Synthesis and properties of upper rim C-linked peptidocalix[4]arenes

Cone calix[4]arenes, functionalized with two or four 1-alanine or I-phenyla lanine units at the upper rim, have been synthesized. These compounds, in w hich the amino acids are attached to the calix[4]arene macrocycle through t heir carboxy groups, have been named C-linked peptidocalix[4]arenes. The so lubility, 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 ter minal amino groups of 3 results in positively charged water-soluble recepto rs, which represent the cationic counterparts of negatively charged, water- soluble, N-linked peptidocalix[4]arenes. The difunctionalized acetyl deriva tives 9 are soluble in CDCl3 and show a pinched cone conformation, which is mainly determined by intramolecular hydrogen bonding, as revealed by solve nt-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 wit h anionic species,