Synthesis of a novel 14-membered highly constrained cyclic peptidic scaffold

The synthesis and NMR analysis of a novel highly constrained scaffold is described. The 14-membered macrocyclic ring structure was inspired by many medicinally relevant natural products that also contain the bi-aryl ether moiety. The synthesis required only commercially available starting materials and involved a base mediated S_NAr cyclization. A conformational search was performed, which indicated a strong preference for a single conformation, which was consistent with observed ROE signals by NMR.