Branching cascades strategy

Scaffold Diversity Synthesis with Branching Cascades Strategy... 

Chemical/Biological Evaluation - Branching Cascades Strategy in Scaffold Diversity Synthesis 399... 

Figure 27.4 Nucleophiles used in reaction screening in branching cascade strategy.

Mechanistic insights as proposed by Kumar and coworkers supported the very design of the branching cascade strategy because the successful nucleophiles have utilized the dispersed electrophilic sites over the surface of common precursors 27 beautifully to provide different products via different cascade reactions (Scheme 27.4). In many cases, the reaction sequence apparently begins with the addition of nucleophiles to aldehyde or ketoester moiety and followed by further cyclization on to the chromones moiety (cascades I, III, IV, VI) before the second nucleophilic addition or rearrangement leading to diverse 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... 

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