N-linked peptidocalix[4]arene bisureas as enantioselective receptors for amino acid derivatives.
Bisurea calix[4]arenes 1 and 2 possessing L-amino acid moieties at the lower rim were synthesized by reaction of the methyl esters of glycine, L-alanine, or L-isoleucine with the appropriate isocyanate (12 or 13), obtained with a safe and efficient Curtius rearrangement from the corresponding carboxylic acid derivatives. The conformational properties of the ligands 1 and 2 were investigated by means of a combined NMR and molecular modeling study which evidences that they are deeply influenced by strong intramolecular H-bonds between the urea NH groups and the vicinal phenolic oxygen atoms or the opposite urea C=O group. Complexation studies performed by ESI-MS and NMR spectroscopy in acetone solution show that the binding ability of these bisurea hosts decreases by increasing the side chain size of the amino acid. Host 2b has a remarkable binding ability for the N-acetyl-D-phenylalaninate anion with an interesting enantioselectivity (KDass/KLass=4.14), which is explained on the basis of a three-point interaction mode of binding.
Yakovenko
Anton V
AV
Institute of Organic Chemistry, National Academy of Sciences of Ukraine, Murmanskaya str. 5, 02660 Kyiv, Ukraine.
Boyko
Vyacheslav I
VI
Kalchenko
Vitaly I
VI
Baldini
Laura
L
Casnati
Alessandro
A
Sansone
Francesco
F
Ungaro
Rocco
R
D000596:Amino Acids / Q000737:chemistry* / Q000378:metabolism*; D000838:Anions; D001665:Binding Sites; D047250:Calixarenes / Q000737:chemistry*; D002625:Chemistry, Organic / Q000379:methods*; D006859:Hydrogen / Q000737:chemistry; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D010636:Phenols / Q000737:chemistry*; D010649:Phenylalanine / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism; D014508:Urea / Q000737:chemistry
D000596:Amino Acids; D000838:Anions; D008024:Ligands; D010455:Peptides; D010636:Phenols; C121325:calix(4)arene; D047250:Calixarenes; D010649:Phenylalanine; D006859:Hydrogen; D014508:Urea; C044228:N-acetylphenylalanine