Structure and conformation of peptides containing the sulfonamide junction II. Synthesis and conformation of cyclo[-MeTau-Phe-DPro-]

By applying the method of amino-acyl incorporation to sulfonamido peptides, cyclo(-MeTau-Phe-DPro-) 3 has been synthesized in high yield starting from Z-MeTau-Phe-Pro-OH. The crystal structure and the molecular conformation of 3 have been determined. Crystals are orthorhombic, s.g. P2₁2₁2₁, with a = 5.454, b = 13.486, c = 24.025 Å. The structure has been solved by direct methods and refined to R = 0.039 for 1974 reflections with I > 1.50 σ(I). The 10-membered cyclopeptide adopts a backbone conformation in the crystals characterized by Phe-DPro and DPro-MeTau peptide bonds in trans and cis conformation, respectively. Both the peptide bonds deviate significantly from planarity and the corresponding |δω| values are ca. 12°. The sulfonamide SO₂NH junction adopts a cisoidal conformation with a C^α₁- S₁-N₂- C₂^α torsion angle of 70.8°. ¹³C n.m.r. data show that the trans geometry at the Phe-DPro junction found in the crystals is retained in DMSO solution. The 10-membered ring of 3 is characterized by a pseudo mirror-plane passing through the Phe nitrogen and the DPrO carbonylic carbon. The DPrO ring adopts a half-chair conformation. The Phe side chain conformation corresponds to the statistically most favored g^? rotamer (χ¹= - 68.6°). The crystal packing is characterized by a weak intermolecular hydrogen bond between the NH group and the MeTau O₁’ oxygen.