Strategy and Tactics in Combinatorial Organic Synthesis. Applications to Drug Discovery

A strategic analysis of various issues which pertain to the enablement of combinatorial organic synthesis to produce libraries of non-polymeric organic molecules is given. Methods and examples of the development of solid-phase organic chemistry and its subsequent application to combinatorial library synthesis for drug discovery is illustrated with successful case studies. The synthetic versatility of resin-bound amino-acid-derived imine intermediates to produces, β-sultams and pyridines is shown. Use of natural products as key components for creation of combinatorial libraries is presented using Rauwolfia alkaloids and the cephalosporin nucleus as examples