Supports and linkers

Most solid-state combinatorial chemistry is conducted by using polymer beads 10 to 7.50 jum in diameter. These beads 

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Key fsi, solid support and linker P, unique protecting group X, activating group indicates a uniquely differentiated hydroxyl group... 

Support-bound aldehydes or ketones can be reduced to alcohols under mild reaction conditions that are compatible with most supports and linkers. Typical reducing agents are sodium borohydride or diisobutylaluminum hydride, which can penetrate cross-linked polystyrene provided that a solvent with sufficient swelling ability is... 

The conditions used for final cleavage of the peptide from the support depend on the type of support and linker chosen. Because side-chain protective groups must also be removed, the use of scavengers is required during cleavage to avoid alkylation of the peptide. 

When the target molecule is similar to known structures, or when a sound synthetic scheme is drawn, the assessment of the best experimental conditions in solution is straightforward, while the transfer of a reaction sequence onto SP requires more theoretical (selection of the best support and linker) and experimental work to find appropriate reaction conditions. 

In conclusion, the concept of solid-supported chemistry has been extended from the preparation of peptides and other biomolecules to any organic molecule. PS-and PEG-based resins are the most widely used however, syntheses can be carried out in any solid support. The development of new solid supports and linkers/ handles is crucial to fulfill the new requirements of modem drag discovery programs. 

In side-chain anchoring the amino acid side-chain is linked to the solid support and the C- and N-termini are orthogonally protected. Once chain elongation is finished, deprotection of both ends and subsequent cyclization and cleavage delivers the final cyclized product. Numerous amino acids have been used for side-chain anchoring, including Asx/Glx [155-161], Lys/Orn [158, 162], Ser/Thr [159, 163], Tyr [159, 163, 164], His [165, 166] and Cys [167, 168], on the usual supports and linkers for peptide synthesis (Figure 18.12). 

Figure 19.16 Supports and linkers for the soluble polymer supported oligonucleotide synthesis.

Table 1 Solid Supports and Linkers with Reactive Halogens... 

Similarly to insoluble supports, molecules are attached via a linker unit (see Chapter 1.7) to the support. Supports and linkers have to be chemically compatible with the reaction conditions employed for the library synthesis. Conversely, the final products have to be releasable without chemical modifications. Soluble supports have been successfully used for ... 

Recently, the increasing popularity of boronic acids as synthetic intermediates has motivated the development of solid supports and linkers to allow their immobihza-tion and facilitate purification operations or derivatization (Figure 1.29). The appeal of these methods is particularly apparent in view of the difficulties often encountered in isolating pure boronic acids from both aqueous and organic solvent systems. 

Gr0tli and coworkers used various resin supports and linkers and employed thermal heating or microwaves to turn dipeptides into DKPs (Scheme 9 1). They found that PEGA-Ser resin is a good choice with water as the solvent under thermal heating for the formation of DKPs, while for microwave reactions, other solid supports in toluene /-butanol (1 4) or /-BuOH, or toluene at 120°C, also performed very well. 

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