reactions with compounds B 1 ,B 2 and B 3. These simultaneous reactions would
produce a library of nine products. If this process is repeated by reacting these
nine products with three new building blocks (C1–3) a combinatorial library of
27 new products would be obtained.
The reactions used at each stage in such a synthesis normally involve the same
functional groups, that is, the same type of reaction occurs in each case. Very
few libraries have been constructed where different types of reaction are
involved in the same stage. In theory this approach results in the formation of
all the possible products that could be formed. However, in practice some
reactions may not occur.
6.1.1 The design of combinatorial syntheses
One of two general strategies may be followed when designing a combinator-
ial synthesis (Figure 6.3(a) ). In the first case the building blocks are succes-
sively added to the preceding structure so that it grows in only one direction.
It usually relies on the medicinal chemist finding suitable protecting groups
so that the reactions are selective. This design approach is useful if the product
is a polymer (oligomer) formed from a small number of monomeric units.
Alternatively, the synthesis can proceed in different directions from an initial
building block known as atemplate, provided the template has either the
necessary functional groups or they can be generated during the course of
the synthesis (Figure 6.3(b) ). Both routes may require the use of protecting
groups.
AB
A−BA−B−CC
A−B−C−DD(a)A
A−BA−B−CC D
B A−B−C−DA−B−CDDD
(b) D−A−B−CFigure 6.3 (a) The sequential attachment of building blocks. (b) The non-sequential attachment
of building blocks using B as a template
The reactions used when designing a combinatorial sequence shouldideally
satisfy the following criteria:
INTRODUCTION 115