One enantiomeric form of a drug may be active, and the other may be
inactive, less active or even toxic. Not only drug molecules, but also various
other molecules that are essential for living organisms exist in stereoisomeric forms, and their biological properties are often specific to one
stereoisomer. Most of the molecules that make up living organisms are
chiral, i.e. show stereoisomerism. For example, all but one of the 20
essential amino acids are chiral. Thus, it is important to understand
stereochemistry for a better understanding of drug molecules, their action
and toxicity.
Ibuprofen is a popular analgesic and anti-inflammatory drug. There are
two stereoisomeric forms of ibuprofen. This drug can exist as (S)- and (R)stereoisomers (enantiomers). Only the (S)-form is active. The (R)-form is
completely inactive, although it is slowly converted in the body to the active
(S)-form. The drug marketed under the trade names, commercially known as
Advil
1 , Anadin
1 , Arthrofen
1 , Brufen
1 , Nurofen
1 , Nuprin
1 , Motrin
1
etc., is a racemic mixture of (R)- and (S)-ibuprofen.
H COOH
H COOH
(S)-Ibuprofen
Active stereoisomer
(R)-Ibuprofen
Inactive stereoisomer
*
*
In the early 1950s, Chemie Grunenthal, a German pharmaceutical company,
developed a drug called thalidomide. It was prescribed to prevent nausea or
morning sickness in pregnant women. The drug, however, caused severe
adverse effects on thousands of babies who were exposed to this drug while
their mothers were pregnant. The drug caused 12 000 babies to be born with
severe birth defects, including limb deformities such as missing or
stunted limbs. Later, it was found that thalidomide molecule can exist
in two stereoisomeric forms; one form is active as a sedative, but the
other is responsible for its teratogenic activity (the harmful effect on the
foetus).
N
O
O
N
O
O
H
H
N
O
O
N
O
O
H
H
Thalidomide stereoisomers
Sedative
Teratogenic
*
*
Limonene is a monoterpene that occurs in citrus fruits. Two enantiomers of
limonene produce two distinct flavours: (À)-limonene is responsible for the
flavour of lemons and (þ)-limonene for orange. Similarly, one enantiomeric
form of carvone is the cause of caraway flavour, while the other enantiomer
has the essence of spearmint.
54
CH3 STEREOCHEMISTRY
inactive, less active or even toxic. Not only drug molecules, but also various
other molecules that are essential for living organisms exist in stereoisomeric forms, and their biological properties are often specific to one
stereoisomer. Most of the molecules that make up living organisms are
chiral, i.e. show stereoisomerism. For example, all but one of the 20
essential amino acids are chiral. Thus, it is important to understand
stereochemistry for a better understanding of drug molecules, their action
and toxicity.
Ibuprofen is a popular analgesic and anti-inflammatory drug. There are
two stereoisomeric forms of ibuprofen. This drug can exist as (S)- and (R)stereoisomers (enantiomers). Only the (S)-form is active. The (R)-form is
completely inactive, although it is slowly converted in the body to the active
(S)-form. The drug marketed under the trade names, commercially known as
Advil
1 , Anadin
1 , Arthrofen
1 , Brufen
1 , Nurofen
1 , Nuprin
1 , Motrin
1
etc., is a racemic mixture of (R)- and (S)-ibuprofen.
H COOH
H COOH
(S)-Ibuprofen
Active stereoisomer
(R)-Ibuprofen
Inactive stereoisomer
*
*
In the early 1950s, Chemie Grunenthal, a German pharmaceutical company,
developed a drug called thalidomide. It was prescribed to prevent nausea or
morning sickness in pregnant women. The drug, however, caused severe
adverse effects on thousands of babies who were exposed to this drug while
their mothers were pregnant. The drug caused 12 000 babies to be born with
severe birth defects, including limb deformities such as missing or
stunted limbs. Later, it was found that thalidomide molecule can exist
in two stereoisomeric forms; one form is active as a sedative, but the
other is responsible for its teratogenic activity (the harmful effect on the
foetus).
N
O
O
N
O
O
H
H
N
O
O
N
O
O
H
H
Thalidomide stereoisomers
Sedative
Teratogenic
*
*
Limonene is a monoterpene that occurs in citrus fruits. Two enantiomers of
limonene produce two distinct flavours: (À)-limonene is responsible for the
flavour of lemons and (þ)-limonene for orange. Similarly, one enantiomeric
form of carvone is the cause of caraway flavour, while the other enantiomer
has the essence of spearmint.
54
CH3 STEREOCHEMISTRY