Total structure of hormothamnin A, a toxic cyclic undecapeptide from the tropical marine cyanobacterium hormothamnion enteromorphoides

Article abstract of DOI:10.1016/S0040-4020(01)88753-6

The tropical marine cyanobacterium Hormothamnion enteromorphoides produces a suite of cytotoxic and antimicrobial cyclic peptides. The structure of the most lipophilic of these, hormothamnin A, was determined by interpretation of physical data, principally high NMR and FAB MS, in combination with chemical derivitization and degradation schemes. Isolation of a key pentapeptide fragment DPHE-D-LEU-L-ILE-D-allo-ILE-L-LEU, obtained under partial hydrolysis conditions, was instrumental to the final structure determination. β-D-aminooctanoic acid (D-BAOA) was characterized as a per-ester derivative following complete acid hydrolysis and Z-didehydrohomoalanine (DHHA) was spectroscopically in the intact peptide. The remaining residues (HYPRO, 2 × HSER, GLY) were evident from amino acid and spectroscopic analysis. Sequencing of these residues made use of knowledge from fragments, high field NMR (NOESY and ROESY) and FAB MS analysis of the intact peptide. Absolute stereochemistries of the α-amino residues were determined by HPLC analysis of the acid liberated residues derivatized with Marfey's reagent. The absolute stereochemistry of the β-amino residue was shown by circular dichoroism analysis, HPLC analysis of the Marfey derivative, and chiral synthesis of a homolog. By these techniques, hormothamnin A was demonstrated to possess a cyclo-[D-PHE-D-LEU-L-ILE-D-allo-ILE-L-LEU-GLY-D-BAOA-L-HSER-DHHAL-HYPRO-L-HSER] structure.