Design, synthesis, and characterization of tyrosinophanes, a novel family of aromatic-bridged tyrosine-based cyclodepsipeptides

A simple two-step design strategy has been developed for the synthesis of a large variety of a new class of tyrosine-based aromatic (Ph or Pyr) bridge d cyclodepsipeptides (tyrosinophanes). The design is flexible with respect to the size of the ring and the nature of the bridging unit and permits the incorporation of a variety of amino acid residues inside or outside or bot h inside and outside the ring as illustrated here with the preparation of t yrosine-based macrocycles with aromatic (Ph or Pyr), cage-like alicyclic (a damantane) or simple polymethylene bridging units in ring sizes varying fro m 26-membered to 78-membered and containing leucine residues as part of the ring or. as pendants on the exterior or both inside and outside the macroc yclic ring. H-1 NMR, FT-IR, and CD studies have indicated open-ring structu res for these macrocycles. A noteworthy feature of the strategy is the form ation of the 1 + 1 + 1 + 1 catenane arising from the interlocking of sebaco yl-bridged tyrosine rings. The potential of tyrosinophanes to serve as simp le aromatic hosts in the study of Jr-cation type interactions was illustrat ed with Pyr-bridged macrocycles (6b-8b) using N-methylacridinium hexafluoro phosphate as the pyridinium guest. The K-assoc value with 6b was found to b e 8.95 x 10(3) M-1.