
or or
8/18/2019 Isoprene Rule
4/39
An isoprene unit is the carbon skeleton ofisoprene (ignoring the double bonds)
Myrcene contains two isoprene units.
8/18/2019 Isoprene Rule
5/39
The isoprene units of myrcene are joined "head-to-tail."
head tail
tailhead
8/18/2019 Isoprene Rule
6/39
Class Number of carbon atoms
onoterpene ! #es$uiterpene !%
&iterpene '
#esterpene '%
Triterpene
Tetraterpene
Classifcation o Terpenes
8/18/2019 Isoprene Rule
7/39
Representative Monoterpenes
α-Phellandrene
(eucalyptus)
Menthol
(peppermint)
Citral
(lemon grass)
8/18/2019 Isoprene Rule
8/39
a-Selinene (celery)
RepresentativeSesquiterpenes
8/18/2019 Isoprene Rule
9/39
Representative Diterpenes
itamin !itamin !
8/18/2019 Isoprene Rule
10/39
Representative Triterpene
Squalene
(shark liver oil)
tail-to-tail linkage of isoprene units
8/18/2019 Isoprene Rule
11/39
C15 sesquiterpenoids are derived from farnesyl diphosphate
!hich consists of three C5 "isoprene units# that are $oined
"head-to-tail#
OPP
C%& diterpenoids are derived from geranyl diphosphate
!hich consists of four C5 "isoprene units# that are $oined
"head-to-tail#
OPP
8/18/2019 Isoprene Rule
12/39
C%5 sesterpenoids are derived from geranyl farnesyl
diphosphate !hich consists of five C5 "isoprene units# that
are $oined "head-to-tail#
C'& triterpenoids and steroids are derived from squalene
!hich consists of t!o C15 farnesyl units# that are $oined "tail-
to-tail#
C& tetraterpenoids are derived from phytocene !hich
consists of t!o C%& geranylgeranyl units# that are $oined "tail-
to-tail#
OPP
8/18/2019 Isoprene Rule
13/39
8/18/2019 Isoprene Rule
14/39
he isoprene units in terpenes do notcome from isoprene*
hey come from isopentenyl pyrophosphate*
+sopentenyl pyrophosphate (5 car,ons)
comes from acetate (% car,ons) viamevalonate ( car,ons)*
8/18/2019 Isoprene Rule
15/39
CH3C"H
"
3 H"CCH2CCH2CH2"H
CH3
"H
"
Me#alonic acid
H2C CCH2CH2"$"$"H
CH3 " "
Isopentenyl pyrophosphate
8/18/2019 Isoprene Rule
16/39
.imethylallyl pyrophosphate has a leaving group(pyrophosphate) at an allylic car,on/ it is reactiveto!ard nucleophilic su,stitution at this position*
Isopentenyl pyrophosphate is intercon#ertible to
dimethylallyl pyrophosphate.
Isopentenyl pyrophosphate Dimethylallyl pyrophosphate
8/18/2019 Isoprene Rule
17/39
8/18/2019 Isoprene Rule
18/39
The key process in*ol*es the doublebond of isopentenyl pyrophosphate
acting as a nucleophile to+ard the allyliccarbon of dimethylallyl pyrophosphate.
%%
8/18/2019 Isoprene Rule
19/39
&OPP %
8/18/2019 Isoprene Rule
20/39
The carbocationcan lose aproton to gi*e adouble bond.
8/18/2019 Isoprene Rule
21/39
The carbocationcan lose aproton to gi*e adouble bond.
H & %
8/18/2019 Isoprene Rule
22/39
This compound is called geranylpyrophosphate. ,t can undergo hydrolysis ofits pyrophosphate to gi*e geraniol (rose oil).
8/18/2019 Isoprene Rule
23/39
0eraniol
%2
8/18/2019 Isoprene Rule
24/39
8/18/2019 Isoprene Rule
25/39
H & %
8/18/2019 Isoprene Rule
26/39
This compound is called farnesylpyrophosphate.
ydrolysis of the pyrophosphateester gi*es the alcohol farnesol.
8/18/2019 Isoprene Rule
27/39
arnesyl pyrophosphate is e/tendedby another isoprene unit by reaction
+ith isopentenyl pyrophosphate.
8/18/2019 Isoprene Rule
28/39
0ings form by intramolecularcarbon-carbon bond formation.
E E doubledouble
bondbondZ Z doubledouble
bondbond
8/18/2019 Isoprene Rule
29/39
H & %
H2"
'imonene
α-erpineol
8/18/2019 Isoprene Rule
30/39
β -Pinene
%
α-Pinene
8/18/2019 Isoprene Rule
31/39
8/18/2019 Isoprene Rule
32/39
CH3C"H
"
3 H"CCH2CCH2CH2"H
CH3
"H
"
Me#alonic acid
H2C CCH2CH2"$"$"H
CH3 " "
Isopentenyl pyrophosphate
8/18/2019 Isoprene Rule
33/39
,n a se$uence analogous to the earlysteps of fatty acid biosynthesis1 acetylcoen2yme A is con*erted to S-
acetoacetyl coen2yme A.
CHCH33CCHCCH22CCo!CCo!
""""
S S -!cetoacetyl-!cetoacetyl
coen*yme !coen*yme !
8/18/2019 Isoprene Rule
34/39
,n the ne/t step1 #-acetoacetyl coen2yme Areacts +ith acetyl coen2yme A.
Nucleophilic addition of acetyl coen2yme A(probably *ia its enol) to the ketonecarbonyl of S-acetoacetyl coen2yme Aoccurs.
CHCH33CCo!CCo!
""
%%CHCH33CCHCCH22CCo!CCo!
""""
8/18/2019 Isoprene Rule
35/39
CH3CCo!
"
CH3CCH2CCo!
CH2C"H
H" "
"
%CH3CCH2CCo!
""
8/18/2019 Isoprene Rule
36/39
Ne/t1 the acyl coen2yme A functionis reduced.
The product of this reduction isme*alonic acid.
CH3CCH2CCo!
CH2C"H
H" "
"
8/18/2019 Isoprene Rule
37/39
CH3CCH2CCo!
CH2C"H
H" "
"
CH3CCH2CH2"H
CH2C"H
H"
"
Me#alonic
acid
8/18/2019 Isoprene Rule
38/39
The t+o hydro/yl groups of me*alonicacid undergo phosphorylation.
CH3CCH2CH2"H
CH2C"H
H"
"
CH3CCH2CH2"$$
CH2C"H
"
"$"32&
8/18/2019 Isoprene Rule
39/39
3hosphorylation is follo+ed by a no*elelimination in*ol*ing loss of C4' and 345.
CH3CCH2CH2"$$
CH2
"$"33&
CH3CCH2CH2"$$
CH2
"
"$"32&
C "++
++++
&
" C "
Isopentenyl
Pyrophosphate