Organic Synthesis Strategies for Pharmaceuticals

1. Starter • Suggest a two-step synthesis for 3-aminopropanoic acid from 3-bromopropanol. • Suggest a two step synthesis for butanol acid from ethyl butanoate.

2. Organic Synthesis of aromatic compounds L.O.: Devise multi-stage synthetic routes for preparing aromatic organic compounds.

4. Structures of benzene and 3-chloronitrobenzene

5. Converting benzene into nitrobenzene

6. Chlorination of an aromatic ring

7. Task: Propose a retro-synthesis of paracetamol

8. Chirality in pharmaceutical synthesis • Explain that the synthesis of pharmaceuticals often requires the production of a single optical isomer. • Explain that synthetic molecules often contain a mixture of optical isomers, whereas natural molecules often have only one optical isomer. • Explain that the synthesis of a pharmaceutical that is a single optical isomer increases costs, reduces side effects and improves pharmacological activity. • Describe strategies for the synthesis of a pharmaceutical with a single optical isomer.

9. Very potent M3 antagonist. Clinical candidate for COPD Task: • Dr Bravo synthesised the above compound as a mixture of enantiomers. In pairs discuss the disadvantages of using the mixture of enantiomers as a clinical candidate for COPD. • In pairs discuss possible solutions to overcome the problems aforementioned.

10. Disadvantages: • One of the enantiomers may have a harmful effect • Larger dose needed. 2) • Purifying the mixture using chiral HPLC • Synthesise a single chiral isomer

11. Modern chiral synthesis How to prepare a single chiral isomer: • Using enzymes. • Chiral pool synthesis (starting from chiral molecules) • Use transition element complexes.

12. Stereoisomers of thalidomide

13. Pharmacological activity depends on whether or not a drug can interact with a receptor site in a biological system.

14. Structure of ibuprofen, used in many medicines to relieve pain