Design, Synthesis, and Characterization of Tyrosinophanes, a Novel Family of Aromatic-Bridged Tyrosine-Based Cyclodepsipeptides.

Abstract

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) bridged 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 both inside and outside the ring as illustrated here with the preparation of tyrosine-based macrocycles with aromatic (Ph or Pyr), cage-like alicyclic (adamantane) or simple polymethylene bridging units in ring sizes varying from 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 macrocyclic ring. (1)H NMR, FT-IR, and CD studies have indicated open-ring structures for these macrocycles. A noteworthy feature of the strategy is the formation of the 1 + 1 + 1 + 1 catenane arising from the interlocking of sebacoyl-bridged tyrosine rings. The potential of tyrosinophanes to serve as simple aromatic hosts in the study of pi-cation type interactions was illustrated with Pyr-bridged macrocycles (6b-8b) using N-methylacridinium hexafluorophosphate as the pyridinium guest. The K(assoc) value with 6b was found to be 8.95 x 10(3) M(-)(1).