5 Diversity Oriented Synthesis : A Challenge for Synthetic

This article covers the diversity oriented synthesis (DOS) of small molecules in order to generate a collection of pure compounds that are attractive for lead generation in a phenotypic, high throughput screening approach useful for chemical genetics and drug discovery programmes. Nature synthesizes a rich structural diversity of small molecules, however, unfortunately, there are some disadvantages with using natural product sources for diverse small molecule discovery. Nevertheless we have a lot to learn from nature. The efficient chemical synthesis of structural diversity (and complexity) is the aim of DOS. Highlights of this article include a discussion of nature’s and synthetic chemists’ strategies to obtain structural diversity, and an analysis of molecular descriptors used to classify compounds. The assessment of how successful one diversity oriented synthesis is versus another is subjective, therefore we use freely available software (www.cheminformatics.org/diversity) to assess structural diversity in any combinatorial synthesis.