Rhodocomatulin-Type Anthraquinones from the Australian Marine Invertebrates <i>Clathria hirsuta</i> and <i>Comatula rotalaria</i>

Chemical investigations of an Australian sponge, <i>Clathria hirsuta</i>, from the Great Barrier Reef, have resulted in the isolation of two known anthraquinones, rhodocomatulin 5,7-dimethyl ether (<b>1</b>) and rhodocomatulin 7-methyl ether (<b>2</b>). Additionally, four new anthraquinone metabolites, 6-methoxy­rhodocomatulin 7-methyl ether, 3-bromo-6-methoxy-12-desethyl­rhodocomatulin 7-methyl ether, 3-bromo-6-methoxy­rhodocomatulin 7-methyl ether, and 3-bromo­rhodocomatulin 7-methyl ether (<b>3</b>–<b>6</b>), were also isolated and characterized. This is the first report of the rhodocomatulin-type anthraquinones from a marine sponge, as <b>1</b> and <b>2</b> were previously isolated from the marine crinoid genus <i>Comatula</i>. An additional chemical investigation of the marine crinoid <i>Comatula rotalaria</i> enabled the isolation of further quantities of <b>1</b> and <b>2</b>, as well as two additional new crinoid metabolites, 12-desethyl­rhodocomatulin 5,7-dimethyl ether and 12-desethyl­rhodocomatulin 7-methyl ether (<b>7</b> and <b>8</b>). An NMR spectroscopic analysis of compounds <b>7</b> and <b>8</b> provided further insight into the rhodocomatulin planar structure and, together with the successful implementation of DFT-NMR calculations, confirmed that the rhodocomatulin metabolites existed as <i>para</i> rather than <i>ortho</i> quinones

<i>ent</i>-Labdane Diterpenes from the Stems of <i>Mallotus japonicus</i>

Eight new <i>ent</i>-labdane diterpenoids, mallonicusins A–H (<b>1</b>–<b>8</b>), were isolated from the stems of <i>Mallotus japonicus</i>. Their structures, including the absolute configurations, were determined by extensive analyses of spectroscopic data and the ECD spectra of the Pr­(FOD)₃ complex of substrates in CCl₄. The absolute configuration of compound <b>1</b> was confirmed by single-crystal X-ray crystallography using Cu Kα radiation

A Grand Challenge: Unbiased Phenotypic Function of Metabolites from <i>Jaspis splendens</i> against Parkinson’s Disease

A grand challenge in natural product chemistry is to determine the biological effects of all natural products. A phenotypic approach is frequently used for determining the activity of a compound and its potential impact on a disease state. Chemical investigation of a specimen of <i>Jaspis splendens</i> collected from the Great Barrier Reef resulted in the isolation of a new pterin derivative, jaspterin (<b>1</b>), a new bisindole alkaloid, splendamide (<b>2</b>), and a new imidazole alkaloid, jaspnin A (<b>3</b>) TFA salt. Jaspamycin (<b>8</b>) and 6-bromo-1<i>H</i>-indole-3-carboximidamide (<b>16</b>) are reported for the first time as naturally occurring metabolites. Known nucleosides (<b>4</b>–<b>7</b>, <b>9</b>, <b>10</b>), aglycones (<b>11</b>–<b>13</b>), indole alkaloids (<b>14</b>, <b>15</b>, <b>17</b>), and jaspamide peptides (<b>18</b>–<b>22</b>) were also isolated. The structures of the three new compounds <b>1</b>–<b>3</b> were unambiguously elucidated based on NMR and mass spectroscopic data. Jaspnin A (<b>3</b>) contained a rare thiomethylated imidazolinium unit. Coupling an unbiased phenotypic assay using a human olfactory neurosphere-derived cell model of Parkinson’s disease to all of the natural products from the species <i>J. splendens</i> allowed the phenotypic profiles of the metabolites to be investigated

Tyrosyl-DNA Phosphodiesterase I Inhibitors from the Australian Plant <i>Macropteranthes leichhardtii</i>

Mass-directed isolation of the CH₂Cl₂/MeOH extract from the bark of an Australian plant, <i>Macropteranthes leichhardtii</i>, resulted in the purification of a new phenylpropanoid glucoside, macropteranthol (<b>1</b>), together with four known analogues (<b>2</b>–<b>5</b>). The structure of compound <b>1</b> was elucidated by NMR and MS data analyses and quantum chemical calculations. Compounds <b>3</b> and <b>5</b> showed inhibitory activity against tyrosyl-DNA phosphodiesterase I with IC₅₀ values of ∼1.0 μM

Aplysinellamides A–C, Bromotyrosine-Derived Metabolites from an Australian <i>Aplysinella</i> sp. Marine Sponge

Mass-directed fractionation of an extract from the Australian marine sponge <i>Aplysinella</i> sp., from the Great Barrier Reef, resulted in the isolation of four new bromotyrosine derivatives, aplysinellamides A–C (<b>1</b>–<b>3</b>) and aplysamine-1-<i>N</i>-oxide (<b>4</b>), along with six known compounds (<b>5</b>–<b>10</b>). The structure elucidation of compounds <b>1</b>–<b>4</b> was based on their 1D and 2D NMR and MS spectroscopic data. Aplysamine-1 (<b>6</b>) increased the apolipoprotein E secretion from human CCF-STTG1 astrocytoma cells by 2-fold at the concentration of 30 μM

Trikentramides A–D, Indole Alkaloids from the Australian Sponge <i>Trikentrion flabelliforme</i>

Chemical investigations of two specimens of <i>Trikentrion flabelliforme</i> collected from Australian waters have resulted in the identification of four new indole alkaloids, trikentramides A–D (<b>9</b>–<b>12</b>). The planar chemical structures for <b>9</b>–<b>12</b> were established following analysis of 1D/2D NMR and MS data. The relative configurations for <b>9</b>–<b>12</b> were determined following the comparison of ¹H NMR data with data previously reported for related natural products. The application of a quantum mechanical modeling method, density functional theory, confirmed the relative configurations and also validated the downfield carbon chemical shift observed for one of the quaternary carbons (C-5a) in the cyclopenta­[<i>g</i>]­indole series. The indole-2,3-dione motif present in trikentramides A–C is rare in nature, and this is the first report of these oxidized indole derivatives from a marine sponge

Ianthelliformisamines A–C, Antibacterial Bromotyrosine-Derived Metabolites from the Marine Sponge <i>Suberea ianthelliformis</i>

A high-throughput screening campaign using a prefractionated natural product library and an in vitro <i>Pseudomonas aeruginosa</i> (PAO200 strain) assay identified two antibacterial fractions derived from the marine sponge <i>Suberea ianthelliformis.</i> Mass-directed isolation of the CH₂Cl₂/CH₃OH extract from <i>S. ianthelliformis</i> resulted in the purification of three new bromotyrosine-derived metabolites, ianthelliformisamines A–C (<b>1</b>–<b>3</b>), together with the known natural products aplysamine 1 (<b>4</b>) and araplysillin I (<b>5</b>). The structures of <b>1</b>–<b>3</b> were determined following analysis of 1D and 2D NMR and MS spectroscopic data. This is the first report of chemistry from the marine sponge <i>S. ianthelliformis</i>. Ianthelliformisamine A (<b>1</b>) showed inhibitory activity against the Gram-negative bacterium <i>P. aeruginosa</i> with an IC₅₀ value of 6.8 μM (MIC = 35 μM)