High-throughput chemistry

Bailey D, Brown D. High-throughput chemistry and structure-based design survival of the smartest. Dmg Discovery Today 2001 6 57-59. 

The palladium-catalyzed Heck carbonylation reaction is a powerful means of generating amides, esters, and carboxylic acids from aryl halides or pseudohalides [28]. The development of rapid, reliable, and convenient procedures for the introduction of carbonyl groups is important for the development of high throughput chemistry in general and high-speed microwave-mediated chemistry in particular. Unfortunately, the traditional method of introducing carbon monoxide into a reaction mixture via a balloon or gas tube is not practical because of the special requirements of microwave synthesis. 

This modification proved generally applicable and the Suzuki reaction is arguably the most versatile of modern cross-coupling reactions. The reaction has, for example, attracted the interest of groups involved in high-throughput chemistry, because a large variety of boronic acids are commercially available. 

Key words High-throughput chemistry, chemical library, random library, targeted library, optimization library, library design, biological activity, drug discovery. 

Several features of palladium-catalyzed carbon-carbon bond formation reactions are attractive in high-throughput chemistry. These reactions tend to be... 

In a lead refinement paradigm, one relies on empiricisms that are sometimes formalized in models such as QSARs and pharmacophores, or sometimes encoded in the mind of an experienced medicinal chemist. The compounds made in a lead refinement experiment tend to be even more focused on a given region of property space, and this may require different chemistries in order to access. The types of structural modifications suggested to be beneficial may not however be amenable to high-throughput chemistry, nor may the starting materials be available. 

Combined with expedient purification techniques (e.g., scavengers, reagents on solid support, and solid phase extraction techniques) [ 14], microwave-assisted synthesis is leading the way towards genuine high-throughput chemistry that will hopefully ease the chemistry-related bottleneck in the drug development process. 

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