Synthesis and Properties of Upper Rim C-Linked Peptidocalix[4]arenes

• Published in: European journal of organic chemistry Vol. 2001; no. 3; pp. 595 - 602
• Main Authors: Lazzarotto, Marcio, Sansone, Francesco, Baldini, Laura, Casnati, Alessandro, Cozzini, Pietro, Ungaro, Rocco
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag GmbH 01-02-2001; WILEY‐VCH Verlag GmbH
• Subjects: Amino acids; Anion binding; Calixarenes; Chiral hosts; Supramolecular chemistry
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/1099-0690(200102)2001:3<595::AID-EJOC595>3.0.CO;2-#

Cone calix[4]arenes, functionalized with two or four L‐alanine or L‐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 1H NMR spectra and molecular modelling. In contrast to the N‐linked analogues, which complex ammonium cations and carboxylic acids, the newly synthesized C‐linked peptidocalix[4]arenes interact preferentially with anionic species.