Synthesis and Chemical Structure of the Cyclic Heptapeptide Stylissamide H

We investigated the chemical structures and conformational isomers of the cyclic heptapeptides stylissamide H and euryjanicin A isolated from marine sources. Despite sharing the same molecular structure, stylissamide H and euryjanicin A exhibit different conformational isomers in solution and solid states. The main difference arises from the <i>cis/trans</i> configurations of the two Pro residues. We prepared stylissamide H using Fmoc solid-phase peptide synthesis and investigated its chemical structure in the solution state and the solid state via NMR spectroscopy and X-ray crystallography, respectively. The results indicated that the <i>s</i>-<i>trans</i>,<i>cis</i>Pro conformer of stylissamide H is more stable in solution, whereas the <i>s</i>-<i>cis,cis</i>Pro conformer is more stable in the solid state. We concluded that stylissamide H and euryjanicin A are the same molecules.