Richard H. Willis

Studies of Australian soft corals. XXXV

Abstract The in vivo incorporation of mevalonolactone specifically into the terpene portion of a sesquiterpene hydroquinone is reported for the soft coral Sinularia capillosa Eudesma -4 , 7(11)- diene -8β- ol ( 20 ) and the corresponding 8-keto derivative ( 21 ) have been isolated from the soft coral Nephthea species for the first time The aeolid nudibranch Phyllodesmium longicirra was collected when feeding on the soft coral Sarcophyton trocheliophorum and the known diterpene trocheliophorol (25) was found to be concentrated in the cerata of the nudibranch. The absolute stereochemistry of trocheliophorol ( 25 ) has been rigorously determined, and shown to be that previously assigned on spectroscopic grounds

Distribution of foliar formylated phloroglucinol derivatives amongst Eucalyptus species.

Formylated phloroglucinol compounds (FPCs) in Eucalyptus leaves are important determinants of feeding in marsupial folivores and have a wide range of other biological actions. We conducted a survey of the occurrence of formylated phloroglucinol compounds (euglobals, macrocarpals and sideroxylonals) in acetone-petrol extracts of 41 species of Eucalyptus from among seven informal subgenera growing on the East Coast of Australia. We used electrospray ionisation, Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTMS) to search crude extracts of eucalypt leaves for molecular weights characteristic of FPC compounds. We found masses characteristic of reported FPCs in 27 of the 41 species examined. The most frequently identified group of compounds was the sideroxylonals. Notable was the lack of known FPCs in the informal subgenus Monocalyptus.

Sesquiterpene Benzoxazoles and Sesquiterpene Quinones from the Marine Sponge Dactylospongia elegans

A new sesquiterpene benzoxazole, nakijinol B (3), its acetylated derivative, nakijinol B diacetate (6), and two new sesquiterpene quinones, smenospongines B (4) and C (5), were isolated from the methanol extract of the marine sponge Dactylospongia elegans. Also isolated were the known compounds dactyloquinone B and a 1:1 mixture of ilimaquinone and 5-epi-ilimaquinone. Their structures were determined on the basis of spectroscopic analyses and comparison with literature data. The isolated compounds were assessed for their cytotoxicity against a panel of human tumor cell lines (SF-268, H460, MCF-7, and HT-29) and a normal mammalian cell line (CHO-K1). All compounds were found to have activities in the range 1.8-46 μM and lacked selectivity for tumor versus normal cell lines.

Eusynstyelamides A, B, and C, nNOS Inhibitors, from the Ascidian Eusynstyela latericius

Eusynstyelamides A-C (1-3) were isolated from the Great Barrier Reef ascidian Eusynstyela latericius, together with the known metabolites homarine and trigonelline. The structures of 1-3, with relative configurations, were elucidated by interpretation of their spectroscopic data (NMR, MS, UV, IR, and CD). The NMR data of 1 were found to be virtually identical to that reported for eusynstyelamide (4), isolated from E. misakiensis, indicating that a revision of the structure of 4 is needed. Eusynstyelamides A-C exhibited inhibitory activity against neuronal nitric oxide synthase (nNOS), with IC(50) values of 41.7, 4.3, and 5.8 microM, respectively, whereas they were found to be nontoxic toward the three human tumor cell lines MCF-7 (breast), SF-268 (CNS), and H-460 (lung). Compounds 1 and 2 displayed mild inhibitory activity toward Staphylococcus aureus (IC(50) 5.6 and 6.5 mM, respectively) and mild inhibitory activity toward the C(4) plant regulatory enzyme pyruvate phosphate dikinase (PPDK) (IC(50) values of 19 and 20 mM, respectively).

FTICR-MS and LC-UV/MS-SPE-NMR Applications for the Rapid Dereplication of a Crude Extract from the Sponge Ianthella flabelliformis

Dereplication of a methanolic extract of the marine sponge Ianthella flabelliformis using FTICR-MS accurate mass determination and MS(n) techniques enabled rapid and unambiguous detection of a new compound among a plethora of known compounds. Isolation of this compound and the known 19-deoxy analogue using the hyphenated technique LC-UV/MS-SPE-NMR was undertaken, and the structures were confirmed, from a single chromatographic run, as 19-hydroxyaraplysillin-I N(20)-sulfamate (1) and araplysillin-I N(20)-sulfamate (2).

Synthesis of polycarpine, a cytotoxic sulfur-containing alkaloid from the ascidian Polycarpa aurata, and related compounds

Polycarpine 1, a highly cytotoxic marine natural product, has been synthesized in three steps from p-methoxyphenacyl bromide 4 in 57% overall yield. The key reaction for construction of the symmetrically substituted disulfide linkage of polycarpine is the treatment of 2-amino-4-(4-methoxyphenyl)-1-methylimidazole 17 with S2Cl2 in acetic acid. In a similar way ten related compounds, including three thiazole analogues, have been prepared. Most of them exhibit high cytotoxic activities against an array of human cancer cell lines.

Echinoclasterol sulfate phenethylammonium salt, a unique steroid sulfate from the marine sponge, Echinoclathria subhispida

Abstract A phenethylammonium salt of a new steroid sulfate, echinoclasterol sulfate (1) has been isolated from the marine sponge, Echinoclathria subhispida. The structure was determined by interpretation of spectral data including 2D NMR and FABMS. It exhibited antifungal activity against Mortierella ramannianus, and cytotoxicity against PC-9 human lung cancer cells.

Identification of a new human lens UV filter compound.

A new UV filter compound, 4‐(2‐amino‐3‐hydroxyphenyl)‐4‐oxobutanoic acid O‐diglucoside, has been identified in human lenses. The structure suggests that it is a further metabolic product of the second most abundant UV filter compound, 4‐(2‐amino‐3‐hydroxyphenyl)‐4‐oxobutanoic acid O‐glucoside. Quantification studies on the new compound show that it decreases towards zero in both the nucleus and cortex as a function of age. The discovery of this novel disaccharide completes the identification of the major UV filter compounds present in the human lens.

Metachromins U-W: cytotoxic merosesquiterpenoids from an Australian specimen of the sponge Thorecta reticulata.

Three new merosesquiterpenoids, metachromins U, V, and W (1-3), were isolated from a specimen of the marine sponge Thorecta reticulata collected off Hunter Island, Tasmania, Australia. Structures of the new compounds were elucidated through extensive NMR investigations and comparison with literature values. The cytotoxicities of 1-3 were assessed against a panel of human tumor cell lines (SF-268, H460, MCF-7, and HT-29) and a mammalian cell line (CHO-K1). All compounds were found to have 50% growth inhibition activities in the range 2.1-130 μM, with 2 being the most active (GI50 2.1-10 μM).

Comosusols A-D and comosone A: cytotoxic compounds from the brown alga Sporochnus comosus.

Bioassay-guided fractionation of extracts of the brown alga Sporochnus comosus led to the isolation of five new compounds, comosusols A-D (3-6) and comosone A (7). The structures of all isolated compounds were elucidated using standard one- and two-dimensional NMR techniques, as well as comparison with literature values. The cytotoxic activity of all compounds was investigated against a panel of human tumor and mammalian cell lines. These assays found eight of the nine compounds had GI(50) values in the 8-63 μM range.