Combinatorial libraries purification

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... 

Scavenger-Based Purification of Combinatorial Libraries Generated... 

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. 

In general, solid-phase synthesis, rather than solution-phase synthesis, can be the preferred method for the generation of combinatorial libraries because of the greater abihty to automate a solid-phase protocol, primarily due to the use of excess reagents in solution to effect cleaner reactions and to the ease of workup by simple filtration. The solid-phase method of peptide synthesis has had many notable successes. However, the preparation of peptides containing more than 20 amino acids in length using the solid-phase technique often causes major problems in that very extensive purification of the final product is needed. 

Parlow, J. J. Naing, W. South, M. S. Flynn, D. L. In Situ Chemical Tagging Tetrafluorophthalic Anhydride as a Sequestration Enabling Reagent (SER) in the Purification of Solution-Phase Combinatorial Libraries, Tetrahedron Lett. 1997, 38, 7959. 

Lead optimization Combinatorial/medicinal chemistry support Open access Purification Combinatorial mixtures Combinatorial libraries-quality control Taylor et al., 1995 Pullen et al., 1995 Zeng and Kassel, 1998 Zeng et al., 1998 Richmond et al., 1999 Yates et al., 2001 Dunayevskiy et al., 1995 Fang et al., 1998 Fitch 1998-1999 FIsu et al., 1999 Dulery et al., 1999 Ventura et al., 2000 Shah et al., 2000... 

Automated synthesis of peptide and oligonucleotide libraries was initiated about 10 years ago [4], Within the last three years, there has been much attention focused on the generation of combinatorial libraries of small molecules. As with biopolymers, the use of solid resin support was central to the advance of this field. In solid-phase synthesis, one of the reactants is covalently bound to the solid support and an excess of the other reactants may be used in each step to drive reactions to completion. Purification of the intermediates and final product is easily achieved through extensive washing of the resin after each chemical step. For the purpose of high throughput synthesis, cleavage of the final... 

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. 

Parlow JJ, Naing W, South MS, Flynn DL, In situ chemical tagging tetrafluorophthalic anhydride as a sequestration enabling reagent (SER) in the purification of solution-phase combinatorial libraries, Tetrahedron Lett., 38 7959-7962, 1997. 

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