Themodernbillion-dollardrug-discoveryprocessstronglyreliesonbothhi- throughput synthesis and
screening methods. Whereas the latter is based on molecular biological methods the ef?cient
and reliable generation of c- pound collections often makes use of combinatorial chemistry.
Discovered in the 1980s this methodology was explored extensively in the 1990s by groups in
academia and in industry. Without any doubt combinatorial chemistry changed the whole
drug-discovery process and found many applications in cropscience and the material sciences.
However since its implementation solution- and solid-phase techniques have been competing
with each other and although many companies started
theircombinatorialchemistryprogramwithsolid-phasetechniques soluti- phase combinatorial methods
have taken over and now account for appro- mately 25% of all combinatorial efforts. The
syntheses of complex non-polymeric structures discovered in the 1960s by the late Bruce
Merri?eld was largely ignored in the context of solid supports mainly due to the fact that
appropriate synthesis techniques were not available. Since solid-phase chemical methodology
strongly differs from traditional solution-phase chemistry two chapters deal with this topic.
The Bräse group (Jung Wiehn Bräse) gives an overview of multifunctional linkers which can
beusedforthegenerationofdiversity-orientedcollections simplybycleavage fromresins. Still in its
infancy solid-phase reactions employ simple amide chemistry in most cases due to their
high-yielding reliable protocols. Ljungdahl Br- ?eld and Kann address solid-phase
organometallic chemistry which is now one ofthe great challenges in reliable solid-phase
organicsynthesis.
