Biomedical Engineering Reference
In-Depth Information
SOLID-PHASE SYNTHESIS ENABLING
CHEMICAL DIVERSITY
NAD E ZDA CANKA ROV A AND VIKTOR KRCH N AK
7.1
INTRODUCTION
Is solid-phase synthesis more suitable than solution-phase synthesis for the prepa-
ration of diverse molecules? This is a textbook example of a wrong question. Both
solution-phase and solid-phase synthesis are tools. It is the goal of the project that
guides the decision as to which tool is more appropriate. Thus, numerous factors
have to be taken into consideration, and each must be considered and weighted to
make the final decision. We listed several relevant features in Table 7.1. Purposely,
without considering their significance, the final numerical count of pros (underlined)
and cons (in italics) in the table is shown as a tie. However, each item bears a dif-
ferent importance for any particular project, and thus weighting them is critical for
the final choice. The operational simplicity of solid-phase synthesis and the potential
to pool structurally diverse polymer-supported intermediates for a reaction with the
same reagent makes solid-phase synthesis an attractive alternative, particularly with
respect to the synthesis of combinatorial libraries possessing a large number of indi-
vidual compounds. Successful solid-phase synthesis requires careful optimization of
reaction conditions for a respectful set of diverse building blocks. Taking this fact into
account, chemists very often tend to attempt exploiting the same type of resin-bound
intermediate (particularly those with more than one diversity position) for the syn-
thesis of structurally unrelated heterocycles. Vivid old examples are 1,2-diamines:
N
-alkylated
o
-phenylenediamines can be converted to several different fused rings,
