Biomedical Engineering Reference
In-Depth Information
THE BASICS OF
DIVERSITY-ORIENTED SYNTHESIS
KIERON M. G. O'CONNELL, WARREN R. J. D. GALLOWAY, AND
DAVID R. SPRING
1.1
INTRODUCTION
In this chapter, the underlying ideas behind diversity-oriented synthesis are intro-
duced. The relationship between diversity-oriented synthesis and combinatorial
chemistry is discussed, and the rationale behind the use of diversity-oriented synthe-
sis as a tool for the discovery of biologically active molecules is explained. Common
synthetic strategies for the efficient generation of structurally diverse compound col-
lections are then introduced. In the second part of the chapter we discuss recent exam-
ples of diversity-oriented syntheses, with examples taken from our own research and
from the wider community. These examples seek to illustrate the imaginative ways
in which the various synthetic strategies have been implemented and to represent the
current state of the art in diversity-oriented synthesis.
1.2 WHAT IS DIVERSITY-ORIENTED SYNTHESIS?
The term
diversity-oriented synthesis
(DOS) first appeared in the chemical literature
in the year 2000 in an article written by Stuart Schreiber [1]. In this article, which was
written with a particular focus on drug discovery, the term was used to distinguish
between compound libraries (or single compounds) synthesized with the intention of
interacting with preselected protein targets [called
target-oriented synthesis
(TOS)]
and those libraries used in “efforts to identify simultaneously therapeutic protein
