Synthesis and properties of Upper-rim C-Linked Peptidocalix[4]arenes

Cone calix[4]arenes, functionalized with two or four 1-alanine or I-phenylalanine units at the upper rim, have been synthesized. These compounds, in which the amino acids are attached to the calix[4]arene macrocycle through their carboxy groups, have been named C-linked peptidocalix[4]arenes. The solubility, conformational, and recognition properties of this novel class of chiral receptors are quite different from those previously reported for N-linked peptidocalix[4]arenes. The tetrafunctionalized phthaloyl derivatives 2 are soluble in low polarity media, whereas the corresponding acetyl and benzoyl derivatives 4 and 5 are completely insoluble in CDCl3, suggesting a high degree of aggregation of the latter compounds. Protonation of the terminal amino groups of 3 results in positively charged water-soluble receptors, which represent the cationic counterparts of negatively charged, water-soluble, N-linked peptidocalix[4]arenes. The difunctionalized acetyl derivatives 9 are soluble in CDCl3 and show a pinched cone conformation, which is mainly determined by intramolecular hydrogen bonding, as revealed by solvent-dependent H-1 NMR spectra and molecular modelling. In contrast to the N-linked analogues, which complex ammonium cations and carboxylic acids, the newly synthesized Clinked peptidocalix[4]arenes interact preferentially with anionic species