Synthesis and Solvent Effects on the Conformation of Hymenistatin 1

Abstract

Abstract 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 1 H‐ and 13 C‐NMR resonances from those of the natural material. The Conformation was determind in both CHCl3 and DMSO using 1 H‐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 Ile 8 ‐Tyr 3 including a Pro 1 ‐Pro 2 cis ‐peptide bond and a ßI or ßII turn about Val 4 ‐Ile 7 in CHCl 3 and DMSO, respectively.