Sixteen new compounds, comprising nine new plakortolides K-S (1-9), four seco-plakortolides (10-13), and three plakortones (14-16), were isolated from the Australian sponge Plakinastrella clathrata. Structural elucidation, including relative configurational assignment, was based on extensive spectroscopic analysis, while the absolute configurations of 1-4 were deduced from (1)H NMR analyses on MPA esters derived from Zn/AcOH reduction products. Diastereomeric sets of plakortolides, e.g., K and L, or M and N, differed in configuration at C-3/C-4 rather than at C-6, a stereochemical result that compromises a biosynthetic pathway involving Diels-Alder cycloaddition of molecular oxygen to a Δ(3,5)-diunsaturated fatty acid precursor. The biosynthesis may plausibly involve cyclization of a 6-hydroperoxydienoic acid intermediate following stereospecific introduction of the hydroperoxy group into a polyketide-derived precursor. Isolated seco-plakortolides converted under mild conditions into plakortones with full retention of configuration, suggesting C-6 hydroxy attack on an α,β-unsaturated lactone intermediate. The NMR data reported for the compound named plakortolide E are inconsistent with the current literature structure and are those of the corresponding seco-plakortolide (19). The reported conversion of the metabolite into a plakortone ether on storage is consistent with this structural revision.

Indospicine is a hepatotoxic amino acid found in Indigofera plant spp. and is unusual in that it is not incorporated into protein but accumulates as the free amino acid in the tissues (including muscle) of animals consuming these plants. Dogs are particularly sensitive to indospicine, and secondary poisoning of dogs has occurred from the ingestion of indospicine-contaminated horse meat and more recently camel meat. In central Australia, feral camels are known to consume native Indigofera species, but the prevalence of indospicine residues in their tissues has not previously been investigated. In this study, a method was developed and validated with the use of ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) to determine the level of indospicine in camel meat samples using isotopically labeled indospicine as an internal standard. UPLC-MS/MS analysis showed that the method is reproducible, with high recovery efficiency and a quantitation limit of 0.1 mg/kg. Camel meat samples from the Simpson Desert were largely contaminated (≈50%) by indospicine with levels up to 3.73 mg/kg (fresh weight) determined. However, the majority of samples (95%) contained less than 1 mg/kg indospicine.

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Ten new norscalarane metabolites (1-10) with the mooloolabene skeleton in which the C-8 methyl substituent of a scalarane is replaced by a C-7/C-8 double bond are described from the nudibranch Doriprismatica (= Glossodoris) atromarginata and characterized by extensive 1D and 2D NMR studies, together with MS data. Also isolated was the known scalarane 12-deacetoxy-12-oxo-deoxoscalarin together with 26 furanoterpenes, nine of which (11-19) are reported for the first time. The high diversity of chemical compounds and variation between individuals and locations could reflect a varied sponge diet or an enzymatic detoxification mechanism.

The relative configuration of the plakortolide metabolite (4) isolated from a Madagascan Plakortis sp. and named (+)-plakortolide I is revised following reassignment of the ¹³C signals for C-7 and C-16, thereby establishing that the metabolite isolated was likely (+)-plakortolide E (3). We propose that the name "plakortolide I" should be retained for the plakortolide metabolite 5 first isolated by the Faulkner group; its enantiomer 4 can then be named ent-plakortolide I in line with the description of Barnych and Vatèle. The spectroscopic data for MPA esters prepared from synthetic samples of seco derivatives of plakortolide E (3) and ent-plakortolide I (4) were compared with those of MPA esters of seco derivatives from naturally isolated plakortolides L (1) and K (2) and of seco-plakortolide E (6a). Likewise, the spectroscopic data for MTPA esters derived from 3 and 4 were compared with data for the MTPA esters derived from 5. These various comparisons established that the sign of the specific rotation associated with the natural isolates is an unreliable indicator of absolute configuration and verify that the absolute configurations of plakortolides L (1), K (2), E (3), and I (5) are (3S, 4S, 6S), (3R, 4R, 6S), (3R, 4R, 6R), and (3S, 4S, 6R), respectively.

Sixteen new cyclic peroxides (1-16) with a plakortolide skeleton and the methyl ester derivative of a didehydroplakinic acid (17) were isolated from the Australian sponge Plakinastrella clathrata Kirkpatrick, 1900. Structural elucidation and configurational assignments were based on spectroscopic analysis and comparison with data for previously isolated plakortolides and revealed both phenyl- and methyl-terminating side chains attached to the plakortolide core. Plakortoperoxides A-D (5-8) each contained a second 1,2-dioxine ring; a cis configuration for the side chain endoperoxide ring was determined by a low-temperature NMR study and by comparison of chemical shift values with those of reported compounds. An enantioselective HPLC study compared natural plakortoperoxide A with a synthetic sample prepared by cyclization of plakortolide P with singlet oxygen and revealed that the natural sample was a mixture of cis diastereomers at C-15/C18. Four other cyclic peroxides (9-12) possessed a C(9)-truncated side chain terminating in a formyl or carboxylic acid functionality, suggesting that these metabolites may have been formed by oxidative cleavage of the Δ(9,10) bond of diene-functionalized plakortolides. A final group of four metabolites (13-16) with hydroxy or the rare hydroperoxy functionality unexpectedly revealed a C(8) side chain, while the ester (17) represents further structural variation within the growing family of cyclic peroxy sponge metabolites.

Ingestion of indospicine-contaminated camel and horse meat has caused fatal liver injury to dogs in Australia, and it is currently not known if such contaminated meat may pose a human health risk upon dietary exposure. To date, indospicine-related research has tended to focus on analytical aspects, with little information on post-harvest management of indospicine-contaminated meat. In this study, indospicine degradation was investigated in both aqueous solution and also contaminated meat, under a range of conditions. Aqueous solutions of indospicine and indospicine-contaminated camel meat were microwaved (180 °C) or autoclaved (121 °C) with the addition of food-grade additives [0.05% (v/v) acetic acid or 0.05% (w/v) sodium bicarbonate] for 0, 15, 30, and 60 min. An aqueous sodium bicarbonate solution demonstrated the greatest efficacy in degrading indospicine, with complete degradation after 15 min of heating in a microwave or autoclave; concomitant formation of indospicine degradation products, namely, 2-aminopimelamic and 2-aminopimelic acids, was observed. Similar treatment of indospicine-contaminated camel meat with aqueous sodium bicarbonate resulted in 50% degradation after 15 min of heating in an autoclave and 100% degradation after 15 min of heating in a microwave. The results suggest that thermo-alkaline aqueous treatment has potential as a pragmatic post-harvest handling technique in reducing indospicine levels in indospicine-contaminated meat.