Synthetic approaches toward small molecule libraries

Abstract The drug discovery process is long and arduous, as it is estimated that the chance for a new molecule to reach the market as a rug is only 1:10,000. Thus, there is a need of a high number of small molecules, which differ not only for the appendages, but also for the molecular skeleton, to increase the chance of finding new lead compounds. From the birth of medicinal chemistry as a scientific discipline in 1930 to our days, organic chemists have developed a large variety of different synthetic methods to improve the quality and quantity of small molecules representing a library. In this chapter, the main methods are described, spanning through solid-phase techniques, combinatorial chemistry, diversity-oriented synthesis, and biology-oriented synthesis, with an emphasis on historical perspective and comparative evaluations.