Analysis and prediction of combinatorial chemistry synthesis and screening data.

The goal of combinatorial chemistry is to simultaneously synthesize sets of compounds possessing properties that are then distinguished through screening. As the size of a compound set increases, data analysis becomes more challenging. Analysis of Variance (ANOVA) is an accepted statistical method that offers a straightforward solution to this problem. Two steps encountered by combinatorial scientists appear well suited to ANOVA: the prediction of synthetic outcomes (purity and yield) of set members and the analysis of screening data to identify combinations of reagent inputs that result in molecules with a desired property. To illustrate, a subset of a combinatorial array, referred to as a reaction rehearsal set, is evaluated to create a model predictive of the individual synthetic outcomes of the full matrix. In a second exercise, the biochemical screening data obtained from a combinatorial library is analyzed to identify reagent interactions that result in molecules possessing the sought activity.

Microwave-assisted solid-phase synthesis (MASS): parallel and combinatorial chemical library synthesis.

The use of microwave technology in solid-phase organic synthesis has attracted much attention in recent years. The combination of solid support, either as a medium for chemical synthesis or as a carrier for organic reagents, with microwave heating offers several advantages over conventional techniques. Rapid and elevated heating of reaction mixtures can induce the completion of chemical transformations in minutes while several hours or days may be required for the same chemistry under conventional conditions. With decreased time of exposure to high temperatures and lessened thermal degradation, microwave accelerated chemistries often deliver products of higher purity when compared to conventional heating techniques. Several chemical syntheses on solid-phase employing microwave irradiation have been reported in the literature. The reagents, solvents, and equipment selected for microwave-mediated synthesis are important contributors to the success of the chemical transformation. Owing to the timesavings in performing chemical synthesis under microwave irradiation, the technique has become an emerging partner in solid-phase organic synthesis.