Combinatorial chemistry is among the most recent topics in synthetic organic chemistry. A key feature is diversification in the development of organic reactions and in the synthesis of organic compounds. A crucial chemistry is solid-phase synthesis, which is a powerful method in order to optimize reaction conditions, to investigate scope and limitations of new reactions, and to synthesize a variety of compound libraries. Solid-supports, linkers, and strategies for the combinatorial chemistry are described. Synthetic methods (parallel synthesis and mix-and-split synthesis), analysis, and purification in the solid-phase synthesis are also described.
Combinatorial chemistry has been rapidly recognized as a powerful tool in the domain of synthetic organic chemistry, particularly for the pharmaceutical purpose. This methodology is now being extended to the research field of materials, catalysts, reagents and so on. This review article surveys recent progress of discovery and optimization of organic synthetic methods (development of catalysts, conditions etc.) with diversity-based high-throughput preparation, screening, systems.
The present review surveys basic methodologies for solution-phase combinatorial synthesis by using polymer-supported reagents, scavengers, and phase tagging strategies. Several applications of combinatorial libraries prepared by split & mix synthesis are also described.
Analytical methods for solid phase synthesis are discussed. The advent of combinatorial organic synthesis has accelerated the development of reliable, rapid and sensitive analytical methods for solid phase organic synthesis. Classical colorimetric assays and spectrophotometric-based quantification methods for peptide synthesis are extended to solid phase organic synthesis. The analytical methods familiar to solution-phase synthesis, such as IR spectroscopy, mass spectroscopy, NMR spectroscopy are rapidly adapted for the analysis of solid phase synthesis.
Historically chemical automation was started in the field of analytical chemistry and until around 1992 only a few instrument makers and laboratories had studied the automation of organic synthesis chemistry (1st stage). Along side the growth of combinatorial chemistry, considerable attention has since been paid to developing automated synthesis apparatus and the accompanying peripheral apparatus, especially for the efficient development of new drugs in pharmaceutical companies (2nd stage). Recently many kinds of special-purpose automated modules and units have been developed for solid and solution phase synthesis, especially for high throughput parallel synthesis, isolations and purifications. In this report, I will briefly look at the history of laboratory automation, offer some advice on how to carry it out and then describe some future prospects.