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Analytical Methods for Solid and Solution-Phase Combinatorial Chemistry

机译:固相和固相组合化学的分析方法

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NMR and IR are information rich techniques and are generally used during the process of designing and optimising the reaction conditions for library production while HPLC, MS but especially LC-MS are used for quality control of the final library. With the available MS soft ionisation techniques short times of analysis yield up to 400 samples a day, and with the next generation of these instruments, the throughput will be multiplied by a factor of ten. Both automation and the information science have the right state of the art technology to support this jump. With the advent of short and highly efficient columns, LC-techniques have dramatically cut down the analysis times (up to 100-150 samples a day). Semi-preparative version of these columns are also available for sample purification before the biological tests. Moreover the possibility to run parallel analysis with instruments operating on 2 or more columns will, in the near future, increase the efficiency of this technique. CZE (Capillary Zone Electrophoresis) is far to be fully exploited in this field but the possibility to reduce the amount of solvents and samples makes it an attractive technology to be developed in the future. NMR and IR are technologically ready for being routinely used in the high throughput format but the complexity of the data generated at the moment is preventing the possibility to have an automated and reliable data analysis system. In case of solid-phase library production, the application of on bead-IR and HR-MAS NMR techniques will give information for the choice of resin, solvent and reaction condition and the throughput will be higher with the use of sample changer for the MAS probes. If the libraries are of solution-state samples, the large number of compounds could be analysed with automated high-throughput NMR spectroscopy using a LC-NMR probe but the interpretation of the collected data is still a bottleneck. Moreover the amount of information these techniques can generate and the potentiality to run analysis on resins and even in the reaction tubes makes them widely employed in combinatorial chemistry.
机译:NMR和IR是信息丰富的技术,通常用于设计和优化用于文库生产的反应条件的过程中,而HPLC,MS(尤其是LC-MS)则用于最终文库的质量控制。借助现有的MS软电离技术,短时间的分析每天就可产生多达400个样品,而使用这些新一代仪器,通量将提高十倍。自动化和信息科学都拥有正确的最新技术来支持这一飞跃。随着短而高效的色谱柱的问世,液相色谱技术极大地缩短了分析时间(每天最多100-150个样品)。这些色谱柱的半制备形式也可用于生物学测试之前的样品纯化。此外,在不久的将来,使用在2根或更多根色谱柱上运行的仪器进行并行分析的可能性将提高该技术的效率。 CZE(毛细管区带电泳)在该领域尚待充分开发,但减少溶剂和样品量的可能性使其成为将来发展的诱人技术。 NMR和IR在技术上已准备好以常规方式以高通量格式使用,但目前生成的数据的复杂性阻止了拥有自动化且可靠的数据分析系统的可能性。在固相库生产的情况下,在珠式IR和HR-MAS NMR技术上的应用将为树脂,溶剂和反应条件的选择提供信息,而使用MAS的样品更换器,通量将更高探针。如果库是溶液状态的样品,则可以使用LC-NMR探针通过自动高通量NMR光谱分析大量化合物,但收集数据的解释仍然是瓶颈。此外,这些技术可以产生的信息量以及对树脂甚至在反应管中进行分析的潜力使得它们在组合化学中得到了广泛的应用。

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