ABSTRACT
Parallel synthesis methods have evolved in order to keep pace with developments in the search for therapeutic lead compounds by high-throughput screening. Thus, synthesis techniques for generating compound mixtures or arrays of single compounds have become an integral part of combinatorial chemistry [1-6] and its application to drug discovery. Solid-phase synthesis [7 -16] is a key component of high-throughput synthesis because compounds anchored to a solid support can be treated with large excesses of reactants to drive reactions to completion. The resin-bound product can then be purified by a simple solvent wash to remove excess reactants, other reagents, and any high-boiling solvents. Moreover, there are several examples [7,8] of cyclization reactions that have been shown to be more efficient when conducted on a polymeric solid support than in solution, where oligomerizations compete readily. This is generally attributed to site isolation [17], a feature that also permits the solid support to act as a protecting group for one of two identical functional groups in the same molecule. Solid-phase synthesis is also readily automated, and a number of synthesis instruments are commercially available [16,18]. The creation of defined libraries from a single aliquot of resin by the mix and split method [19-22] further improves throughput if sensitive and/or on-bead screening methods for mixtures are available and appropriate deconvolution methods can be used.
