Combinatorial chemistry strategies

Several examples have appeared in the literature in which this linker has been employed in combinatorial chemistry strategies. Thus, it has been used in a Pd-mediated three-component coupling strategy for the solid-phase synthesis of tropane derivatives [46], in the solid-phase synthesis of aspartic acid protease inhibitors [47], in the attachment of cholic acid as a template for a combinatorial approach [48] and, more recently, in the solid-phase synthesis of pyrrolidines via 2-aza allyl anion cycloadditions with alkenes [49]. 

Palma MS, Nakajima T (2005) A natural combinatorial chemistry strategy in acylpolyamine toxins from nephUinae orb-web spiders. Toxin Rev 24 209-234... 

F. Guillier, D. Grain and M. Bradley, Linkers and Cleavage Strategies in Solid-phase Organic Synthesis and Combinatorial Chemistry, Chem Rev 100 2091-2157 2000. 

Although the reciprocal approach potentially enables the screening of large numbers of compounds, only the advent of combinatorial chemistry brought about the tools required for the synthesis of large libraries of potential selectors in a very short period of time. In addition, using the methods of combinatorial chemistry, novel strategies different from those of the reciprocal approach could also be developed. 

The feasibility of multistep natural product total synthesis via solid-phase methodology, and its application to combinatorial chemistry, was first demonstrated by Nicolaou and coworkers in epothilone synthesis and in the generation of an epothilone library [152]. The traceless release of TBS-protected epoC 361 by RCM of resin-bound precursor 360 (Scheme 69) is an early and most prominent example for the strategy outlined in Fig. 11a. 

Due to the rising interest in supramolecular structures and nanoarchitectures, as well as their broad applicability, including the field of combinatorial chemistry, iterative strategies will gain more and more importance in preparative organic chemistry [60]. 

In addition, SPOS can easily be automated using appropriate robotics for both filtration and evaporation of the volatiles from the reaction mixture to obtain the cleaved product. Furthermore, SPOS can be applied to the powerful split-and-mix strategy, which has proved to be an important tool in combinatorial chemistry [7]. 

Combinatorial chemistry has been used with great success to create libraries in the development of inhibitors in the field of peptide and nucleic acid recognition.5,6 The basic strategy of a library approach is to synthesize large sets of molecules at a time, even as complex mixtures, and then determine whether any of the compounds is inhibitory. The active compound must be subsequently identified. This strategy stands in contrast to the extremely laborious and expensive process of traditional medicinal chemistry, where individual molecules are carefully synthesized and evaluated. The... 

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