ABSTRACT
The purpose of this chapter is to provide useful details concerning the application of microwaves to the optimization of combinatorial preparation of small-mole cule organic compounds in solutions as well as on solid supports. Our results presented here demonstrate that the presence of microwaves greatly improves the rate of chemical reactions, which is critical to high throughput library synthe sis, not only with a large reduction of reaction time but also without altering the final yield (1-11). This chapter also discusses the use of capillary electrophoresis (CE) in assessing stereoisomers formed during the combinatorial synthesis. In combinatorial chemistry, issues such as reaction stereoselectivity and possible racemization during reactions are rarely mentioned in the literature, and these are vital to the quality of the libraries prepared (12). Using tetrahydro-p-carbolines as examples, we demonstrate the usefulness of CE in enantiomeric separation of stereoisomers and rapid quantitative measurement of their corresponding isomer ratios as well as in assessing reaction racemization for its overall potential in library optimization.
