An Artificial Receptor Based on Monodeoxy Calix[4]arene

Abstract

Synthesis of an artificial receptor (1) based on monodeoxycalix[4]arene as a core structure and its binding behavior to various ureas are presented. The structures of the complexes were predicted by molecular dynamics-molecular mechanics calculations. The difference of the association constants can be explained by the comparison of the structure of the complexes.Recognition of a substrate in a biological receptor is one of the important processes in bioorganic transformations. Host-guest chemistry gives us valuable information about the mechanism of the recognition. 1) In recent studies, a number of artificial receptors and their functions have been reported. 2) Calixarene family plays an important role in the host-guest chemistry. 3) Calix[4]arene, the smallest member of the family, is known to have an ideal cone shape in non-polar solvent due to cyclic hydrogen bonding of four phenolic hydroxyl groups. Ethers of monodeoxycalix[4]arene 4) have several advantages i.e. increased solubility and larger flexibility than calix[4]arene. We focused our attention on the application of the flexible frame of this compound as a host molecule. Hence, we designed the receptor (1) having two benzoic acid moieties as the guest binding portions. Here, we report the synthesis and binding behavior of the receptor, and the molecular modeling consideration of its complexes using molecular mechanics calculation.Synthesis of 1 is started from calix[4]arene (2). 5) Treatment of 2 with methyl iodide in the presence of potassium carbonate gave calix[4]arene monomethyl ether. 6) The monomethyl ether was then treated with diethyl phosphite to afford the phosphate ester. Reductive cleavage of the phosphate group (K/liquid NH 3 , -78°C) gave 3 7) in good yield. Selective iodination at para position of phenol ring using ICl, followed by protection of phenolic hydroxyl groups by methoxymethyl chloride afforded diiodide (4). Introduction of guest binding part was carried out by palladium(0) catalyzed coupling reaction of 4 with 5. 8) Successive hydrolysis of ester function furnished the desired compound (1).It is known that there are three conformers with respect to the orientation of the ether groups in the trialkyl ether of the monodeoxycalix[4]arenes. 9) These conformers can be easily identified by the 1 H-NMR chemical shift values of the ether groups. According to the previously established criteria of the chemical shift change 9) with respect to those of the reference compounds, 2-methoxyxylene and 2-methoxymethoxyxylene, we can conclude that 1 has cone conformation. Hence, the two carboxyl groups of the host arranged in a same side suitable for the effective guest binding by the hydrogen bonds.Binding ability of 1 to a variety of urea guests was evaluated by 1 H-NMR titration technique in CDCl 3 . When added 1 to the guest solution, the N-H signal of propylene urea shifted to down field, suggesting the hydrogen bonding interaction between the N-H of the guest and the carboxyl groups of 1. Job's plot analysis (Fig.1) confirmed the 1:1 stoi...

Synthesis of Peptidocalix[4]arene Libraries and Their Application to the Development of Chemical Sensors for Oligopeptides

“…

Calix [4]arene libraries consisting of ca. 50000 members substituted with peptides at the lower rim were synthesized using encoded spilt synthesis with 15 amino acids.

…”

“…徳島文理大学薬学部（〒770 8514 徳島市山城町西浜傍 示 180） e-mail: hioki＠ph.bunri-u.ac.jp 本総説は，平成 16 年度日本薬学会中国四国支部奨励賞 の受賞を記念して記述したものである． Calix [4]arene libraries consisting of ca. 50000 members substituted with peptides at the lower rim were synthesized using encoded spilt synthesis with 15 amino acids.…”

“…50000 members substituted with peptides at the lower rim were synthesized using encoded spilt synthesis with 15 amino acids. Screening of the library for binding with a dye-labeled oligopeptide indicated that some peptidocalix [4]arenes selectively bind the oligopeptide. The binding constant was estimated to be approximately 2×10 4 mol dm -3 .…”

“…The binding constant was estimated to be approximately 2×10 4 mol dm -3 . In an attempt to develop chemical sensors for peptides, ‰uorescence-labeled peptidocalix [4]arene libraries consisting of ca. 3500 members were synthesized.…”

“…3500 members were synthesized. The ‰uorescence spectrum of peptidocalix [4]arene, which was found in the screening of libraries against the target peptide, was dependent on the concentration of the peptide. The libraries substituted at the upper rim were also synthesized with the aim of developing more selective and sensitive chemical sensors.…”