Reagent mixture combinatorial libraries

Two major techniques are generally employed in solid-phase chemistry to generate mixture-based synthetic combinatorial libraries (SCL) of millions of compounds. Multiple functionalities at diverse positions within the library are incorporated either by mixing multiple resins or by using mixtures of incoming reagents. 

The principal difference between the synthesis of individual peptides and peptide libraries is that mixtures of amino acids, rather than individual amino acids, are incorporated into selected or all positions of the sequence of peptide libraries. However, all current peptide chemistry strategies can be used for the synthesis of peptide libraries. In general, library synthesis requires greater emphasis on simplicity and reproducibility of the synthesis process. Although soluble supports have also been used for peptide library synthesis,the majority of methods used to synthesize peptide combinatorial libraries utilize Merrifield s concept of solid-phase synthesis,which is based on the sequential assembly of peptides after covalent attachment of the C-terminal amino acid to a polymeric solid support. This enables the excess of reagents to be removed by simple wash and filtration processes, and avoids the... 

Reagent Mixture Synthesis towards Combinatorial Libraries... 

In the so-called reagent mixture synthetic approach towards combinatorial libraries of compound mixtures, each reaction step of the combinatorial synthesis is carried out with... 

Reagent Mixture Synthesis Towards Combinatorial Libraries 10... 

Recently this approach has been extended to parallel combinatorial library synthesis. One example is the solvent-free synthesis of a 96-member library of substituted pyridines via a one-step Hantzsch-3CC conducted in 96-weU micro titer filter plates (Scheme 2.3-12). Here the p-ketoester and aldehyde reagents were impregnated onto a 5 1 bentonite clay-ammonium nitrate mixture. Irradiation for 5 min in a domestic MW oven, followed by washing the product off the support into a receiver daughter plate gave substituted-pyridine products in >70% purity overall. 

The word library is used to define a collection of compounds usually built around a common structural motif. There are three general approaches to library preparation parallel synthesis, mixture synthesis and split synthesis. One of these preferred strategies, parallel synthesis, is the approach where the compounds are made individually by automated or semi-automated methods. The library members may be made either in solution by classical methods, in solution attached to a polymeric carrier or on solid support. In parallel synthesis there must be linkage to a spatially defined position. The structure of the product is inferred from the position of the reactor and by the order of addition of the synthons and reagents at that position in space. Every possible member, resulting from the combinatorial mix of the synthons, need not be included in the library. 

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