Halipeptins A and B:  Two Novel Potent Anti-inflammatory Cyclic Depsipeptides from the Vanuatu Marine Sponge <i>Haliclona</i> species

Two new metabolites, named halipeptins A and B, have been isolated from the marine sponge <i>Haliclona </i>sp. Their structures were determined by extensive use of one- and two-dimensional NMR experiments, mass spectrometry, and UV and IR spectroscopy. Halipeptin A is a novel 17-membered cyclic depsipeptide, consisting of five residues including two alanines (with l stereochemistry) and three new residues that appear to be previously undescribed from natural sources:  1,2-oxazetidine-4-methyl-4-carboxylic acid, 3-hydroxy-2,2,4-trimethyl-7-methoxydecanoic acid (HTMMD), and <i>N</i>-methyl-δ-hydroxyisoleucine. The HTMMD residue is substituted with 3-hydroxy-2,2,4-trimethyl-7-hydroxydecanoic acid in halipeptin B. Halipeptin A was found to possess very potent anti-inflammatory activity in vivo, causing about 60% inhibition of edema in mice at the dose of 300 μg/kg (i.p.).