Compound libraries scaffold diversity

Schreiber and co-workers have shown that this approach is useful in the preparation of compound libraries. One of their examples is a diversity-oriented synthesis of polycyclic scaffolds through the Perrier reaction followed by the PKR of a glycal template on solid support (Equation (35)). 

Viewing secondary metabolites from a chemical perspective, the scaffold diversity and polyfunctional features offer significant potential to generate random libraries for screening purposes. The structural status of a compound on this level is, therefore, a transition state with the goal to become a hit or a lead for further development (Table 7.2). Various automatic chromatographic separation techniques and modern spectroscopic methodologies can... 

Natural products are generally complex chemical structures, whether they are cyclic peptides like cyclosporin A, or complex diterpenes like paclitaxel. Inspection of the structures that are discussed in Section IV is usually enough to convince any skeptic that few of them would have been discovered without application of natural products chemistry. Recognition of this structural diversity has certainly made an impact on the design of combinatorial strategies, as exemplified by the 2 million plus compound library that was recently assembled by the Schreiber group using natural product-like structures as the initial scaffolds. 

Scaffold diversity is an important parameter to characterize any compound collection. Organic synthesis is expected to provide efficient approaches to create three-dimensionally complex and structurally diverse small molecules. Branching pathways in DOS is an elegant approach to access scaffold diversity that could lead to small, yet diverse, focused compound libraries. Branching cascades strategy has successfully demonstrated the power and application of cascade or domino reactions in compound collection synthesis to build rapidly complex scaffolds for library synthesis. Further synthesis endeavors toward branching pathways... 

In this chapter, we present an overview of domino reactions that have been used to construct various types of compound libraries targeting either natural product (NP) structures and privileged scaffolds or diverse ring systems. 

The diversity of chemical libraries may derive from the high substitutional, stereochemical and scaffold diversity of its members. Combinatorial chemistry is focused on the synthesis of chemical libraries with only high substitutional diversity. In general, combinatorial syntheses exploit a rather limited palette of chemical transformations to vary the substitution of library members. The synthesis of compound libraries with high substitutional diversity is described in Section 1.2.1. 

Synthesis of Compound Libraries with High Scaffold Diversity... 

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