100
STEREOCHEMISTRY
phases for column chromatography. This allows simple chromatographic separation of enantiomers. In practice it is effectively the same principle, that of forming
diastereoisomeric complexes with the chiral material
comprising the column. One enantiomer binds more
tightly than the other and, therefore, passes through the
column at a different rate. The two enantiomers thus
emerge from the column as separate fractions.
It has also proved possible to exploit the enantiospecific properties of enzymes to achieve resolution of a
racemic mixture during a chemical synthesis. Enzymes
(see Section 13.4) are proteins that catalyse biochemical reactions with outstanding efficiency and selectivity.
This is a consequence of the size and shape of the
enzyme’s binding site, a feature that is determined by
the sequence of amino acid residues in the protein (see
Section 13.3.2). The selectivity of enzymes means that
they carry out reactions on one functional group in the
presence of others that might be affected by a chemical
reagent. It also means that they can be stereoselective,
either performing reactions in a stereospecific manner or
only reacting with substrates with a particular chirality.
As a simple example, racemic ester structures may be
resolved by the use of ester hydrolysing enzymes called
lipases.
With the appropriate choice of enzyme, it has been
found that only one enantiomer of the racemic mixture
is hydrolysed, whilst the other remains unreacted. It is
then a simple matter to separate the unreacted ester
from the alcohol. The unreacted ester may then be
hydrolysed chemically, thus achieving resolution of the
enantiomeric alcohols.
3.4.9 Fischer projections
Fischer projections provide a further approach to the
two-dimensional representations of three-dimensional
formulae. They become particularly useful for molecules
that contain several chiral centres, and are most
frequently encountered in discussions of sugars (see
O
A
C
B
O
A
C
B
+
racemic ester
Me
O
Me
O
lipase
HO
A
C
B
O
A
C
B
+
Me
O
only one enantiomer
is hydrolysed
base
HO
A
C
B
separate
HO
A
C
B
O
A
C
B
Me
O
Section 12.2). To start, though, let us consider just one
chiral centre, and choose the amino acid we met earlier
(see Section 3.4.2), (−)-(S)-serine.
The Fischer projection is drawn with groups on
horizontal and vertical lines, but without showing the
chiral carbon atom. Should you put in this carbon
atom, it can no longer be considered that you are
representing stereochemistry. The Fischer projection
then implies that horizontal bonds are wedged, whilst
vertical bonds are dotted, and it thus speeds up the
drawing of stereochemical features. For (−)-(S)-serine,
the wedge–dot version is what one would see if
one looked down on the right-hand stereostructure
CH 2 OH
CO 2 H
H 2 N
H
H 2 N
H
CH 2 OH
CO 2 H
H 2 N
H
HOH 2 C CO 2 H
(–)-(S)-serine
≡
longest carbon
chain vertical
carbon not shown −
intersection of lines
horizontal lines above plane
vertical lines below plane
≡
Fischer projection
Fischer projection is equivalent to
viewing molecule from the top
carbon with highest
oxidation state at top
STEREOCHEMISTRY
phases for column chromatography. This allows simple chromatographic separation of enantiomers. In practice it is effectively the same principle, that of forming
diastereoisomeric complexes with the chiral material
comprising the column. One enantiomer binds more
tightly than the other and, therefore, passes through the
column at a different rate. The two enantiomers thus
emerge from the column as separate fractions.
It has also proved possible to exploit the enantiospecific properties of enzymes to achieve resolution of a
racemic mixture during a chemical synthesis. Enzymes
(see Section 13.4) are proteins that catalyse biochemical reactions with outstanding efficiency and selectivity.
This is a consequence of the size and shape of the
enzyme’s binding site, a feature that is determined by
the sequence of amino acid residues in the protein (see
Section 13.3.2). The selectivity of enzymes means that
they carry out reactions on one functional group in the
presence of others that might be affected by a chemical
reagent. It also means that they can be stereoselective,
either performing reactions in a stereospecific manner or
only reacting with substrates with a particular chirality.
As a simple example, racemic ester structures may be
resolved by the use of ester hydrolysing enzymes called
lipases.
With the appropriate choice of enzyme, it has been
found that only one enantiomer of the racemic mixture
is hydrolysed, whilst the other remains unreacted. It is
then a simple matter to separate the unreacted ester
from the alcohol. The unreacted ester may then be
hydrolysed chemically, thus achieving resolution of the
enantiomeric alcohols.
3.4.9 Fischer projections
Fischer projections provide a further approach to the
two-dimensional representations of three-dimensional
formulae. They become particularly useful for molecules
that contain several chiral centres, and are most
frequently encountered in discussions of sugars (see
O
A
C
B
O
A
C
B
+
racemic ester
Me
O
Me
O
lipase
HO
A
C
B
O
A
C
B
+
Me
O
only one enantiomer
is hydrolysed
base
HO
A
C
B
separate
HO
A
C
B
O
A
C
B
Me
O
Section 12.2). To start, though, let us consider just one
chiral centre, and choose the amino acid we met earlier
(see Section 3.4.2), (−)-(S)-serine.
The Fischer projection is drawn with groups on
horizontal and vertical lines, but without showing the
chiral carbon atom. Should you put in this carbon
atom, it can no longer be considered that you are
representing stereochemistry. The Fischer projection
then implies that horizontal bonds are wedged, whilst
vertical bonds are dotted, and it thus speeds up the
drawing of stereochemical features. For (−)-(S)-serine,
the wedge–dot version is what one would see if
one looked down on the right-hand stereostructure
CH 2 OH
CO 2 H
H 2 N
H
H 2 N
H
CH 2 OH
CO 2 H
H 2 N
H
HOH 2 C CO 2 H
(–)-(S)-serine
≡
longest carbon
chain vertical
carbon not shown −
intersection of lines
horizontal lines above plane
vertical lines below plane
≡
Fischer projection
Fischer projection is equivalent to
viewing molecule from the top
carbon with highest
oxidation state at top