Synthesis of Chemical Libraries

The challenge in the synthesis of chemical libraries is the vast number of different, potentially drug-like small molecules which is estimated to be as high as 1060. As all of these molecules can never be synthesized and tested, it is essential to define criteria for the composition of libraries spanning the biologically relevant areas of the chemical space most efficiently. An important criterion of a compound library is its chemical diversity, a term describing the similarity or dissimilarity of all library components. Thus, chemical diversity expresses how well a library represents all theoretical possibilities within the chemical property space. A library with low... 

Scheme 23 Synthesis of chemical libraries of focused PDF inhibitors...

Gordon, E.M. Strategies in the design and synthesis of chemical libraries. In... 

The synthesis of chemical libraries loaded with structural diversity is an emerging field with direct applications in biomedical research. Strategies for library synthesis have mainly focused on combinatorial synthesis of molecules that vary substituents with a core... 

This new resin makes it possible to produce custom aldehydes and ketones from a wide range of carboxylic acids, including A-Boc-amino acids. No alcohol side product is observed, and the purity of the resulting aldehyde or ketone is so high that it may be used directly as a building block in parallel synthesis of chemical libraries. 

K., Chao, B., Ito, S., Clark, J., Coner, C., Waller, C., Kuki, A. PGVL Hub an integrated desktop tool for medicinal chemists to streamline design and synthesis of chemical libraries and singleton compounds, in (Zhou, J. Z., ed.) Chemical Library Design. Humana Press, New York, Chapter 15. 

PGVL Hub An Integrated Desktop Tool for Medicinal Chemists to Streamline Design and Synthesis of Chemical Libraries and Singleton Compounds... 

Cheng, S. Comer, D. D. Williams, J. P. Myers, P. L. Boger, D. L. Novel Solution Phase Strategy for the Synthesis of Chemical Libraries Containing Small Organic Molecules, /. Am. Chem. Soc. 1996,118, 2567. 

Gayo, L. M. Suto, M. J. Ion-Exchange Resins for Solution Phase Parallel Synthesis of Chemical Libraries, Tetrahedron Lett. 1997,38, 513. 

During the past few years, polymer-assisted solution-phase synthesis has become the prevalent method for the parallel synthesis of chemical libraries as confirmed by the increasing number of publications and reviews on the subject.16-29 A key step in the parallel solution-phase combinatorial... 

Combinatorial chemistry has proven its usefulness for the synthesis of chemical libraries, with different degrees of complexity embedded in the scaffolds and/or the building blocks used. The synthesis of polyfunctionalized molecules in... 

Cheng S, Comer DD, Williams JP, Myers PL, Boger DL, Novel solution phase strategy for the synthesis of chemical libraries containing small organic molecules, J. Am. Chem. Soc., 118 2567-2573, 1996. 

Gayo LM, Suto MJ, Ion-exchange resins for solution phase parallel synthesis of chemical libraries, Tetrahedron Lett., 38 513-516, 1997. 

Rivero RA, Greco MN, Maryanoff BE, Equipment for the high-throughput organic synthesis of chemical libraries, In Czarnik AW, DeWitt SH, eds., A Practical Guide to Combinatorial Chemistry, Washington, DC, American Chemical Society, pp. 281-307, 1997. 

CD Garr, JR Peterson, L Schultz, AR Oliver, TL Underiner, RD Cramer, AM Ferguson, MS Lawless, and DE Patterson. Solution phase synthesis of chemical libraries for lead discovery. J Biomol Screen 1 179-186, 1996. 

Products/technologies Screening and synthesis of chemical libraries, high-throughput assay development, and lead validation. 

However, another reason why flash chemistry is needed is that our way of synthesizing compounds is currently changing. For example, combinatorial synthesis of chemical libraries has become very popular in academia and industry and on-site, on-demand synthesis is expected to be popular in the future. These new trends in chemical synthesis increase the demand for flash chemistry. 

In an interesting development for combinatorial chemistry, Sm -promoted radical cyclizations have been adapted for use on solid support [27], The procedures developed have some inherent advantages over -Bu3SnH-mediated reactions and sometimes even to the corresponding solution phase SmE-promoted reactions. Unfortunately, they still appear to lack the consistency necessary for general use in the synthesis of chemical libraries. 

S Cheng, CM Tarby, DD Comer, et al. A solution-phase strategy for the synthesis of chemical libraries containig small organic molecules a universal and dipeptide mimetics template. Bioorg Med Chem 4 727-737, 1996. 

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