Microwave-assisted Combinatorial and High-throughput Synthesis

Microwave-assisted Combinatorial and High-throughput Synthesis 

One of the cornerstones of combinatorial chemistry is solid-phase organic synthesis (SPOS) [2], originally developed by Merrifield in 1963 for the synthesis of peptides [3]. In SPOS, a molecule (scaffold) is attached to a solid support, for example a polymer resin (Fig. 16.1). In general, resins are insoluble base polymers with a linker molecule attached. Spacers are probably included to reduce steric hindrance by the bulk of the resin. Linkers on the other hand are functional moieties, which enable attachment and cleavage of scaffolds under controlled conditions. Subsequent chemistry is then performed on the molecule attached to the support until, at the end of the often multistep synthesis, the desired molecule is released from the support. 

To accelerate reactions and to drive them to completion, a large excess of reagents can be used, because this can easily be removed by filtration and subsequent washing of the solid support. Thus, even final purification of the desired products is simplified, as byproducts formed in solution do not affect the outcome of the target. Nowadays, many linkers and various classic or microwave-assisted cleavage conditions are available, enabling efficient processing of a variety of chemical transformations. 

SPOS can also easily be automated by using appropriate robotics for filtration and evaporation of the reaction mixture to isolate the cleaved product. SPOS can, 

Microwaves in Organic Synthesis, Second edition. Edited by A. Loupy Copyright 2006 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 3-527-31452-0 

---

I 76 Microwave-assisted Combinatorial and High-throughput Synthesis... 

---