Transcript Optical Isomerism

Optical Isomerism
 Optical isomerism arises in organic
molecules that contain a carbon
atom attached to 4 different
atoms or groups.
 A carbon with 4 different atoms
or groups attached is called a
chiral centre.
 If a molecule has a chiral centre in
its structure, two mirror image
arrangements are possible in space.
They are non-superimposable
mirror images of each other: they
are optical isomers.
Chiral Carbon attached to 4
different atoms or groups.
 Optical isomers rotate plane polarised light in opposite directions:
one rotates light clockwise and the other anticlockwise.
 A mixture containing equal amounts of each isomer is known as a racemic
mixture. A racemic mixture has no effect on plane polarised light
because the rotations cancel each other out.
Chirality in Pharmaceutical Synthesis
Why is chirality in drug synthesis important?
The drug Thalidomide was prescribed during the 50s and 60s to
prevent morning sickness in pregnant women. The drug was a
chiral compound:
 One of the stereoisomers has the desired therapeutic effect
 The other stereoisomer led to deformities in developing
babies.
Biological molecules have
complex three
dimensional structures
that bind to a drug
molecule in only one
possible way. The 3D
structure of a drug
determines its
pharmacological activity
and whether it will have
the desired therapeutic
effect or not.
The production of a single isomer with the
correct pharmacological activity presents 2 main
advantages to pharmaceutical companies.:
1. Risks from undesirable side effects are
reduced: if thalidomide has been used as the
‘correct’ single optical isomer, morning sickness
would have been prevented without the
deformities caused by the other optical isomer.
2. Drug doses are reduced: often when racemic
mixtures are given as drugs, half of the dosage
is wasted because only 1 of the isomers has the
desired therapeutic effect. Making a drug
containing only the one optical isomer should
reduce the desired dose by half.
Chirality in Pharmaceutical Synthesis
When a chiral compound is
synthesised in the lab, a mixture of
optical isomers is usually formed.
When the same material is made
naturally in a living system,
it is produced as a
single optical isomer.
After preparing a chiral compound in the
lab, complicated separation techniques are
required to isolate the pharmacologically
active isomer. Separation is difficult
because optical isomers tend to have the
same physical properties – melting points,
boiling points and solubilities. Separation
techniques often include the use of
enzymes, electrophoresis and
chromatography. This takes lots of time and
is expensive.
Modern Chiral Synthesis: there are a number of methods being used or
developed to prepare single chiral isomers:
 Using enzymes as biological catalysts: nature is good at making single
optical isomers
 Chiral Pool Synthesis: this uses naturally occurring chiral molecules
within the synthetic route such as α-amino acids and sugars.
 Using transition element complexes to produce chiral catalysts
which could transfer their chirality to produce a single isomer
product.