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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 model 7. 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 model 10. 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!