Solid-Phase Synthesis of Peptides, Peptidomimetics, and Cyclic Peptides Using Traceless Aromatic Side-Chain Tethered Building Blocks

Combinatorial chemistry, combined with recent advances in robotic screening, which enable the testing of a large number of compounds in a short period of time, is becoming an important tool in accelerating drug discovery. This technique involves the preparation of a large number of structurally related compounds either as mixtures in the same reaction vessel or individually by parallel synthesis. In this manner large pools of similar compounds can be synthesized within a short period of time. Combinatorial libraries have been prepared using both solution chemistry and by solid phase synthesis; however, solid phase synthesis allows the use of excess reagents to drive the reaction to completion and easy removal of the reagents and side-products by simple filtration of the polymeric support and washing with solvent. Therefore, solid phase synthesis offers a more attractive approach to the generation of chemical libraries for screening purposes.