Chapter 29 Optical Isomerism, Chirality, Drug Synthesis

Question 1

Chiral carbon / centre

Answer 1

A carbon atom that has 4 different atoms or groups of atoms attached to it.

Question 2

Enantiomer. (4)

Answer 2

• optical isomer
• identical physical & chemical properties
• differ in their ability to rotate plane polarised light (1 optical isomer rotates the plane of polarised light in the clockwise direction, the other optical isomer will rotate it in the anti-clockwise direction)
• have different biological activity

Question 3

Explain the biological activity of enantiomers. (4)

Answer 3

• Enantiomers differ from each other in terms of biological activity.
• Enzymes are chiral proteins that speed up chemical reactions by binding substrates.
• They have a specific binding site / active site & will only bind molecules that have the exact same shape.
• Therefore, if one enantiomer binds to a chiral enzyme, the mirror image of this enantiomer will not bind nearly as well if at all.

Question 4

Explain the term “optically active”.

Answer 4

• When a solution has an uneven mixture of each enantiomer.
• Rotates plane polarised light clockwise or anticlockwise

Question 5

Racemic mixture. (2)

Answer 5

• Equal amounts of enantiomers present in the solution.
• Optically inactive as enantiomers cancel out each others’ effect & the plane of polarised light will not change.

Question 6

Enantiomer that rotates the plane clockwise

Answer 6

R enantiomer (optically active)

Question 7

Enantiomer that rotates the plane anticlockwise

Answer 7

S enantiomer (optically active)

Question 8

Effect of optical isomers on plane polarised light. (3)

Answer 8

• When a beam of plane polarized light passes through a solution of certain organic molecules / racemic mixture / optical isomers, the plane of polarization is rotated through an angle, α.
• When a solution of known concentration of an optically active material is placed in the polarimeter, the beam of light is rotated either to the right (clockwise) or to the left (anti-clockwise).
• No effect observed when the sample is a racemic mixture.

Question 9

9701/42/M/J/23:
Suggest benefits & disadvantages of producing a drug such as perindopril as a single pure optical isomer.

Answer 9

Benefits:
- less side effects
- higher biological efficiency / activity
- smaller dose required (as drug more potent)

Disadvantages:
- need to separate (a racemic mixture into a single stereoisomer)
- lower yield
- need a chiral catalyst (for synthesis so, expensive)

Question 10

Explain the relevance of chirality to the synthetic preparation of drug molecules including, the potential different biological activity of the 2 enantiomers.

Answer 10

• Most of the drugs that are used to treat diseases contain 1 or more chiral centres. This affects their potential biological activity & effectiveness as medicines.
• Drug compounds should be prepared by asymmetric synthesis / a process that produces just 1 isomer in order to increase the drugs’ effectiveness.
• Some drug enantiomers can have very harmful side effects.
• If conventional organic reactions are used, a racemic mixture is obtained.

Question 11

Explain the relevance of chirality to the synthetic preparation of drug molecules including, the need to separate a racemic mixture into 2 pure enantiomers.

Answer 11

• 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.
• Decreases patient’s dosage by half as the pure enantiomer is more potent & therefore reduces production costs.

Question 12

How to prepare pure enantiomers?

Answer 12

• Use optically active starting materials
• Chiral / optical, resolution
• Chiral catalyst (enzymes)

Question 13

How is optical resolution used to produce a pure enantiomer?

Answer 13

• Use a pure enantiomer of another optically active compound (chiral auxiliary) that will react with one of the isomers in the mixture.
• The new product formed will have different properties.
• The new product is converted back to the desired enantiomer in a simple reaction.
• Crystallisation is repeated to ensure purity.

Question 14

Disadvantages of optical resolution to produce a pure enantiomer?

Answer 14

• time-consuming
• uses extra reagents
• disposes of half the original racemic mixture

Question 15

What type of chromatography is used to separate a racemic mixture? (2)

Answer 15

• HPLC
• Stationary phase must be a chiral auxiliary

Question 16

Advantages of using chiral catalysts to produce pure enantiomers? (2)

Answer 16

• only small amounts needed
• can be reused

Question 17

How to use optically active starting materials to produce pure enantiomers?

Answer 17

• Starting materials are optically active & in the same orientation as the desired product.
• This synthetic route is designed to keep any intermediates & the final product formed in the same enantiomeric form.

Question 18

Advantage of using optically active starting material to produce pure enantiomers?

Answer 18

• no need to carry out costly separation process needed when a racemic mixture is produced

Question 19

How do enzymes work as biological chiral catalysts to produce pure enantiomers? (3)

Answer 19

• Promote stereoselectivity (preference of a reaction to form 1 enantiomer over the other)
• Due to the specific binding site of enzymes, only 1 enantiomer is formed.
• 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.

Question 20

Advantage & disadvantage of using enzymes to synthesise drugs.

Answer 20

Advantage:
- Greener process as fewer steps involved compared to conventional synthetic routes

Disadvantage:
- Expensive to isolate them from living organisms (Thus, more research has recently been carried out into designing synthetic enzymes.)

Question 21

FAQ: A drug has 2 isomers. Why might the drug manufacturer try to produce a medicine consisting of only 1 of the 2 isomers? (3)

Answer 21

• Economically more sensible - no material wastage if one of the isomers is useful
• Even if one of the isomers is inactive, it might still have unexpected side-effects
• Give less drug to a patient (if you only give them the active isomer)

Question 22

FAQ: Many naturally occurring materials have some medicinal properties. Suggest a possible advantage of manufacturing synthetic equivalents of these materials rather than extracting them from natural sources.

Answer 22

• Expensive or **Time-consuming to extract enough of a drug from a natural source
• Possible to design a better drug than the one from the natural source by changing the molecule to make it safer / more effective

Question 23

FAQ: Explain why computer modelling has helped in the design of modern drugs. (3)

Answer 23

• Make 3D computer models of potential drugs & the active site it has to attach to
• Can quickly identify whether the molecule is specific to the active site
• Saves time (no need for random testing)

Question 24

FAQ: Even after designing a drug using computer modelling, explain why it is still important to do thorough practical testing of the drug. (1)

Answer 24

• Might have side effects due to the drug reacting unexpectedly with other biological molecules