Combinatorial chemistry

The basic principles

What is it about?

• Synthesising a large number of similar compounds in a short period of time.

• Compounds that are generated are analogues of compounds that are already biologically active

• Chemists want to find a new medicine that is more effective than an existing one, or causes fewer side effects

A simple model

1. Take some beads made from a polymer

2. React the beads with a group called a linker

3. Mix the bead in with an alcohol that you want to use in a chemical reaction. The linker will bind to it and hold it on the bead.

A simple model

4. Have 6 reaction vessels each containing a different acyl chloride. Put a 1/6 of your beads into a mesh bag and put into a container.

A simple model

5. Esterification occurs forming 6 different esters.

6. The beads are removed from the vessel by lifting up the mesh bag. They are washed to remove any unreacted acyl chloride

A simple model7. A reaction is used to break the linker

group down.

8. The polymer beads are reused

9. You have made 6 different esters which can now be tested for biological activity

A simple model10. How many esters would you have made

if you had attached 6 different alcohols to the beads?

A simple model

Large numbers of similar compounds have been synthesised in a very short period

of time. Imagine how much longer it would take if you did the reaction with one alcohol

and acyl chloride, and then did it again with a different acyl chloride, and then again,

and again…. 36 times!