Improved Methodology for the Preparation of Chiral Amines

molecule recognizes one of two enantiomeric guest molecules. There are numerous examples
of enantiomeric effects which are frequently dramatic. Thus, the enantiomers of limonene,
both are found in nature, smell differently, because our nasal receptors are made of chiral
molecules that interact with these enantiomers differently. Similarly one enantiomer of the
amino acid asparagine tastes sweet while the other tastes bitter. Clearly living systems are
very sensitive to chirality and many pharmaceutical drugs consist of chiral moieties. Chiral
drugs are a subgroup of drug substances that contain one or more chiral centres. It is well
established that the opposite enantiomer of a chiral drug often differs significantly in its
pharmacological, [12] toxicological, [13] pharmacodynamic and pharmacokinetic properties. [14]
A renowned example of how chirality affects the pharmacological action of the drugs, a
chiral drug is thalidomide (Thalidomid, Contergan) which was prescribed to pregnant women
in the 1960s to alleviate morning sickness. One of the enantiomeric forms of thalidomide
does indeed have sedative and antinausea effects, but the other enantiomer is a potent
teratogen. The racemic drug was approved in Europe for the treatment of pregnant women
suffering from nausea and its use caused severe birth defects. Even formulation of the pure
nontoxic (R)-enantiomer of thalidomide would have been unsafe because racemization takes
place in vivo and the teratogenic (S)-enantiomer is rapidly generated in the human body.
Since the thalidomide tragedy, the significance of the stereochemical integrity of biologically
active compounds has received increasing attention and the investigation of the
stereodynamic properties of chiral molecules has become an integral part of modern drug
development. [15]
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