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 isomer 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 that 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 a 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
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
