| The revolution in biotechnology has changed the process of drug discovery. Biologists now have the ability to assay thousands of compounds per day. This means that the synthesis of new compounds has become the rate limiting step in drug development. In order to increase their productivity, chemists have devised a new technique called combinatorial chemistry. Instead of synthesizing one compound at a time, combinatorial methods allow chemists to synthesize large collections of compounds at one time. Advances in combinatorial technology have the potential to speed the discovery of new drugs as well as other new materials.;Multiple component condensations like the Ugi reaction are ideally suited for combinatorial synthesis. In one step, a chemist can synthesize a diverse library from readily available aldehydes, amines, carboxylic acids and isocyanides. Since the supply of commercially available isocyanides is smaller than the other components, we have developed an efficient method for synthesizing more isocyanides. In this method, the ;Typically, combinatorial chemists must decide between performing a synthesis in solution or on solid support. The following pages discuss a new technique called resin capture in which a chemist can use both the solution and the solid phase in the same synthesis. Resin capture gives a chemist more flexibility because some reactions are better suited to one phase than the other. We have demonstrated the utility of resin capture by synthesizing a series of substituted ethylene derivatives. These derivatives were constructed using the Suzuki reaction both in solution and on solid support. We have also developed a novel silicon linker which has a faster rate of cleavage than previously reported silicon linkers. Using this linker, we have synthesized a library of tamoxifen analogs. Such analogs have the potential to interact selectively with estrogen receptors in different organs. |
