ABSTRACT
Combinatorial chemistry is the chemistry characterized by divergent synthesis, which makes possible the synthesis of larger numbers of samples than by linear or convergent synthesis. At its heart is an acceptance of the precept that our ability to predict some useful properties of molecules based on their structures is yet immature. Nevertheless, the discovery of molecules with useful properties can yield enormous value. It follows that the search for properties benefits by having access to many samples with different structures. This is the paradigm used by nature in situations where survival is the motivating force. Thus, one focus of combinatorial chemistry is the synthesis of large numbers (i.e., thousands and up) of compounds in amounts sufficient to test. This approach to lead generation has been addressed using the split-mix approach described by Furka and adapted to small organic molecules by Pharmacopeia (see Chapter 7 in this Section) and others.
