CONFIGURATIONAL ISOMERS
85
O
NMe 2
clomifene
priority 1
priority 2
priority 1
priority 2
configuration (Z)
Cl
As can be deduced from application of the
Cahn–Ingold–Prelog priority rules, high-priority
groups are positioned on the same side of the double
bond in each case. Note that the substituted aromatic
ring has higher priority than the unsubstituted ring.
Both tamoxifen and clomifene thus have the Z configuration.
N
H
N
Me
triprolidine
priority 1
priority 2
priority 1
priority 2
configuration (E)
The antihistamine drug triprolidine has the E
configuration; note that the heterocyclic pyridine ring
takes priority over the benzene ring, even though
the latter has a substituent. Priority is deduced by
working along the carbon chain towards the first atom
that provides a decision, in this case the nitrogen
atom in the pyridine.
3.4.4 Configurational isomers with several
chiral centres
Configurational isomerism involving one chiral centre
provides two different structures, the two enantiomers.
If a structure has more than one chiral centre, then there
exist two ways of arranging the groups around each
chiral centre. Thus, with n chiral centres in a molecule,
there will be a maximum number of 2
n configurational
isomers. Sometimes, as we shall see in Section 3.4.5,
there are less.
Starting with two chiral centres, there should, therefore, be four stereoisomers, and this is nicely exemplified by the natural alkaloid (−)-ephedrine, which is
employed as a bronchodilator drug and decongestant.
Ephedrine is (1R,2S)-2-methylamino-1-phenylpropan1-ol, so has the structure and stereochemistry shown.
CH 3
Ph
H
HO
NHCH 3
H
H 3 C
Ph
H
OH
H 3 CHN
H
CH 3
Ph
H
H
NHCH 3
HO
H 3 C
Ph
H
H
H 3 CHN
OH
1 2
1S,2S
(+)-pseudoephedrine
1
2
1
1R,2S
(–)-ephedrine
1
2
1R,2R
(–)-pseudoephedrine
1S,2R
(+)-ephedrine
mirror
1S,2S
(+)-pseudoephedrine
1R,2S
(–)-ephedrine
1R,2R
(–)-pseudoephedrine
1S,2R
(+)-ephedrine
enantiomers
diastereoisomers
enantiomers
diastereoisomers
diastereoisomers
2
Now the other three of the possible four stereoisomers
are the (1S,2S), (1R,2R), and (1S,2R) versions. These
are also shown, and mirror image relationships are
emphasized. The (1S,2R) isomer is the mirror image
of (−)-ephedrine, which has the (1R,2S) configuration.
Therefore, it is the enantiomer of (−)-ephedrine, and can
be designated (+)-ephedrine. Note that the enantiomeric
form has the opposite configuration at both chiral
centres.
The other two isomers are the (1S,2S) and (1R,2R)
isomers, and these two also share a mirror image relationship, have the opposite configuration at both chiral centres, and are, therefore, a pair of enantiomers.
From a structure with two chiral centres, we thus have
four stereoisomers that consist of two pairs of enantiomers. Stereoisomers that are not enantiomers we term
diastereoisomers, or sometimes diastereomers. Thus,
the (1S,2S) and (1R,2R) isomers are diastereoisomers
of the (1R,2S) isomer. Other enantiomeric or diastereomeric relationships between the various isomers are
indicated in the figure.
85
O
NMe 2
clomifene
priority 1
priority 2
priority 1
priority 2
configuration (Z)
Cl
As can be deduced from application of the
Cahn–Ingold–Prelog priority rules, high-priority
groups are positioned on the same side of the double
bond in each case. Note that the substituted aromatic
ring has higher priority than the unsubstituted ring.
Both tamoxifen and clomifene thus have the Z configuration.
N
H
N
Me
triprolidine
priority 1
priority 2
priority 1
priority 2
configuration (E)
The antihistamine drug triprolidine has the E
configuration; note that the heterocyclic pyridine ring
takes priority over the benzene ring, even though
the latter has a substituent. Priority is deduced by
working along the carbon chain towards the first atom
that provides a decision, in this case the nitrogen
atom in the pyridine.
3.4.4 Configurational isomers with several
chiral centres
Configurational isomerism involving one chiral centre
provides two different structures, the two enantiomers.
If a structure has more than one chiral centre, then there
exist two ways of arranging the groups around each
chiral centre. Thus, with n chiral centres in a molecule,
there will be a maximum number of 2
n configurational
isomers. Sometimes, as we shall see in Section 3.4.5,
there are less.
Starting with two chiral centres, there should, therefore, be four stereoisomers, and this is nicely exemplified by the natural alkaloid (−)-ephedrine, which is
employed as a bronchodilator drug and decongestant.
Ephedrine is (1R,2S)-2-methylamino-1-phenylpropan1-ol, so has the structure and stereochemistry shown.
CH 3
Ph
H
HO
NHCH 3
H
H 3 C
Ph
H
OH
H 3 CHN
H
CH 3
Ph
H
H
NHCH 3
HO
H 3 C
Ph
H
H
H 3 CHN
OH
1 2
1S,2S
(+)-pseudoephedrine
1
2
1
1R,2S
(–)-ephedrine
1
2
1R,2R
(–)-pseudoephedrine
1S,2R
(+)-ephedrine
mirror
1S,2S
(+)-pseudoephedrine
1R,2S
(–)-ephedrine
1R,2R
(–)-pseudoephedrine
1S,2R
(+)-ephedrine
enantiomers
diastereoisomers
enantiomers
diastereoisomers
diastereoisomers
2
Now the other three of the possible four stereoisomers
are the (1S,2S), (1R,2R), and (1S,2R) versions. These
are also shown, and mirror image relationships are
emphasized. The (1S,2R) isomer is the mirror image
of (−)-ephedrine, which has the (1R,2S) configuration.
Therefore, it is the enantiomer of (−)-ephedrine, and can
be designated (+)-ephedrine. Note that the enantiomeric
form has the opposite configuration at both chiral
centres.
The other two isomers are the (1S,2S) and (1R,2R)
isomers, and these two also share a mirror image relationship, have the opposite configuration at both chiral centres, and are, therefore, a pair of enantiomers.
From a structure with two chiral centres, we thus have
four stereoisomers that consist of two pairs of enantiomers. Stereoisomers that are not enantiomers we term
diastereoisomers, or sometimes diastereomers. Thus,
the (1S,2S) and (1R,2R) isomers are diastereoisomers
of the (1R,2S) isomer. Other enantiomeric or diastereomeric relationships between the various isomers are
indicated in the figure.