ABSTRACT
The synthesis of high quality combinatorial libraries depends on the development of optimal synthesis, analysis, and cleanup protocols. In our lead discovery library synthesis, we employ solid-phase and solution-phase parallel synthesis methods to produce libraries containing approximately 5000 compounds each (see Chapter 1). Our approach involves a series of feasibility and rehearsal procedures de signed to optimize the final production protocol. This is in contrast to the reaction optimization approach of process chemistry, which seeks the highest yield for a single reaction. The optimization in combinatorial chemistry seeks a set of reac tion conditions that provides an overall good yield for a diverse set of reactions. This set of reaction conditions may not be the best for every single reaction because it is unlikely that a single set of conditions exists that would give the highest yield and optimal kinetics for so many reactions. This complex process is referred to as chemistry optimization or validation. It is the most costly and time-consuming step, but it is the essential step in combinatorial or parallel syn thesis.
