Combinatorial Chem

What is Combinatorial Chemistry?

Merrifield's solid-phase synthesis (SPS) concept, first developed for biopolymer synthesis, has spread in every field where organic synthesis is involved. Many laboratories and companies focused on the development of technologies and chemistry suitable to SPS. This resulted in the spectacular outburst of automated high-throughput synthesis and combinatorial chemistry, which profoundly changed the approach for new drugs, new catalysts, or new materials discovery. High-volume synthesis strategies will invariably require that intermediate reaction products be isolable from reaction solutions without resort to crystallization, chromatography, or solvent evaporation. The fastest and simplest method of isolating a substance from a liquid, such as a solution of reactants, is filtration. Of course, filtration is possible only when the substance is a solid. This, then, is the rationale for growing organic compounds on an insoluble polymer matrix. It is a motivating force sufficient to overcome even the inherent, potent aversion most chemists have to conducting reactions with heterogeneous reactants, and it was precisely the motivation for the development of solid-phase peptide synthesis 30 years ago by Merrifield. Because polypeptide synthesis can involve hundreds of reactions in series, simple product isolation is as necessary as for combinatorial synthesis that involves hundreds of reactions in parallel. The ease of intermediate product isolation brings two important benefits to each type of synthesis. First, excess reagent can be used with the frequent effect of driving recalcitrant reactions toward completion. Second, the advantages of automation can now be brought to bear on the repetitive aspects of the synthesis. Polypeptides and polynucleotides are today synthesized almost exclusively via automated systems employing solid-supported chemistries. Although presently less developed, combinatorial chemistry already benefits from automation, and it is a certainty that this will increase.

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