Solid-phase synthesis of a novel peptide substituted calix[4]arene

The described approach provides calix[4]arene scaffolds that can be coupled to amino acids using standard solid phase peptide synthesis, providing a route for the rapid preparation of combinatorial libraries of this class of molecular hosts. In addition, we report the first example of a tetrapeptido-calix[4] arene in which the amino acids are attached to the upper rim through the carboxy termini. Specifically, a tetra-nitrocalix[4]arene was prepared, attached to solid support, and the nitro groups were reduced to the corresponding amines by treatment with SnCl2.H2O. This was followed by three successive couplings with alanine to provide the tetra(trialanine)calix[4]arene. The final product was cleaved from the solid support and shown by LCMS to elute as one peak with the expected mass.