Crystal and NMR Structures of a Peptidomimetic β‐Turn That Provides Facile Synthesis of 13‐Membered Cyclic Tetrapeptides

Herein we report the unique conformations adopted by linear and cyclic tetrapeptides (CTPs) containing 2‐aminobenzoic acid (2‐Abz) in solution and as single crystals. The crystal structure of the linear tetrapeptide H₂N‐d ‐Leu‐d ‐Phe‐2‐Abz‐d ‐Ala‐COOH ( 1 ) reveals a novel planar peptidomimetic β‐turn stabilized by three hydrogen bonds and is in agreement with its NMR structure in solution. While CTPs are often synthetically inaccessible or cyclize in poor yield, both 1 and its N ‐Me‐d ‐Phe analogue ( 2 ) adopt pseudo‐cyclic frameworks enabling near quantitative conversion to the corresponding CTPs 3 and 4 . The crystal structure of the N ‐methylated peptide ( 4 ) is the first reported for a CTP containing 2‐Abz and reveals a distinctly planar 13‐membered ring, which is also evident in solution. The N ‐methylation of d ‐Phe results in a peptide bond inversion compared to the conformation of 3 in solution.