Development Using Synphase Crowns

Expanding the variety and properties of linker groups increases the scope of practical applications of radiation-grafted polymer surfaces for the parallel synthesis of organic compounds. Linker molecules have a bearing on the types of reactions that can be performed and the ease of isolation of products after cleavage. 

A wide range of linker groups are currently used with SynPhase crowns. They accommodate formation of the following functional groups upon cleavage carboxylic acids, primary and secondary amides, sulfonamides, alcohols, phenols, amines, anilines, anilides, hydroxymates, aldehydes, ketones, and thiols. 

An important criteria in solid-phase synthesis is product purities immediately after cleavage from the support. Ideally, the target compound should be cleaved into a solvent-reagent system that can be easily removed, usually by evaporation. Solvents/cleavage reagents that are difficult to remove may compromise subsequent biological screening of the libraries. Consequently, 

This section outlines useful strategies for preparing aldehydes and hy-droxamic acids that were developed on SynPhase crowns. 

Superior attachment conditions were identified as 0.1 M aldehyde in methanol with 1% N Pr2Et for 2 h at 60°C these gave 90% incorporation. Additional experiments showed that the N Pr2Et additive was not required. 

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SynPhase crowns may be used to perform large numbers of optimization reactions in parallel. This library of reaction conditions may be analyzed by assaying product purities after cleavage from the solid phase using high-throughput techniques such as HPLC and ESMS. Overall, this approach can greatly reduce the time required for this critical step of compound library development. 

Mimotopes has been involved in the development, use, and commercialization of radiation-grafted polymer surfaces for multiple parallel synthesis since the late 1980s.10-12 Although other workers have reported the use of radiation-graft polymers in solid-phase synthesis,13,14 as far as we are aware, the graft polymer devices manufactured and sold by Mimotopes (SynPhase Crowns, SynPhase Lanterns) are the only current commercial products of this type. These products are presented in Fig. 1. The SynPhase Lanterns are the current design for small molecule synthesis. The initial... 

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