Automated solution-phase parallel

In contrast to the large number of advantages of solution-phase parallel synthesis, there is one major disadvantage, namely the purification problem . Given that solution- and solid-phase sample manipulation are both convenient and easily automated, the limitation to solution-phase parallel synthesis is the isolation of the desired compounds. Thus, the throughput attainable in automated solution-phase synthesis is directly related to the work-up procedures and to the purification process. Therefore, easy and efficient purification methodologies are required for highspeed solution-phase synthesis. 

If small or medium libraries for lead optimization are demanded and all synthetic products are to be screened individually, most often parallel synthesis is the method of choice. Parallel syntheses can be conducted in solution, on solid phase, with polymer-assisted solution phase syntheses or with a combination of several of these methods. Preferably, parallel syntheses are automated, either employing integrated synthesis robots or by automation of single steps such as washing, isolation, or identification. The latter concept often allows a more flexible and less expensive automation of parallel synthesis. 

Kirschning A, Monenschein H, Wittenberg R (2001) Functionalized polymers - emerging versatile tools for solution-phase chemistry and automated parallel synthesis. Angew Chem Int Ed 40 650-679... 

Solution-phase combinatorial synthesis provides a homogeneous reaction medium and overcomes the drawbacks of a solid-phase strategy. An easy and reliable purification method is required in solution-phase combinatorial (parallel) synthesis to facihtate automation. The throughput in solution-phase automated synthesis is directly related to the facility of performing a purification process (work-up), compound separation, etc.15... 

Antonenko VV, Manual and automated parallel synthesis of individual compounds. Presented at Strategic Research Institute s Symposium, Solid and Solution Phase Combinatorial Synthesis, New Orleans, LA, April 28-29, 1997. 

These libraries contain a relatively small number of individuals (typically tens to hundreds) and are almost always prepared as discrete libraries using parallel synthesis and automated or semiautomated devices. Focused libraries are predominantly prepared in solution because of the easier shift from classical organic synthesis to solution-phase combinatorial chemistry, while automated purification procedures for relatively small arrays of discrete compounds in solution are common nowadays. The... 

Kuroda, N., Hattori, T., Fujioka, Y., Cork, D. G., Kitada, C., and Sugawara, T. (2001) Application of automated synthesis suite to parallel solution-phase peptide synthesis. Chem. Pharm. Bull. Tokyo 49, 1147-1154. 

SH DeWitt. Automated parallel purification methods. Solid and Solution Phase Combinatorial Synthesis, New Orleans, 1997. 

Solid-phase parallel synthesis mimics the previously described solution phase strategy. This approach easily lends itself to both semi- and full automation. In contrast to the solution phase method, purification is easily achieved by simply washing the resin beads, and the reactions can be driven to completion by excess reagents, multiple cycles, and microwave techniques. The initial building block or scaffold is attached to the resin bead by a detachable linker. At the end of the synthesis, the final construct is released under the appropriate cleavage conditions for automated purification, usually by high-pressure liquid chromatography (HPLC). This allows bioanalysis of the final product in aqueous solution under standard assay conditions. 

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