Synthesis and host-guest studies of chiral N-linked peptidoresorc[4]arenes

Four cone resorc[4]arene octamethyl ethers (10, 11, ent-10, and ent-11) tetrafunctionalized at the feet with valyl-leucine [LL- (6); DD- (ent-6)] and leucyl-valine [LL- (9); DD- (ent-9)] methyl esters have been synthesized. These compounds, obtained by conjugation of macrocycle tetracarboxylic acid chlorides with the appropriate terminal amino groups of the above dipeptides, are N-linked peptidoresorc[4]arenes. We found that these macrocycles (M) are capable of recognizing the homologue dipeptides as guests (G), both in solution and in the gas phase, by forming relatively stable host-guest complexes ([M.G]), resistant to chromatographic purification but not to heating. Complexation phenomena between M and G in solution were investigated by NMR methods, including NMR DOSY experiments, for the detection of translational diffusion. Heteroassociation constants of 2030 and 186 M(-1) were obtained by the Foster-Fyfe method for the complexes [10.6] and [10.ent-6], respectively, the latter being comparable to the self-association constant of dipeptide itself. Conversely, the structural features of the proton-bound complexes [M.H.Gn]+ (n = 1, 2), generated in the gas phase by electrospray ionization mass spectrometry (ESI-MS), were investigated by collision-induced dissociation (CID) experiments. In both cases, the four N-linked peptidoresorc[4]arenes were shown to act as synthetic receptors and to recognize the homologue dipeptide by means of hydrogen bonds.