Efficient approach for the diversity-oriented synthesis of macro-heterocycles on solid-support

The generation of macro-heterocycles starting from resin bound orthogonally protected lysine and using nucleophilic aromatic substitution is described. The method of cyclization required the coupling of o-fluoro-p-nitro benzoic acid followed by intramolecular displacement of the fluoro group. The described method allows a versatile synthetic route to the synthesis of libraries of macro-heterocycles in an attempt to establish lead drug candidates. The desired cyclic products were obtained in good yields and purities.