ABSTRACT
New combinatorial synthetic methods, both solid-phase and solution-phase, now allow the expeditious preparation of organic compound arrays (1-11). In the context of an ongoing development program, ChemRx Advanced Technologies has devised a number of solution-phase and solid-phase spatially separated smallmolecule libraries for screening against a broad range of biological targets. Adapting carbon-carbon and carbon-heteroatom bond-forming reactions for array synthesis has been our primary focus.*
The use of solid phase has been a central feature of combinatorial chemistry. Peptide synthesis on polystyrene supports produced the field of combinatorial chemistry. For peptides and DNA synthesis, a large variety of solid supports from controlled pore glass to cellulose in cotton have been used (12,13). Small-molecule combinatorial chemistry has focused almost entirely on polystyrene-based resins (14,15). We have used polystyrene almost exclusively to generate spatially sepa rated diversity libraries of 5000 compounds with greater than 50 (imol per well.
