Chemistry Reference
In-Depth Information
Box 3.7 (continued)
receptor for chiral
part of molecule
chiral
centre
X
X
Y
Y
A
A
Z
Z
receptor for achiral
part of molecule
If binding to the receptor involves the chiral centre, then we may see activity in only one enantiomer, but if binding
does not involves the chiral centre, then there may be similar activities for each enantiomer. Binding close to
the chiral centre may cause the same type of activity but of a different magnitude. A different pharmacological
activity for each enantiomer almost certainly reflects different receptors.
Further, drug absorption, distribution, and elimination from the body may vary due to differences in protein
binding, enzymic modification, etc, since proteins are also chiral entities (see Chapter 13).
Thus, the anticholinergic activity of the alkaloid
hyoscyamine
is almost entirely confined to the (
−
)-isomer, and
the (
+
)-isomer is almost devoid of activity. The racemic (
±
)-form, atropine, has approximately half the activity
of the laevorotatory enantiomer. An anticholinergic drug blocks the action of the neurotransmitter acetylcholine,
and thus occupies the same binding site as acetylcholine. The major interaction with the receptor involves that
part of the molecule that mimics acetylcholine, namely the appropriately positioned ester and amine groups. The
chiral centre is adjacent to the ester, and also influences binding to the receptor.
the descriptors
R
,
S
, and
RS
are defined in Section 3.4.2
N
N
N
Me
Me
Me
CH
2
OH
H
CH
2
OH
H
CH
2
OH
O
O
O
R
RS
S
O
O
O
(±)-hyoscyamine (atropine)
(+)-hyoscyamine
(-)-hyoscyamine
relative
anticholinergic
activity (%)
0
50
100
The major constituent of caraway oil is (
+
)-
carvone
, and the typical caraway odour is mainly due to this
component. On the other hand, the typical minty smell of spearmint oil is due to its major component, (
−
)-
carvone. These enantiomers are unusual in having quite different smells, i.e. they interact with nasal receptors
quite differently. The two enantiomeric forms are shown here in their half-chair conformations.
H
O
O
O
O
H
half-chair conformation;
isopropenyl group
nearly equatorial
half-chair conformation;
isopropenyl group
nearly equatorial
(+)-carvone (caraway)
(-)-carvone (spearmint)
