Modular Introduction of endo-Binding Sites in a Macrocyclic Cavity towards Selective Recognition of Neutral Azacycles

Macrocycles with a functionalized interior, which is a general cavity feature of bioreceptors, are relatively hard to synthesize. Here we report a modular strategy to customize diverse endo-binding sites in the macrocycle cavity. Only two steps are needed. First, one V-shaped functional module bearing an embedded binding site and two 2,5-dimethoxyphenyls as reaction modules are connected. Then the condensation of the resulting monomer and paraformaldehyde directly produces the designed macrocycle. V-shaped monomers are deliberately used to guarantee the binding sites equatorially directing inward into the cavity and 2,5-dimethoxyphenyls standing axially as macrocycle sidewalls. More than a dozen endo-functionalized macrocyclic receptors have been constructed. Host-guest complexation studies show that macrocycle BP1-decorated interior OH moieties can strongly encapsulate neutral azacycles by forming inner hydrogen bonds, giving a high association constant of 4.59x10(4) M-1 in non-polar media.