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Dual Linkers and Analytical Constructs

One of the most time-consuming steps in synthesis on solid supports is the adaptation and optimization of reaction conditions. Furthermore, the optimization process is difficult to monitor on the solid support. Magic-angle spinning NMR (MAS) or FT-IR can be used, but these are technically very demanding. A possible solution is the concept of dual linkers involving an analytical unit [200]. These can be employed not only to optimize chemical reactions on a support, but also for quality control of the compound libraries. The basic principle is outlined in Fig. 15. [Pg.101]

It involves the use of two orthogonal linkers, namely linker 1 and linker 2. The analytical unit is placed between the two linkers and the desired compound is attached to linker 2. Analytical units commonly used today comprise a chromophore, a mass ionizer, and a peak splitter. Cleavage at linker 1 releases the desired [Pg.101]

Despite these efforts, an exact determination of the relative amounts of compounds was not possible. This led to the development of analytical constructs of type 181 (Fig. 16) containing chromophores that are suited for the facile detection and quantification of compounds in mixtures [202, 203]. Commonly used chromophores for this purpose are dansyl and anthracenyl units. Both of these chromophores allow the detection of products at the single-bead level. [Pg.102]

The suitability of linker 181 was demonstrated in the synthesis of a fibrinogen antagonist. During each reaction step, the efficiency could be monitored and the purity of the final product could be assessed in a straightforward way [203]. [Pg.103]

Recently, a convenient preparation of an analytical construct of type 182 (Fig. 17) has been reported. The synthesis of 182 is possible without a need for extensive chromatography. Furthermore, the deuterium mass tag can be incorporated vhth D2O in a cost-effective manner [204]. [Pg.103]


See other pages where Dual Linkers and Analytical Constructs is mentioned: [Pg.101]    [Pg.101]    [Pg.103]   


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