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Optical Isomerism and Chirality in Pharmaceuticals
- #Stereoisomers: Species with the same structural formula
but with different arrangements of atoms on space
- Alkenes can show E/Z stereoisomerism provided each
carbon in the double bond is attached to two different groups
- #Optical Isomerism (enantiomers): Stereoisomers that
are non-superimposable mirror images of each other.
- To show optical isomerism, be optically active, the compound needs to
contain a chiral carbon this is attached to four different groups. Each chiral
carbon will form two optical isomers, mirror-image arrangements
- Optical isomers will rotate plane polarised light in different directions. A 50/50 mixture of two
optical isomers will have an equal effect on plane polarised light, this is called a racemic mixture.
- Example: Lactic acid in milk
and lactic acid in muscles
- Optical isomers will rotate plane polarised light in different directions. A 50/50 mixture of two
optical isomers will have an equal effect on plane polarised light, this is called a racemic mixture.
- #Chiral Carbon: A carbon atom attached to
four different atoms or groups of atoms
- Representing Optical Isomers: They must be drawn
showing the three dimensional arrangement around the
central carbon atom.
- e.g.
- e.g.
- -amino acids are optically active, apart from glycine, many sugars also display optical activity. In plants and
animals only one of the optical isomers is synthesised, and only one will interact with an enzyme due to the
stereospecific nature on enzyme. This is important as only one of the isomers may be biologically active.
- Chirality in Pharmaceutical Synthesis
- Examples: Thalidomide used to treat morning sickness, one isomer was pharmacologically beneficial the other caused deformities in babies.
Seldane used to treat symptoms associated with hay fever, one isomer reduced symptoms, the other caused a potentially fatal heart condition in
some patients
- #Pharmacological Activity: The beneficial or
adverse effects of a drug on living matter
- Drug licencing agencies have testing regimes to check the effect of each optical isomer. This is costly to drug
companies and so they have and so have researched the development and synthesis of just one optical isomer.
- Advantages:
- Risks from undesirable
side-effects are reduced
- Drug doses are reduced. When a drug containing a mixture of optical isomers is prescribed part of the
dose is wasted in the body because only one of the isomers has the desired effect therapeutic effect.
Therefore making a drug with only the beneficial isomer means the required does can be halved.
- Risks from undesirable
side-effects are reduced
- When a chiral compound is synthesised in the laboratory a mixture of optical
isomers is usually formed. But when the same material is made naturally in a
living system, it is produced as a single optical isomer. e.g. -amino acids in
nature
- In the laboratory separation of optical isomers is difficult as they usually have the same or very similar physical properties, melting and
boiling points and solubilities. Separation techniques include the use of enzymes, electrophoresis and chromatography. These take a
significant amount of time and are costly. Frequently th non-active isomer has to be disposed of if it cannot be sold on to other users.
- Advantages:
- Modern Chiral Synthesis: Preparing single chiral isomers
- Using enzymes as biological catalysts e.g. purified enzymes or enzyme containing microorganisms If
a synthetic route can be designed using enzymes than a single isomer can be produced
- Chiral pool synthesis. Makes use of naturally occurring chiral molecule, within the synthetic route.
The chirality of the original moecule can lead to the formation of a molecule that is a single pure
optical isomer. Common starting materials for this include natural -amino acids and sugars.
- Use of transition complexes as catalysts, they would transfer their
chirality to synthesise a single isomer product.
- Using enzymes as biological catalysts e.g. purified enzymes or enzyme containing microorganisms If
a synthetic route can be designed using enzymes than a single isomer can be produced
- Examples: Thalidomide used to treat morning sickness, one isomer was pharmacologically beneficial the other caused deformities in babies.
Seldane used to treat symptoms associated with hay fever, one isomer reduced symptoms, the other caused a potentially fatal heart condition in
some patients
- Chiral Drugs at Home: Ibuprophen
- Reduces bone and muscle pain by blocking pain messages to the
brain and reducing swelling/inflammation. Used for headaches,
back pain and arthritus
- It has one chiral carbon so two optical isomers are possible. One relieves pain more effectively than the other, the less
active form is converted into the more active form in the body, so the whole dose given to the patient is the more
pharmacologically active isomer; therefore it can be sold as a mixture of both isomers. Minimising possible side-effects.
- Reduces bone and muscle pain by blocking pain messages to the
brain and reducing swelling/inflammation. Used for headaches,
back pain and arthritus
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