Primary Libraries Shooting in the Dark

We call primary, or unbiased, or diversity based, the libraries that are not designed on the basis of structural information, but rather those intended as diverse collections of molecules as sources of active compKJunds for different targets. Examples of such hbraries have been reported frequentiy in the literature (1-3), and their main properties are shown in Fig. 5.1. 

Whenever a library is designed in a particular formaL some basic questions should be addressed to justify its synthesis. We will address them first in theory then we will apply the same principles to a published example of a primary library. 

The primary library shown in Fig. 5.2, which was reported by Baldwin (1), was clearly designed as a source of biologically active molecules on several targets (why), thus compensating the efforts required for the chemical assessment and for a satisfactory characterization (when). The SP library was prepared in pools using chemical encoding (4, 5) to produce a population of around 62,000 individuals (how). The synthetic scheme was composed of both simple and more complex SP steps, and several monomer sets (A-F, Fig. 5.2) were used (what). These monomers were either commercially available or easily prepared from commercial precursors, while the library benzopyranic core was formed during the synthesis (how much). 

After the design of a library in the most suitable format, the synthetic process starts with the chemical assessment. Usually the designed synthetic route is first tested in solution on one or a few representative structures, then its transfer onto SP is accomplished while optimizing the reaction conditions for model individuals. This process already has been described in detail in Chapter 3. 

A= first experimental conditions tried B= experimental condition adjustment S= successful F= failed 

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