Contents In many scientific fields, including biology, medicine, and especially in the pharmaceutical chemistry, it is highly desirable to have available a large number of individual organic compounds that are structurally related. With such a library, a scientist can compare the properties of these materials and, by doing so, reveal how the chemical structure affects these properties. Such a structure-activity relationship (SAR) is at the heart of combinatorial chemistry, which provides efficient methods for the preparation of these libraries. Not only can such a library provide the compounds that are needed for a given application, but it can also act as a predictive tool, suggesting how to improve the properties of a given organic compound, regardless of the final application. Several fundamentally different methods are available for making these libraries, and the method of choice will often depend on both the size and quality of the library being generated. 0-8493-0815-1/04/$0.00+$ 1.50
In this chapter, the various combinatorial chemistry techniques will be introduced, surveyed and analyzed. References for detailed experimental procedures are provided at the end of the chapter. Since many of the readers of this handbook may have primarily a biological or medical background, an attempt has been made to describe the chemistry involved here with them in mind. Note that for those who may require a chemical library for their research, there are many alternatives to inhouse synthesis. For commercially available chemicals, these may be simply purchased from several available suppliers. Structure-based search programs for commercially available compounds are particularly helpful in this regard. There is also a small but growing list of suppliers that specialize in small quantities of otherwise unavailable compounds for the generation of chemical libraries. The next step up is to consider contract synthesis in order to have a library prepared by a company that specializes in combinatorial library preparation. This can be an expensive proposition, but it may be a viable alternative when no in-house capability exists. Lists of commercial chemical suppliers, as well as combinatorial chemical suppliers, are provided as an appendix to this chapter. The remainder of this chapter is for those who wish to perform combinatorial chemistry at their own facility.