Reagent-based selection

In general, reagent-based selection is much faster and more convenient to execute in the laboratory as compared with the product-based selection. On the other hand, the latter strategy usually provides more accurate results. There exists a potential to combine both approaches to achieve more optimal results, particularly in the case of large exploratory virtual combinatorial libraries, for which mass random synthesis and screening are not economically feasible. In this article, we demonstrated the usefulness of property-based approach for selection of optimal GPCR ligands. 

PRODUCT-BASED SELECTION 1,000,000,000 generated and characterized structures REAGENT-BASED SELECTION 3500 characterized structures... 

Figure 5.10 Virtual libraries product-based and reagent-based selection methods.

There are two different approaches that can be taken to reagent selection. In reagent-based selection, each pool of reagents is handled independently. An alter-... 

Product-based selection is much more computationally demanding than reagent-based selection. Typically, it requires the computational enumeration of the full virtual combinatorial library and calculation of the descriptors for all possible products, prior to the application of a subset selection method. Consider a three-component reaction with 100 reagents available at each substituent position and assume that the aim is to build a 10 x 10 x 10 combinatorial library. In reagent-based selection, this requires the calculation of descriptors for 300 compounds (100 + 100 + 100). In product-based design, however, the full library of 1 million compounds (100 x 100 x 100) must be enumerated and descriptors must be calculated for each product molecule. 

Scheme 15.42 Reagent-based selectivity in the fluorination of imines.

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