Solid phase synthesis is a synthetic method commonly used for the construction of peptides. This approach is also useful with the synthesis of peptide-like organic molecules. There are numerous ways to synthetically construct peptidomimetic molecules, but solid phase synthesis provides an efficient way, over more traditional chemistry, when time for long synthesis is not available and smaller yields are desired for analysis. Many factors must be considered before constructing peptidomimetics on a 2-chlorotrityl polystyrene resin. The greatest advantage of this approach is the fact that it does not require lengthy purification columns after each step. After coupling the resin beads are washed with excess solvent, concentrated down and are then ready for the next coupling reaction. This approach can expedite the synthetic process and there are many techniques and recommendations to optimize the best yields. Unlike peptide synthesis, it is imperative to use anhydrous solvents in the synthetic construction. This review article will discuss the techniques and recommendations when using 2-chlorotrityl chloride resin to construct peptidomimetics when the C-terminus is a carboxylic acid.

Keywords: 2-Chlorotrityl Chloride Resin; Peptidomimetics; Solid Phase Synthesis; Solid Phase Techniques; Tri-Methyl Silyl Chloride;