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Enzymatic Carbon–Carbon Bond Formation 179
HO
H
CH 2 OH
O
H +
OH
2−
CH 2 OPO 3
H
H
H
CHO
OH
OH
OH
2−
CH 2 OPO 3
transketolase
TPP
CH 2 OH
O
CHO HO H
H OH + H OH
2−
CH 2 OPO 3 H OH
H OH
CH 2 OPO 3
2−
Figure 7.29 Example of a transketolase reaction.
lipoamide, which is recycled to oxidised lipoamide by Xavin-dependent lipoamide
dehydrogenase (see Section 6.5).
Thiamine pyrophosphate is also used by several enzymes for carbon–carbon
bond formation. Illustrated in Figure 7.29 is one example of the family of TPPdependent
transketolase enzymes which carry out a range of carbohydrate
2-hydroxyacetyl transfer reactions. A similar mechanism can be written for
these reactions initiated by attack of the thiazolium ylid on the keto group,
followed in this case not by decarboxylation but by carbon–carbon bond
cleavage. The ability of these enzymes to form carbon–carbon bonds enantioselectively
is also being exploited for novel biotransformation reactions that are
of use in organic synthesis.
Carbon–carbon bond formation via carbocation
intermediates
Carbon–carbon bond formation via carbocation (or carbonium ion) intermediates
is less widely found than via carbanion equivalents. However, there is one
large class of biological reactions that involve highly stabilised carbocation ion
intermediates: the conversion of allylic pyrophosphate metabolites into terpenoid
natural products.
7.9 Terpene cyclases
Terpenes are a major class of natural products found widely in plants, but also
including the steroid lipids and hormones found in animals. The common
structural feature of the terpene natural products is the Wve-carbon isoprene
unit. Some common examples shown in Figure 7.30 are plant natural products
menthol, camphor and geraniol.
The biosynthesis of terpenoid natural products proceeds from a family of
allylic pyrophosphates containing multiples of Wve carbon atoms. Two Wvecarbon
units are joined together by the enzyme geranyl pyrophosphate
synthase as shown in Figure 7.31. Loss of pyrophosphate from dimethylallyl