Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

180 Chapter 7
O
OH
OH
camphor
geraniol
menthol
Figure 7.30 Terpenoid natural products.
DMAPP
+
+
OPP OPP OPP
IPP
H H
− BEnz
+
farnesyl PP
OPP
Figure 7.31 Biosynthesis of farnesyl pyrophosphate.
IPP
geranyl PP
OPP
pyrophosphate (DMAPP) generates a stabilised allylic carbonium ion. Attack
of the p-bond of isopentenyl pyrophosphate (IPP) generates a tertiary carbocation.
StereospeciWc loss of a proton generates the product geranyl pyrophosphate.
Similar reactions with further units of IPP generate the C 15 building
block farnesyl pyrophosphate, the C 20 geranylgeranyl pyrophosphate, and
so on.
Geranyl pyrophosphate is converted to the family of C 10 monoterpenes
by the monoterpene cyclases. A 96-kDa cyclase enzyme responsible for the
assembly of (þ)-a-pinene has been puriWed from sage leaves, whilst a separate
55-kDa enzyme from the same source catalyses the production of the opposite
enantiomer ( )-a-pinene. The 55-kDa cyclase II produces several other
isomeric products. As well as ( )-a-pinene (26%) the enzyme produces
( )-b-pinene (21%), ( )-camphene (28%), myrcene (9%) and ( )-limonene
(8%). These products can be rationalised by the mechanism shown in Figure
7.32. It has been shown that the Wrst step in the assembly of these monoterpenes
is a 1,3-migration of pyrophosphate to give linalyl pyrophosphate, which for
cyclase II has the 3S stereochemistry. Loss of pyrophosphate gives an allylic
cation, which is attacked by the second alkene to give a six-membered ring and
a tertiary carbocation intermediate. Further ring closure to generate a fourmembered
ring gives another tertiary carbocation, which can deprotonate in
either of two ways to give a-pinene or b-pinene. Limonene can be formed by