chirality

Question 1

Explain why only 25% of the dose was effective. Suggest how the synthesis of compound D might be changed to make the dose more effective.

Answer 1

(compound D has) two chiral centres 
Four optical isomers exist 
(Synthesis could) use enzymes OR bacteria
OR use (chemical) chiral synthesis OR chiral catalysts
OR use natural chiral molecules OR single isomers (as
starting materials)

Question 2

Suggest two benefits of using single stereoisomers in the synthesis of drugs such as enalapril.

Answer 2

any two from:
no/fewer side effects
increases the (pharmacological) activity/effectiveness
Reduces/stops the need for/cost/difficulty in separating
stereoisomers/optical isomers

Question 3

Why does glycine not show optical isomerism?

Answer 3

There is no chiral carbon

OR there is no asymmetry in the molecule 

Question 4

α-Amino acids are being used in the development of peptide-based pharmaceuticals.
Optical isomerism has been found to be significant in the action of some pharmaceuticals.
• State two possible disadvantages of synthesising a peptide-based pharmaceutical that contains a mixture of optical isomers.
• State two methods that are used by manufacturers to synthesise pharmaceuticals containing just the required optical isomer.

Answer 4

Disadvantages:
any two from:
• (one stereoisomer might have harmful/adverse) side
effects
• reduces the (pharmacological) activity/effectiveness 
• cost of separating stereoisomers
OR difficulty in separating stereoisomers 
Synthesis of a single optical isomer
any two from:
• using enzymes or bacteria 
• using (chemical) chiral synthesis
OR using chiral catalysts 
• using (natural) chiral molecules/compounds 
Quality of Written Communication
For full marks to be awarded for this question chiral OR enzyme
OR bacteria OR catalyst must be spelled correctly at least once
in the correct context

Question 5

Suggest possible problems of making a chiral drug such as salbutamol and describe two ways that the pharmaceutical industry might overcome these problem

Answer 5

Mark 1 – production of a single isomer is more expensive/difficult
OR separation of the single isomer is expensive/difficult

Mark 2 – one of the isomers is more (pharmacologically) active or one of
the isomers might have adverse/harmful/nasty side effects

Marks 3 and 4 – problems are overcome by using:
Enzymes/bacteria/biological catalyst
Chiral synthesis
Chiral catalyst or transition metal complex
Start with a natural chiral molecule or chiral pool