Chemical investigation of an Australian population of the nudibranch Glossodoris atromarginata has yielded three different classes of metabolites from the mollusk; furano diterpene, norsesterterpene and sesterterpene. Ten new furano diterpenes of the spongian series (2.49-2.56, 4.02 & 4.03) and nine new norsesterterpenes (3.53-3.61) were isolated from the current studies. Also reported were the crystal structures and absolute configurations of the three known diterpenes (2.15, 2.39 & 2.41) which have provided a structural insight into the conformational assignment (chair or twisted-boat) in the respective A ring of this suite of tetracyclic diterpenes. The isolation of spongian diterpenoids (e.g. 2.49-2.52) suggested there was a keto-enol tautomerization process being carried out by the nudibranch. The norsesterterpenoids isolated represent a new set of metabolites which have not been previously known to be sequestered by the nudibranch. Further chemical ecological studies of the potential sponge preys secured the diterpenes and norsesterpenes found in the animal were either directly or selectively acquired from the dietary sponges and the observations were consistent with the prey/predator metabolite transfer theory. The isolation of the known sesterterpene 12-deacetoxy-12-oxodeoxoscalarin (2.36) suggests there might not be as much geographical variation in the Australian population of G. atromarginata as previously claimed.
Thirty four new compounds, comprising twenty five cyclic peroxides (5.105, 5.106, 5.112, 5.113, 5.118-5.122, 5.125, 5.126, 6.01, 6.04, 6.05 & 6.21-6.31) with a plakortolide skeleton, four seco-plakortolides (5.107, 5.108, 5.123 & 5.124), three plakortones (5.127, 5.130 & 5.132), the methyl ester derivatives of a didehydroplakinic acid (6.33) and an unusual anhydrosugar (6.44) were isolated from the Australian marine sponge Plakinastrella clathrata Kirkpatrick, 1900. Structural elucidation, including relative configurational assignment, was based on extensive spectroscopic analysis, while the absolute configurations of (5.105, 5.106, 5.112, 5.113 & 6.01) were deduced from 1H 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 △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 ɑ,β-unsaturated lactone intermediate. The NMR data reported for the compound named plakortolide E are inconsistent with the current literature structure and are instead those of the corresponding seco-plakortolide (5.111). Plakortoperoxides A-D (6.05 & 6.21-6.23) each contain a second 1,2-dioxene ring; the cis relative configuration for the side chain endoperoxide ring in plakortoperoxide A (6.05) was determined by a low-temperature NMR study and also by comparison of the chemical shift values with those of reported compounds. An enantioselective HPLC study that compared the natural plakortoperoxide A (6.05) with a synthetic sample prepared from the cyclization of plakortolide P (5.120) with singlet oxygen, revealed the natural sample was a mixture of cis diastereomers at C-15/C-18. Four cyclic peroxides (6.24-6.27) possessed a C9-truncated side chain terminating in a formyl or carboxylic acid functionality, suggesting that these metabolites may have been formed by oxidative cleavage of the △9,10 bond of diene-functionalized plakortolides (e.g.5.19 or 5.120). Finally a group of four metabolites (6.28-6.31) with hydroxy or the rare hydroperoxy functionality unexpectedly revealed a C8 side chain, while the ester (6.33) represents further structural variation within the growing family of cyclic peroxy sponge metabolites. Also isolated was an N-acetylglucosamine-1,3-anhydrosugar (6.44) with the C-3 and C-4 hydroxy groups further substituted by a lactate and a palmitic acids respectively.