Methods for the synthesis of macrocycle libraries for drug discovery

Macrocycles are found widely in nature where they fulfill numerous specific functions. However they have been generally underexploited as drug molecules, as they are larger than more conventional ‘Rule of 5’ compliant molecules and their synthesis and screening has been considered a challenge. Consequently most pharmaceutical companies have very few macrocycles in their screening files, and yet these compounds can have potent and selective pharmacological activity, and exhibit drug-like properties such as cell membrane permeability and oral bioavailability. To permit the further investigation of macrocyclic drugs, several groups have developed diverse methods for the rapid synthesis and screening of macrocyclic libraries.