Journal
NATURAL PRODUCT REPORTS
Volume 25, Issue 4, Pages 719-737Publisher
ROYAL SOC CHEMISTRY
DOI: 10.1039/b706296f
Keywords
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Funding
- EPSRC
- Wellcome Trust
- GSK
- AstraZeneca
- Engineering and Physical Sciences Research Council [GR/S99419/01, GR/S99426/01] Funding Source: researchfish
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The purpose of diversity-oriented synthesis is to drive the discovery of small molecules with previously unknown biological functions. Natural products necessarily populate biologically relevant chemical space, since they bind both their biosynthetic enzymes and their target macromolecules. Natural product families are, therefore, libraries of pre-validated, functionally diverse structures in which individual compounds selectively modulate unrelated macromolecular targets. This review describes examples of diversity-oriented syntheses which have, to some extent, been inspired by the structures of natural products. Particular emphasis is placed on innovations that allow the synthesis of compound libraries that, like natural products, are skeletally diverse. Mimicking the broad structural features of natural products may allow the discovery of compounds that modulate the functions of macromolecules for which ligands are not known. The ability of innovations in diversity-oriented synthesis to deliver such compounds is critically assessed.
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