Synthesis and Solvent Effects on the Conformation of Hymenistatin 1

The cyclic octapeptide cyclo(‐Pro‐Pro‐Tyr‐Val‐ProLeu‐Ile‐Ile‐) (1), isolated from the Hymeniacidon sponge, was synthesized and examined conformationally using NMR and molecular‐dynamics simulations. Most structural parameters of synthetic 1 are in accord with those reported for the isolated material. Our study indicates some small but significant differences in the assignment of the ¹H‐ and ¹³C‐NMR resonances from those of the natural material. The Conformation was determind in both CHCl3 and DMSO using ¹H‐NMR and molecular‐dynamics simulations. Both NOE's and coupling constants were used as experimental restraints during the simulations which utilized explicitly the same solvent as in the NMR study. The differences in the interaction of the solvent with 1 were examined, providing insight into the observed differenced in conformation. The dominant conformation contains a ßVIa turn about Ile⁸‐Tyr³ including a Pro¹‐Pro² cis‐peptide bond and a ßI or ßII turn about Val⁴‐Ile⁷ in CHCl₃ and DMSO, respectively.