Design combinatorial synthetic

The split-and-pool synthesis not only simplifies the complexity of the combinatorial synthetic process, but also offers additional important benefits. To undertake a full range of solid-phase chemical reactions, elaborate reaction conditions are needed for some chemical transformations. These include, but are not limited to, low temperature and inert atmosphere conditions. Parallel synthesis of a thousand compounds requires handling of a thousand reaction vessels. The timely addition of sensitive reagents (e.g., butyl lithium) at low temperature (—78°) under inert atmosphere during parallel synthesis is not a trivial task. It can be done if sophisticated automated synthesizer equipment is designed to handle and tolerate such reaction conditions. Such a synthesis can alternatively be performed easily in a manual fashion using a split-and-pool method that requires only a limited number of reaction vessels. Examples from Nicolaou s17 and Schrei-ber s18,19 laboratories have shown that the split-and-pool method is the methodology of choice for the synthesis of complex and diversity-oriented combinatorial libraries. 

Key Words Affinity biomimetic ligands synthetic proteins purification design combinatorial synthesis screening. 

Combinatorial Synthetic Design The Balance of Novelty and Familiarity... 

The use of seven-membered ring heterocycles in new medicinal agent design is likely to continue, especially in the context of the search for greater structural novelty from combinatorial synthetic methods. This promises to be a challenging area for the future. 

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