Synthetic Strategies for Exploring Biologically Relevant Chemical Space

2 Synthetic Strategies for Exploring Biologically Relevant Chemical Space 

A challenge in chemical biology is to design small molecule libraries that span large tracts of biologically relevant chemical space.The chemical space defined by small molecules is vast it has been estimated that there are 10 ° 

The diversity of chemical libraries may derive from the high substitutional, stereochemical and scaffold diversity of its members. Combinatorial chemistry is focused on the synthesis of chemical libraries with only high substitutional diversity. In general, combinatorial syntheses exploit a rather limited palette of chemical transformations to vary the substitution of library members. The synthesis of compound libraries with high substitutional diversity is described in Section 1.2.1. 

Varying the configuration of library members is more challenging, but has been hugely facilitated by the many reliable asymmetric transformations that have been developed in the past 30 years. In many cases, the high enantio-selectivity of these transformations can dominate over substrate-based dia-stereoselectivity, and allow the configuration of compounds to be varied systematically. The synthesis of a compound library with both high substitutional and stereochemical diversity is described in Section 1.2.2. 

---