Diversity oriented synthesis: a challenge for synthetic chemists.
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.
Bender
A
A
Department of Chemistry, University of Cambridge, UK. ab454@cam.ac.uk
Fergus
S
S
Galloway
W R J D
WR
Glansdorp
F G
FG
Marsden
D M
DM
Nicholson
R L
RL
Spandl
R J
RJ
Thomas
G L
GL
Wyatt
E E
EE
Glen
R C
RC
Spring
D R
DR
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
D004364:Pharmaceutical Preparations