Chirality & Drug Production (Cambridge (CIE) A Level Chemistry)

Chirality & Drug Production

• Most of the drugs that are used to treat diseases contain one or more chiral centres

• These drugs can therefore exist as enantiomers which differ from each other in their ability to rotate plane polarised light

• Another crucial difference between the enantiomers is in their potential biological activity and therefore their effectiveness as medicines

• Drug compounds should be prepared in such a way that only one of the optical isomers is produced, in order to increase the drugs’ effectiveness

  • Some drug enantiomers can have very harmful side effects

Potential biological activity of enantiomers

• If conventional organic reactions are used to make the desired drug, a racemic mixture will be obtained

  • In a racemic mixture, there are equal amounts of the two enantiomers

• The physical and chemical properties of the enantiomers are the same, however, they may have opposite biological activities

• For example, the drug naproxen is used to treat pain in patients who suffer from arthritis

  • One of the enantiomers of naproxen eases the pain, whereas another enantiomer causes liver damage

• One enantiomer of a drug used to treat tuberculosis is effective whereas another enantiomer of this drug can cause blindness

• Thalidomide is another example of a drug that used to be used to treat morning sickness, where one of the enantiomers caused very harmful side effects for the unborn baby

Separating racemic mixtures

• Due to the different biological activities of enantiomers, it is very important to separate a racemic mixture into pure single enantiomers which are put in the drug product

• This results in reduced side-effects in patients

  • As a result, it protects pharmaceutical companies from legal actions if the side effects are too serious

• It also decreases the patient’s dosage by half as the pure enantiomer is more potent and therefore reduces production costs

  • A more potent drug has better therapeutic activity

Chiral catalysts

• In order to produce single, pure optical isomers, chiral catalysts can be used

• The benefits of using chiral catalysts are that only small amounts of them are needed and they can be reused

  • For example, an organometallic ruthenium catalyst is used in the production of naproxen which is used in the treatment of arthritis

Using catalysts to direct the production on one enantiomer

The organometallic ruthenium catalyst is a chiral catalyst which ensures that only one of the enantiomers is formed which can be used in treating arthritis

• Enzymes are excellent biological chiral catalysts that promote stereoselectivity and produce single-enantiomer products only

  • Stereoselectivity refers to the preference of a reaction to form one enantiomer over the other

• Due to the specific binding site of enzymes, only one enantiomer is formed in the reaction

• The enzymes are fixed in place on inert supports so that the reactants can pass over them without having to later separate the product from the enzymes

• The disadvantage of using enzymes is that it can be expensive to isolate them from living organism

  • Therefore, more research has recently been carried out into designing synthetic enzymes

• Although using enzymes to produce pure enantiomers in drug synthesis takes longer than conventional synthetic routes, there are many advantages to it in the long run

  • For example, using enzymes to synthesise drugs is a greener process as fewer steps are involved compared to conventional synthetic routes