MS-Analysis of an Isoxazoline-Library

Synthesis of the isoxazoline library [59] was performed on 2-chlorotritylchloride resin. The resin was loaded with diethylphosphonoacetic acid and the polymer-bound phospho-nate reacted with aldehydes to yield substituted E-cinnamic esters or substituted E-acrylic esters. This was followed by a 1,3-dipolar cyclo-addition with nitrileoxides, synthesized via the method of Mukaiyama and Floshinoc [60] (Fig. 17.18). In this reaction, two regioi-somers are formed, each of which exist in two enantiomeric forms. Table 17.4 shows the building blocks used in the library synthesis. 

2 HPLC-Analysis in Positive and Negative Ion Scan Mode 

For the analysis of both single compounds and compound libraries, it is advisable, as mentioned above, to employ both positive and negative scan modes. For the case of HPLC-MS-analysis this requires that TFA, widely used as a solvent additive, be replaced by another acid, e.g., formic acid. Experience has shown that formic acid is suitable for the majority of separations. In some cases, minor peak broadening is observed in comparison to TFA. 

The manual investigation and interpretation of such complicated chromatograms is a very time-consuming enterprise. To facilitate the evaluation of HPLC-chromatograms there are several software-aided methods available, the two main methods being the extract-ion -function and the landscape -plot. 

For libraries with an upper mass limit of approximately 500 amu, GC-MS can prove advantageous. Capillary-GC on fused silica capillaries is characterized by high separation power and the ability to analyze relatively polar substances. In many cases, the problems of tailing, thermal instability and volatility associated with excessive analyte polarity can be overcome by the use of derivatization techniques. 

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