Purification, combinatorial chemistry

Chapters 1 and 2 have been reorganised and updated in line with recent developments. A new chapter on the Future of Purification has been added. It outlines developments in syntheses on solid supports, combinatorial chemistry as well as the use of ionic liquids for chemical reactions and reactions in fluorous media. These technologies are becoming increasingly useful and popular so much so that many future commercially available substances will most probably be prepared using these procedures. Consequently, a knowledge of their basic principles will be helpful in many purification methods of the future. 

Tietze and coworkers developed two new domino approaches in the field of combinatorial chemistry, which are of interest for the synthesis of bioactive compounds. Combinatorial chemistry can be performed either on solid phase or in solution using parallel synthesis. The former approach has the advantage that purification of the products is simple and an excess of reagents can be used. This is not possible for reactions in solution, but on the other hand all known transformations can be used. The Tietze group has now developed a protocol which combines the... 

One of the cornerstones of combinatorial synthesis has been the development of solid-phase organic synthesis (SPOS) based on the original Merrifield method for peptide preparation [19]. Because transformations on insoluble polymer supports should enable chemical reactions to be driven to completion and enable simple product purification by filtration, combinatorial chemistry has been primarily performed by SPOS [19-23], Nonetheless, solid-phase synthesis has several shortcomings, because of the nature of heterogeneous reaction conditions. Nonlinear kinetic behavior, slow reaction, solvation problems, and degradation of the polymer support, because of the long reactions, are some of the problems typically experienced in SPOS. It is, therefore, not surprising that the first applications of microwave-assisted solid-phase synthesis were reported as early 1992 [24],... 

B. Yan (Ed.), Analysis and Purification Methods in Combinatorial Chemistry, Wiley Interscience, Hoboken, 2004. 

Roming, T.S., Bell, C., and Drolet, D.W., Aptamer affinity chromatography Combinatorial chemistry applied to protein purification, J. Chromatogr. B, 731, 275-284, 1999. 

Small sample preparation. For synthetic PFCs, this means synthesizing either a large amount of very small samples ( libraries ) obtained by combinatorial chemistry, or regular-size PFC samples for the use as drug candidates (respectively for their synthesis), for preparing impurities, metabolites, and other compounds. For natural PFCs it involves product extraction, purification, and characterization. 

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... 

The main problem with preparing libraries using solution chemistry is the difficulty of removing unwanted impurities at each step in the synthesis. Consequently, many of the strategies used for the preparation of libraries using solution chemistry are directed to the purification of the products of each steps of the synthesis. This and other practical problems has usually restricted the use of solution combinatorial chemistry to synthetic pathways consisting of two or three steps. 

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