Combinatorial chemistry soluble supports

A related approach, termed dendrimer-supported combinatorial chemistry (DCC), has been disclosed by Kim et al. [23], It uses dendrimers as soluble supports (see Fig. 7). In this case the reactions are performed in solution and the dendrimeric intermediates are isolated/purified by size exclusion chromatography. The strategy was validated by the preparation of a 3 x 3 x 3 combinatorial library using the Fischer indole synthesis. 

The use of dendrimers as soluble supports in combinatorial chemistry was recently introduced by Kim et al. [204] for the synthesis of a 27-member pool library of indoles (three pools by nine individuals). The structure of the dendritic support, which was prepared condensing the commercially available starburst polyamidoamine (PAMAM) dendrimer with the 4-hydroxymethyl benzoic acid (HMB) linker, is given in Figure 7.24. 

While considerable efforts have been spent in the past few years in the field of solid supports for combinatorial chemistry [73], most of them were devoted to modified polystyrenic beads with different sizes, loadings or swelling properties [74], or carrying different functionalities or linkers for library synthesis [75], or to solid supports different from resin beads (pins [76], cellulose [77], soluble supports [78], and so on). Few reports dealt with labelled solid supports prepared by chemical reactions (see the previous paragraphs) and significant efforts in the field of material sciences to obtain intrinsically labeled, nonchemically encoded, easily readable, combinatorial solid supports have not been reported. 

A typical feature of combinatorial synthesis is the use of techniques that facilitate the isolation of products and intermediates. The most common example is the attachment to a solid support, such as a polymer bead, to allow isolation by simple filtration (solid-phase chemistry). A variety of solid and soluble supports have been developed. These may be attached to either the products or the reagents of a library. 

While PEG-based supports are widely used for liquid-phase combinatorial chemistry, other non-PEG-based soluble polymers have also been reported for combinatorial applications. A recent review (276) contains an exhaustive list of homo- and copolym-eric soluble supports used in peptide, oligonucleotide, and oligosaccharide synthesis, including combinatorial chemistry. Two of these supports have also been used for small organic molecule synthesis. Homopolymeric polyvinyl alcohol was used in conjunction with PEG for a protection/derivatization strategy in solution (284), and the copolymer between isopropylacrylamide and acrylic acid was used in the catalytic hydrogenation of a Cbz group (285). 

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... 

Flnorous synthesis An approach to solution-phase synthesis that uses highly niiorinated compounds as soluble. supports for combinatorial chemistry. The addition of water nr organic solvents causes a phase separation of the fluorinatcd support for subsequent cleavage of the synthetic target structure. 

Liquid-phase chemisiry The process of u.sing a large, soluble molecule a.s the support for a combinatorial chemistry experiment. 

A related technique is based on soluble dendrimers as support (dendrimer-supported combinatorial chemistry, [76]). The feasibility of the approach was demonstrated by the synthesis of a small library of indoles. The synthesis started from an a-amino acid that... 

Here we provide a comprehensive review of new task-specific ionic liquids (TSILs) and binary task-specific ionic liquids (BTSILs) as functional ionic liquids designed as alternate soluble supports for supported organic synthesis (SPOS) and combinatorial chemistry. The applications of these supports are based mainly on imida-zolium, ammonium and pyridinium salts. The versatility of the supports has been... 

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