Improved Methodology for the Preparation of Chiral Amines

O
O
O
*
NH
Thalidomide
(R)-active agent
(S)-teratogenic
O
*
H
N
OH
Ethambutol
(R,R)-blinding agent
(S,S)-tuberculostatic
2
Limonene
(S)-lemon odor
Limonen
(R)-organge odor
O
Carvone
(S)-caraway
O
Carvone
(R)-spearmint
H 2 N
OH 2 N
H
O
Asparagine
(S)-bitter
OH
HO
O
H
NH 2 O
Asparagine
(R)-sweet
NH 2
HO
H
O
O
H
N
NH
H 2
O
O
O
O
H
O
O
N
H
H 2 N
H
OH
Aspartame
(S,S)-sweet
Aspartame
(R,R)-bitter
Figure 1.1 Absolute Configuration vs Biological Activity.
Another example showing the importance of distinguishing the two enantiomers is the
distinguished effect of different isomeric forms of the nonsteroidal anti inflammatory drugs
(NSAIDs). They include ibuprofen (Advil), naproxen (Aleve), ketoprofen (Oruvail), and
flurbiprofen (Ansaid), which have found widespread use as pain relievers. The antiinflammatory
activity of these profens resides primarily with the (S)-enantiomer. The
enantiomers of flurbiprofen possess different pharmacokinetic properties and show
substantial racemization under physiological conditions. Although (S)-naproxen is the only
profen that was originally marketed in enantiopure form, in vivo interconversion of the
enantiomers of NSAIDs is an important issue in preclinical pharmacological and
toxicological studies. [16]
Also beta-blokers, the most widely used pharmaceutical agents for angina, hypertension, and
arrhythmias. It is known that for most beta-blockers the (S)-enantiomer is the most active
enantiomer. The S-enantiomer has the same three dimensional structure as the adrenergic
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