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SYNTHETIC CHEMISTRY
An upfront investment
Organic synthesis plays a leading role in the discovery of small molecules for the exploration of biological systems. Therefore, the development of efficient strategies for the preparation of these molecules is a necessary aspect of the small-molecule approach to chemical biology.
Damian W Young
The use of small molecules to interrogate normal or disease-associated biological processes is
an important tactic of modern chemical biology1. The strategy most commonly used today is rooted in the assemblyof collections of small molecules for screening against a variety of specic biomolecular targets or in phenotypic assays. However, deciding which molecules to include within a screening collection and where to obtain these substances constitute key intellectual challenges in
this area. The eld of synthetic organic chemistry has played a pivotal role in recent years in providing molecules with valuable biological properties. Chemists today are using increasingly sophisticated methodologies and synthetic pathways aimed at creating small molecules forthe specic purpose of biological probe development. This is exemplied in a paper by Werz and coworkers in this issue, which describes a creative solution toward the synthesis of a biologically relevant group of small molecules2.
In the early years, molecules produced by nature were the principal supply of biologically active substances. Although natural products continue to be a valuable source of interesting small molecules,it is now becoming evident that nature does not completely own the domainof biologically active, small molecules. The fruits of creative modern organic synthesis of non-natural small molecules have given rise to a host of useful small-molecule probes that otherwise might never have been produced on the earth3.
2010 Nature America, Inc. All rights reserved.
Chroman (13 examples)
Chroman (13 examples)
a
b
Ph
Ph
O
Br Ph
O
O
O
O
O
O
Palladium catalyst
Palladium cat
cataly
alyst
st
O
O
C4
C4
C4
O
Br
O
O
Br
Br
Ph
Ph
Ph
O
OH
O
O
O
O
Bromoglycal building block
3rd C-C bond
3rd C-C bond
Palladium C-Br
insertion
Palladium C-Br
insertion
D
Dom
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p oocees
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Domino reaction process
[Pd]
Ph
O
O
O
O
O
O
[Pd]
P
O
O
O
O
O
O
[Pd]
O
[Pd]
Ph
Ph
Ph
Pd