A steroid-based receptor for unprotected amino acids: the enantioselective recognition of L-tryptophan

A cholapod receptor possessing urea binding sites at C3, C7, and C12 positions and with an intrinsic chiral structure was synthesized, and the binding abilities toward amino acids in both L- and D- forms (Trp, Phe, Leu, and Ala) were studied using H-1 NMR spectroscopy, UV-vis spectroscopy and computer simulation. Changes in H-1 NMR spectra of the receptor revealed that complexation with amino acids occurred via hydrogen bonding and CH-pi interactions. Binding to tryptophan was especially strong, and was found to be enantioselective (K-a=480 M-1 for L-Trp, 260 M-1 for D-Trp). NOESY and computer simulations were used to investigate the structures of the diastereomeric complexes between the receptor and the tryptophan enantiomers. In the case of L-Trp the carboxylate group bound at the two ureas adjacent to C7 and C12, while D-Trp was positioned closer to the urea adjacent to C3. (C) 2010 Elsevier Ltd. All rights reserved.