Total synthesis of non-natural compounds for molecular recognition. The double challenge

Molecular recognition of biomolecules by synthetic receptors requires modular assembly of various components to complement the molecular characteristics (sizes, topologies, and functional groups) of the substrate. A number of receptors for biorelevant molecules containing oxoanions have been assembled from a bicyclic chiral guanidine subunit. Several receptors accelerate or catalyze reactions proceeding through anionic transition states. Among the structures recently prepared, a receptor incorporating a calix[6]arene subunit has been developed, showing high affinity for phosphocholine derivatives. Chains of tetraguanidinium sulfates form double helices in solution. These substances strongly induce formation of alpha-helical conformations in Asp rich peptides.