Green Chemistry

The way chemists choose to make chemicals has a big impact on the quantity of waste, energy use, and time needed to complete the reaction. In pharmaceutical chemistry, the molecules are usually complex and require several reactions, one after the other to reach the final product. The molecular complexity of most active pharmaceutical ingredients means there are dozens of feasible ways to make them. If you look at the molecular structures of the top 200 drugs, you will see specific arrangements of atoms, often based on nitrogen (N), oxygen (O), or fluorine (F) attached to a carbon framework. The type, number, and orientation of these 'functional groups' determines the function and activity of the molecule in the body. The chemists needs to decide on the reactants to install each functional group, and in which order to do so. Much of the art of synthetic chemistry comes down to the design of a successful reaction sequence. In many cases, there is no obvious way all the functional groups can be created without issues. Some functional groups will interfere with certain chemistries, stopping the reaction, or they may degrade under harsh conditions (e.g. heating). The way chemists combat this is by modifying functional groups to be more stable or otherwise unreactive. A extra reaction is needed to install the so-called 'protecting group'. Once the next set of chemical reactions have been completed, a deprotection is performed, which is a reaction to remove the protecting group. As you can see, each protecting strategy introduces 2 more reactions, which is why this principle of Green Chemistry advises against them.

There are a variety of elegant ways protecting groups can be avoided, and more generally ways the number of reactions can be reduced:

• Design the synthesis to install the most sensitive functional group(s) last.

• Perform multi-component synthesis, where 3 or more reactants are combined at the same time. If performed right, the correct chemical bonds will form and the functional groups created together.

• Use techniques that work under mild conditions, preventing the thermal decomposition of delicate functional groups and avoiding highly reactive (and less selective) reagents. Biocatalytic enzymes are one example.

• Occasionally, new chemistry is invented to do specific reactions without destroying other functional groups.