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194 Chapter 8
C-O
cleavage
H
E1
H
C-H
cleavage
E1cb
OH
OH
B −
concerted
elimination
H
OH
Figure 8.2 Mechanisms for elimination of water.
E2
determines the type of elimination mechanism involved, as illustrated in Figure
8.2. If C2O cleavage takes place Wrst, a carbonium ion is generated which
eliminates via cleavage of an adjacent C2H bond. This E1 mechanism is found
in organic reactions, but is rare in biological systems. If C2H bond cleavage
occurs Wrst a carbanion intermediate is generated, which eliminates via subsequent
C2O bond cleavage. This E1cb mechanism is quite common in biological
chemistry in cases where the intermediate carbanion is stabilised, as in the
elimination of b-hydroxy-ketones or b-hydroxy-thioesters. If C2O and C2H
bond cleavage are concerted then a single-step E2 mechanism is followed.
The stereochemical course of enzymatic elimination reactions is strongly
dependent upon the mechanism of elimination. If an E2 mechanism is operating
then an anti-elimination will ensue. This is generally observed in the enzymecatalysed
dehydrations of b-hydroxy-carboxylic acids. However, if an E1cb
elimination mechanism is operating then the stereochemistry of the reaction
can either be syn- or anti- depending upon the positioning of the catalytic
groups at the enzyme active site. Commonly the syn- stereochemistry is observed
for enzyme-catalysed elimination of b-hydroxy-ketones, although this is
not true in all cases.
8.2 Hydratases and dehydratases
Enzymes that catalyse the elimination of water are usually known as dehydratases.
However, since addition/elimination reactions are reversible, sometimes
the biologically relevant reaction is the hydration of an alkene, in which case the
enzyme would be known as a hydratase. We shall consider in turn enzymes
which catalyse the elimination of b-hydroxy-ketones, b-hydroxy-thioesters and
b-hydroxy-carboxylic acids.
The dehydration of 3-dehydroquinic acid to 3-dehydroshikimic acid shown
in Figure 8.3 is a well-studied example of an enzyme-catalysed elimination of a