What Is Not Combinatorial Chemistry

Although solid-phase synthesis is frequently linked to combinatorial chemistry, this is not a requirement. Other synthetic methodologies, such as solution-phase synthesis and soluble polymer-supported synthesis, have also been used to effect the combinatorial synthesis process. However, solid-phase synthesis allows the most efficient combinatorial synthesis. The advantages and problems with solid-supported synthesis are described in later chapters. Thus, combinatorial chemistry is not solid-phase chemistry, albeit combinatorial chemistry can be advantageously performed on the solid phase. 

Solid-phase combinatorial synthesis can be performed using the split-and-pool technique based on the combination of variously substituted compounds together for the same reaction in an appropriate reaction step, as well as by parallel synthesis, in which all compounds are segregated during all the reaction steps (see next chapters). Although parallel synthesis is an efficient way to prepare arrays of structurally unrelated compounds, it is not necessarily a combinatorial approach conventionally based on substituent modifications of one structural motif. Thus, combinatorial chemistry is not parallel synthesis, albeit combinatorial chemistry can be performed in parallel fashion. 

The obvious requirement for a synthesis to be regarded as combinatorial is that it is undertaken in a combinatorial manner, independent of the synthetic approach, size of a library, and degree of automation. 

PRACTICAL ASPECTS OF COMBINATORIAL SOLID-PHASE SYNTHESIS 

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