Solution and Solid Phase Synthesis of Unusual a-Amino Acids From

Chapter Si
Solid Phase Synthesis of PHydroxg-PSubstituted-a-Amino Acids
6.1 Introduction
Traditionally, the goal of
cornpounds in as pure a form as
meclicinal chemists has been to produce single
possible for subniission to biological testing and
evaluation as drug candidates. This methodical approach to the development of new drug
entities is tedious, expensive and unavoidably time-consuming.
A combination of necessity as the mother of invention and econornic factors
thereby directed the development of a new method for the rapid synthesis and screening
of compounds, evolving into the field of combinatorial chemistry. In essence,
combinatorial chemistry involves both the synthesis and screening of large groups of
compounds known as Iibrarïes. These techniques have revolutionized the pharmaceutical
industry and are gradually expanding to other fields of the physical sciences. In fact, this
method has been used to produce or optimize lead compounds in many different research
areas and has progressed from its early strategy in generating random librarïes into a
powerful design approach for developing and optimizing potential candidates.'
The primary goal of combinatorial chemistry is the generation of compounds with
a broad stmcturai diversity, the synthesis of which should occur in a precise manner in
order to facilitate screening. Solid-phase organic synthesis, which has many sirnilarities
to solid-phase peptide techniques, therefore uses well-defined organic reactions to
rninimize side-reactions on the solid phase. As such, the purity of the final product after
cleavage off the resin is of paramount importance.
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