Combinatorial selection, catalysts

On the other hand, most of the lyases allow a reasonably broad variation of the electrophilic acceptor component, which usually is an aldehyde. This feature, which nicely complements the emerging trend of combinatorial synthesis [38-40], makes possible a stereodivergent strategy for the synthesis of groups of stereoisomeric compounds by employing separate enzymatic catalysts to selectively produce individual diastereomers at will from the same starting material (Sect. 7). 

Combinatorial Selections of Catalysts from Nucleic Acid Libraries 381... 

For the combinatorial selection of RNA (or DNA)-transition-metal catalysts, further elements have to be developed and integrated into the scheme (Figure 18.3). In addition to a tethered substrate, a site-specifically attached transition metal ligand needs to be present in each molecule of the hbrary. After loading with the metal, it should allow formation of the catalytically active species, preferably with the reactant tethered to the same RNA molecule. The other reactant carries a purification tag, allowing the selective isolation of only those species in which a reaction had taken place. A further nontrivial requirement is that the attachment of the metal-hgand complex to DNA or RNA does not interfere with the enzymatic copying steps (transcription, reverse transcription (RT), polymerase chain reaction (PCR)). 

In this brief review we illustrated on selected examples how combinatorial computational chemistry based on first principles quantum theory has made tremendous impact on the development of a variety of new materials including catalysts, semiconductors, ceramics, polymers, functional materials, etc. Since the advent of modem computing resources, first principles calculations were employed to clarify the properties of homogeneous catalysts, bulk solids and surfaces, molecular, cluster or periodic models of active sites. Via dynamic mutual interplay between theory and advanced applications both areas profit and develop towards industrial innovations. Thus combinatorial chemistry and modem technology are inevitably intercoimected in the new era opened by entering 21 century and new millennium. 

The concept of minimum AE and maximum Emw is illustrated with the generalized sequence shown in Scheme 4.7 under stoichiometric conditions with complete recovery of reaction solvents, catalysts, and post-reaction materials. Markush structures are used to show both variable R groups and necessarily invariant atoms. This analysis is useful in studying combinatorial hbraries where a constant scaffold structure is selected and then is decorated with, in principle, an unlimited number of possible R groups. 

In the near future probably computer modelling, allowing the analysis of adsorption and elementary reactions at surfaces, will become increasingly helpful in catalyst selection. On the experimental side the field is changing drastically. Parallel testing equipment is now the state of the art. This field is often referred to as Combinatorial Chemistry . It is expected to have a large impact already in the near future. In fact, at present already companies have been formed in this field. 

The last few papers (38, 39, and 41) presented are examples where the ligands were not synthesized in a parallel or combinatorial fashion. However, by thinking about the optimization of reaction conditions in a parallel manner and by using ligands that are commercially available or easily synthesized, individual catalysts were found, which in some cases proceed with good selectivity. 

High selectivity and substrate specificity of glycosyl transferases make them valuable catalysts for special linkages in polymer-supported synthesis. There is, however, still a rather limited set of enzymes available to date, and the need to synthesize a variety of natural and non-natural oligosaccharides prevails. Particularly with regard to combinatorial approaches, chemical solid-phase oligosaccharide synthesis promises to meet the demands most effectively. 

Sharpless et al. coined the word ligand-accelerated catalysis (LAC), which means the construction of an active chiral catalyst from an achiral precatalyst via ligand exchange with a chiral ligand. By contrast, a combinatorial library approach in which an achiral pre-catalyst combined with several chiral ligand components (L, L, —) may selectively assemble in the presence of several chiral activators (A, A, —) into the most catalytically active and enantioselective activated catalyst (ML A" ) (Scheme 8.16). ... 

Fig. 15. Extended combinatorial multiple-cassette mutagenesis in the evolution of an (S)-selective lipase-variant from P. aeruginosa as a catalyst in the kinetic resolution of 1 (A position 20 A position 161 A position 234 O position 53 position 180 position 272) (49).

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