Templates solid supported

The use of templates supported on polymer beads can become a very useful tool for the development of synthetic receptors through the dynamic combinatorial approach. Since the template is attached to a solid support, the untemplated species will eventually become washed from the solid support by filtration leaving only strong binders appended to the beads. The species attached to the solid phase may be washed off under different solvent conditions that disrupt the template-receptor interaction and subsequently identified. The development of selection techniques using guests appended to polymer beads is pivotal to the management and success of highly diverse DCLs of receptors. 

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Figure 3.6 Amplification of the best receptor induced by a solid supported template.

Scheme 3.7 Amplification and isolation of receptors from a DCL using a solid supported template.

In addition, the strategy also provides a high-yield synthetic method for the selected receptor. The use of reversible chemistry under thermodynamic control in combination with solid supported templates may speed up this time-consuming step in the discovery process of new receptors. 

As a unichiral template which is used as a stationary phase itself, or which is bonded to a solid support (silica particles or fused silica capillaries). 

Most examples discussed so far made use of amorphous inorganic supports or sol-gel processed hybrid polymers. Highly disperse materials have recently become accessible via standard processes and, as a result, materials with various controlled particle size, pore diameter are now available. Micelle-templated synthesis of inorganic materials leads to mesoporous materials such as MCM-41, MCM-48, MSU, and these have been extensively used as solid supports for catalysis [52]. Modifications of the polarity of the material can increase the reactivity of the embedded centre, or can decrease its susceptibility to deactivation. In rare cases, enhanced stereo- or even... 

Figure 7.8 General scheme of the SPREAD procedure of self-replication, (a) A template is immobilized by an irreversible reaction with the surface of a solid support, (b) The template binds complementary fragments from solution, (c) The fragments are linked together by chemical ligation, (d) The copy is released, and re-immobilized at another part of the solid support to become a template for the next cycle of steps. Irreversible immobilization of template molecules is thus a means to overcome product inhibition. (Adapted from Luther et al, 1998.)...

A solid-phase synthesis of furo[3,2-3]pyran derivatives utilizing highly functionalized sugar templates has been reported <2003JOC9406>. After incorporation of alkenes within the sugar template, such as compound 95, the solid support is introduced via formation of the acid amide. This immobilized system then allows a ruthenium-catalyzed ring-closing metathesis that leads to the formation of the fused oxacycles. 

Schreiber and co-workers have shown that this approach is useful in the preparation of compound libraries. One of their examples is a diversity-oriented synthesis of polycyclic scaffolds through the Perrier reaction followed by the PKR of a glycal template on solid support (Equation (35)). 

Applications of Suzuki and Heck cross-coupling reactions were adopted by Gallop and coworkers [131] to prepare diverse biaryl- and styryl-substituted (3-lactams on solid support. The catalyst system, [PdCl2(dppf)]-TEA, was found to be efficient to promote C-C bond formation around a (3-lactam template (Schemes 26 and 27). 

As shown in template 91, a linker group can be attached to the tricyclic skeleton which results in the possibility to graft the template onto a solid support and synthesize template-bridged cyclic petide libraries using the split-and-mix method. 

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