Combinatorial catalysis library generation

By simulating evolution in vitro it has become possible to isolate artificial ribozymes from synthetic combinatorial RNA libraries [1, 2]. This approach has great potential for many reasons. First, this strategy enables generation of catalysts that accelerate a variety of chemical reactions, e.g. amide bond formation, N-glycosidic bond formation, or Michael reactions. This combinatorial approach is a powerful tool for catalysis research, because neither prior knowledge of structural prerequisites or reaction mechanisms nor laborious trial-and-error syntheses are necessary (also for non-enzymatic reactions, as discussed in Chapter 5.4). The iterative procedure of in-vitro selection enables handling of up to 1016 different compounds... 

The search for catalysts has many features in common with the search for biologically active compounds, most importantly pharmaceuticals In both cases, the aim is the discovery of a property, an effect. In classical pharmaceutical (or catalysis) research (Scheme 3, top), compound isolation and characterization precedes testing. As a consequence, a lot of effort may be invested on compounds that eventually do not show the desired properties (4,5). In the combinatorial approach, (Scheme 3, bottom) characterization comes after the discovery of a desired property, and it is limited to those compounds that show the desired property. As summarized in Scheme 3 (bottom), the key features of the combinatorial approach to catalyst discovery (and optimization) are (i) the generation of libraries of catalyst candidates, and (ii) the screening of the libraries for catalytic activity. Both aspects are dealt with in a general sense in Sections LB and I.C below. Section I.D summarizes the features specific for library generation and screening in the field of biomimetic oxidation catalysis. 

Using a split-and-pool combinatorial synthesis strategy, Tamanoi and coworkers developed a library of approximately 4000 heterocycles generated from resin-bound allenoates by means of phosphine catalysis [36,37]. This library was initially screened to identify GGTase I inhibitors (Table 8.1), and some potent GGTase I inhibitors with novel... 

B.xiv.c. Intermolecular Heck Reactions on Polymeric Support. Combinatorial chemistry has initiated a reappraisal and consequent renaissance in synthesis of compounds attached to polymeric supports. Therefore, it comes as no surprise that Pd-catalyzed reactions are among the most widely explored reactions for the generation of combinatorial libraries on solid phase. The first example of the intermolecular Heck reaction on solid phase was reported in 1994. In this article, 4-vinylbenzoic acid was attached to Wang resin and coupled with aryl halides/triflates under catalysis with Pd(OAc)2 (Scheme 45). Similar... 

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