Library purification techniques

Parlow JJ, Devraj RV, South MS (1999) Solution-phase chemical library synthesis using polymer-assisted purification techniques. Curr Opin Chem Biol 3 320-336... 

This simple and versatile combinatorial one-pot method will surely provide, in future, many diverse libraries, and its use in combination with solution purification techniques (see the next sections) will help in automating the experimental procedures. A thorough search for new multicomponent condensations should even increase their applications in combinatorial library synthesis. 

Despite some obvious limitations as a combinatorial separation method (large volumes of solvents required, cost of multiple automated instruments), the confidence of each synthetic and analytical chemist in LC methods and the extremely high technological level of available instmmentation will keep chromatographic methods among the most popular purification techniques for small-medium solution-phase libraries, especially when large amounts of each crude material are prepared. 

Numerous techniques are available to the organic chemist to support library purification. Zhao et al. [44] published an extensive review on compound library purification strategies, including HPLC, liquid-liquid extraction, solid-supported liquid-liquid extraction, solid-phase extraction, ion-exchange chromatography, and countercurrent chromatography, among others. This... 

The use of solid supports which can be dissolved in many solvents allows one to perform the reactions for library synthesis in a homogeneous medium, but also to separate the intermediates from the reaction solution with common purification techniques (precipitation, crystallization, size-exclusion chromatography, and so on). We will present two examples related to liquid-phase combinatorial syn-... 

The SFC technique is closely related to HPLC, using much the same kind of hardware but with compressed gas such as CO2 as a major component in the mobile phase. Therefore the solvent volume of the purified fraction of the desired product is very small and easily removed, which increases the productivity significantly. More recently supercritical-fluid chromatography (SFC) has begun to show promise as a good technology for purification of the combinatorial library. The technique and applications of SFC are reviewed by several authors. ... 

Both PASP and MAOS are by now recognized as powerful tools by synthetic chemists. The use of both techniques together is somewhat newer and has not yet reached widespread use, as the relatively small number of publications testifies. However, we feel that the examples presented clearly demonstrate how powerful this combination can be, in particular if we keep in mind how complementary these tools are, one simplifying work-up and purification procedures while the other one decreases the reaction time. Considering the ever-increasing interest in the pharmaceutical industry for focused, mediumsized, high purity combinatorial libraries, this combination should attract more and more interest from both academic and industrial laboratories. At the same time, the need to increase productivity should bring synthetic and... 

I High-Throughput Sample Preparation Techniques and Their Application to Bioanalytical Protocols and Purification of Combinatorial Libraries... 

Many of these new techniques are especially suited to the preparation of combinatorial libraries by solution phase parallel synthesis. This chapter provides a brief introduction to the concepts of strategy level purification, and then introduces fluorous chemistry with representative examples of reactions, reagents and techniques. 

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