Synthesis and Structure of Chiral Cone Calix[4]Arenes Functionalized at the Upper Rim with L-Alanine Units

Synthetic routes were developed to Link L-alanine methyl ester or L-alanyl-L-alanine methyl ester at the upper rim of calix[4]arenes blocked in the cone conformation. Several tetra- (3 and 6) and difunctionalized (11 and 12) amino acids containing macrocycles were obtained. Reaction of these compounds with hydrazine gave the corresponding hydrazido derivatives 4, 13, and 14, while the hydrolysis of 3 with LiOH produced the tetraacid 5 whose lithium salt is water soluble at neutral pH. The structural properties of all amino acids containing calix[4]arenes were studied by mono- and bidimensional H-1 NMR experiments. The X-ray crystal structure of the difunctionalized receptor 11 shows three different conformations in the solid state, none of them having intrachain hydrogen bonding.