Chemistry Reference
In-Depth Information
Molecules with more than one chiral centre
Since there are two possible configurations for an asymmetrically substi-
tuted carbon atom, a structure containing
n
such centres will, in theory,
possess 2
n
stereoisomers. The actual number of stereoisomers that exist
may be less than this due to steric effects. Compounds that have the same
stereochemistry at one chiral centre but different stereochemistry at the
others are known as
diastereoisomers
(diastereomers); a good example is
given by the alkaloids ephedrine and pseudoephedrine. Ephedrine (the (1
R
,
2
S
) diastereoisomer) is a natural product isolated from Ephedra (the
Ma
Huang
plant) and known to Chinese medicine for over 3000 years. It was
used in the last century for the treatment of asthma. Pseudoephedrine (the
(1
S
, 2
S
) diastereoisomer) is a decongestant and a constituent of several
'over-the-counter' cold and flu remedies (Figure 4.12).
OH
H
OH
H
CH
3
CH
3
NHCH
3
NHCH
3
H
H
Ephedrine
Pseudoephedrine
Figure 4.12
The structures of ephedrine and pseudoephedrine.
Diastereoisomers (unlike enantiomers) have different physical proper-
ties such as boiling point, density, etc. These differences between
diastereoisomers can be exploited to resolve (or separate) mixtures of enan-
tiomers. The principle behind this technique is to resolve the mixture of
enantiomers by chemically converting them into a pair of diastereoisomers.
This is achieved by reacting the racemic mixture with an optically pure
reagent. These reagents are usually natural products; for example, if the
racemic mixture contains acidic compounds, reaction is with an optically
pure alkaloid such as strychnine or brucine.
Similarly, if the racemic mixture is composed of basic drugs, use is
made of camphor-10-sulfonic acid, a natural product obtainable as an
optically pure enantiomer. An example of the type of reactions involved is
shown in Figure 4.13, where a pair of enantiomeric alcohols is resolved by
reaction with phthalic anhydride and an optically pure base to form a pair
of diastereoisomeric salts. Reactions of this type can be tedious to perform
and, with the advent of HPLC with chiral stationary phases, are gradually
being replaced.
