A single specimen of Hexabranchus sanguineus, a nudibranch from the Indo-Pacific that is known to sequester kabiramides B, C and other trisoxazole macrolides, yielded new kabiramide analogs – 9-desmethylkabiramide B and 33-methyltetrahydrohalichondramide – and two new unexpected thiazole-containing cyclic peptides in sub-micromole amounts. The structures of these cyclic peptides were determined by analyses of 1D and 2D NMR spectra recorded with a state-of-the-art 1-mm 1H NMR high-temperature superconducting micro-cryoprobe, together with mass spectra. In addition to two proline residues, each peptide contains a thiazole- or oxazole-modified amino acid residue, together with conventional amino acid residues. All of the amino acid residues were L- as determined by Marfey’s analysis of the acid hydrolysates of the peptides. This is the first report of cyclic thiazole peptides from H. sanguineus. Since thiazole-oxazole modified peptides are typically associated with cyanobacteria and tunicates, the finding may imply a dietary component of the H. sanguineus that was previously overlooked.

Following our first report on elevated polybrominated diphenyl ether (PBDE) concentrations in California women, we expanded our investigation to include diverse groups of local women. We analyzed additional adipose and serum samples collected in the late 1990s from San Francisco Bay Area women participating in a breast cancer study and in a reproductive study, respectively. Adipose samples (n = 32) were analyzed by low-resolution mass spectrometry in negative-ion chemical ionization mode, whereas serum samples (n = 50) were analyzed by dual-column gas chromatography with electron capture detection. The results confirmed our earlier findings. Concentrations of 2,2´,4,4´-tetrabromodiphenyl ether (BDE-47) in contemporary California women ranged between 5 and 510 ng/g lipid, with a median (16.5 ng/g lipid) 3-10 times higher than those reported from Europe. In contrast, PBDEs were not measurable in any of 420 archived serum samples collected in the 1960s from San Francisco Bay Area women participating in a study of child development. BDE-47 concentrations did not increase with age or with concentrations of a polychlorinated biphenyl (PCB-153), suggesting other routes of exposure in addition to diet. Rising body burdens of endocrine-disrupting chemicals such as PBDEs may pose a potential public health threat.

Two new highly polar brominated spiroisoxazolines, araplysillin N 9 -sulfamate (1) and an N-[5S, 10R)-7,9-dibromo-10-hydroxy-8-methoxy-1-oxa-2-azaspiro[4.5]deca-2,6,8-triene-3-carboxy]-4-aminobutanoic acid (2), were isolated from a sample of Aplysina fulva collected in the Florida Keys. The absolute stereostructures of the new compounds were determined from analysis of MS, 1 H and 13 C NMR and CD spectroscopy. Compound 2 provides a structural clue that may unify the biosynthesis of brominated spiroisoxazolines.Secondary metabolites from sponges of the Order Verongidae 1 are typically highly oxidized compounds derived from bromotyrosine. Modified alkaloids derived from 3′,5′-dibromotyrosine (Figure 1, i, R = H) have been found from various Verongid genera 2 -mainly Aplysina, Psammaplysilla, Pseudoceratina and Verongia 3 -that are widely distributed throughout Mediterranean, Pacific and Atlantic waters. 4 Heterocycles based on brominated spiro-isoxazolines (Figure 1, iii, R=H, (5S,10R)-7,9-dibromo-10-hydroxy-8-methoxy-1-oxa-2-azaspiro[4.5]deca-2,6,8-triene-3-carboxamide) are common natural products arising from bromotyrosine secondary metabolism. 5 Since the first example of a spiroisoxazoline was reported by the Minale group from two Mediterranean species, Aplysina aerophoba and Verongia thiona ,6 over 25 spiroisoxazoline analogs have been described. 4Recently, we reported geographic variability of the diastereomeric compositions of fistularin-3 and 11-epi-fistularin-3 in Aplysina species collected from Brazil and the USA (Florida Keys) and Agelas from Australia (the Great Barrier Reef). 7 We have extended these investigations and now report two new polar water-soluble spiroisoxazolines -the sulfamate 1 and carboxylic acid 2. Both compounds occur in very low concentrations in the most polar fractions derived from column chromatography of methanol-soluble components of the sponge extract. Compound 2 is a lower homolog of purpuroceratic acid (5), 8 reported by Kijoa and coworkers, and lacks the unusual aryl C-methyl group of the latter. Compound 1 is the N-sulfato derivative of the known compound araplysillin-1 (3) and is formally the decarboxylation product of the N-sulfato α-aminoacid, ianthesine D (5), reported by Okamoto et al. from Ianthella sp. 9 Carboxylic acids 2 and 5 may provide a "missing link" that unifies the biosynthesis of several spiroisoxazoline alkaloids from Verongid sponges. with a 1-oxa-2-azaspirodecatriene-ring system as seen in the structures of aeroplysinin-1 10 fistularin-3, 12 and related compounds. NMR signals were observed (Table 1) for other units including a 1,3-disubstituted propane chain terminated with an oxygen atom and an NH(CO) group, and an 1-aryl-2-ethylamine side chain.A database survey (MarinLit, University of Canterbury) of known Verongid sponge compounds, matched the expected formula (with the assumption of one SO 3 group) to a monosulfated derivative of araplysillin-1 (3). 11 Verification of this assignment came from 13 C NMR chemical shifts of 1 (Table 1) which ma...