Peptide‐Cavitands Based on Resorc[4]arenes − Synthesis and Structure

Abstract

AbstractAmino acids and peptides were coupled to the four aminomethyl groups of the bridged resorc[4]arene 2, resulting in peptide cavitands 3 of the general structure 2 [−Aa1‐[Aa2‐[Aa3]]−N(H)R]4. These compounds contain either four amino acids (3a−3d: Aa1 = Gly, Val, Leu or Phe, R = H; 3e, 3f: Aa1 = Gly or Val, R = Z), four dipeptides (3g−3l: Aa1 = Gly, Aa2 = Gly, Val, Leu, Phe, Lys(Boc) or Pro, R = Z), four tripeptides (3m, 3n: Aa1 = Gly, Aa2 = Val, Aa3 = Val or Met, R = Z) or four β‐Ala dipeptides (3o, 3p: Aa1 = β‐Ala, Aa2 = Val or Leu, R = Z). The dipeptide and tripeptide cavitands 3g−3n, which have a glycine bonded to the resorcarene core, form stable inclusion complexes with acetonitrile in chloroform solution. The free energy of complexation exceeds −5.9 kcal mol−1. The exchange between complexed and free acetonitrile molecules is slow on the NMR spectroscopic time scale (298 K). NMR spectroscopic data suggest that the peptides in the acetonitrile complexes of 3g−3n form a cyclic array of hydrogen bonds at the upper rim involving the glycine CO and NH groups. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)