Solid‐Phase Synthesis and Combinatorial Approaches to Peptidomimetics

Together with the growth of applications in the field of peptide chemistry, increasing interest in applying solid-phase chemistry to organic synthesis occurred in the 1990s, together with the rise of combinatorial chemistry as a novel approach for the generation of large libraries of compounds. A common approach for the synthesis of peptidomimetic scaffolds on a solid phase has focused on translating the concepts of solid-phase peptide synthesis (SPPS) to the panorama of organic synthesis. Iminium chemistry is an important approach to scaffolds possessing amino acid moieties in the field of peptidomimetics, taking advantage of the amino and the carbonyl groups of the amino acids. The Pictet-Spengler reaction is a straightforward way to achieve conformationally constrained scaffolds by taking advantage of iminium chemistry.