title: Diversity oriented synthesis: a challenge for synthetic chemists.
abstract: 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 vs another is subjective; therefore we use freely available software (www.cheminformatics.org/diversity) to assess structural diversity in any combinatorial synthesis.
authors.affiliation: Department of Chemistry, University of Cambridge, UK. ab454@cam.ac.uk
authors.forename: A
authors.initials: A
authors.lastname: Bender
authors.forename: S
authors.initials: S
authors.lastname: Fergus
authors.forename: W R J D
authors.initials: WR
authors.lastname: Galloway
authors.forename: F G
authors.initials: FG
authors.lastname: Glansdorp
authors.forename: D M
authors.initials: DM
authors.lastname: Marsden
authors.forename: R L
authors.initials: RL
authors.lastname: Nicholson
authors.forename: R J
authors.initials: RJ
authors.lastname: Spandl
authors.forename: G L
authors.initials: GL
authors.lastname: Thomas
authors.forename: E E
authors.initials: EE
authors.lastname: Wyatt
authors.forename: R C
authors.initials: RC
authors.lastname: Glen
authors.forename: D R
authors.initials: DR
authors.lastname: Spring
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000639:trends*; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D006801:Humans; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D004364:Pharmaceutical Preparations; D010597:Pharmacogenetics / Q000379:methods; D012984:Software
chemical_list: D004364:Pharmaceutical Preparations