Yuji Ise

Calyxamides A and B, Cytotoxic Cyclic Peptides from the Marine Sponge Discodermia calyx

Cyclic peptides containing 5-hydroxytryptophan and thiazole moieties were isolated from the marine sponge Discodermia calyx collected near Shikine-jima Island, Japan. The structures of calyxamides A (1) and B (2), including the absolute configurations of all amino acids, were elucidated by spectroscopic analyses and degradation experiments. The structures are similar to keramamides F and G, previously isolated from Theonella sp. The analysis of the 16S rDNA sequences obtained from the metagenomic DNA of D. calyx revealed the presence of Candidatus Entotheonella sp., an unculturable δ-proteobacterium inhabiting the Theonella genus and implicated in the biosynthesis of bioactive peptides.

Isolation of spirastrellolides A and B from a marine sponge Epipolasis sp. and their cytotoxic activities.

Spirastrellolides A (1) and B (3) have been isolated as free acids from a marine sponge Epipolasis sp. collected in the East China Sea. These compounds had been isolated from the Caribbean marine sponge Spirastrella coccinea after conversion to the methyl ester. We examined the cytotoxic activities of 1 and 3 and found that the activities of the free acids are comparable to those of the corresponding methyl esters.

(―)-Duryne and Its Homologues, Cytotoxic Acetylenes from a Marine Sponge Petrosia sp.

Six linear acetylenes, (-)-duryne (1) and (-)-durynes B-F (2-6), were isolated from the marine sponge Petrosia sp. Their structures were elucidated by NMR and tandem FABMS analyses. The positions of the olefinic bonds were confirmed by ozonolysis experiments, and the absolute configurations were determined by the modified Moshers method. Compound 1 was found to be the enantiomer of duryne, a previously reported sponge metabolite. Compounds 1-6 show cytotoxicity against HeLa cells with IC50 values between 0.08 and 0.50 μM.

Revised Structure of Cyclolithistide A, a Cyclic Depsipeptide from the Marine Sponge Discodermia japonica

A cyclic peptide was isolated from the deep-sea marine sponge Discodermia japonica, and its NMR spectroscopic data were identical to those reported for cyclolithistide A, a known antifungal depsipeptide. However, the interresidue HMBC correlations suggested that the amino acid sequence was different from that of the original structure. Moreover, chiral-phase GC-MS, combined with Marfeys analysis, indicated that the absolute configurations of three amino acids were also antipodal. Here, we propose the revised structure of cyclolithistide A and address the configuration of the previously unassigned 4-amino-3,5-dihydroxyhexanoic acid (Adha) moiety.

Jasisoquinolines A and B, Architecturally New Isoquinolines, from a Marine Sponge Jaspis sp.

Two architecturally new isoquinolines, jasisoquinolines A and B, were isolated from a marine sponge Jaspis sp. as cathepsin B inhibitors. Their structures were determined by a combination of spectroscopic analyses and chemical methods. Both jasisoquinolines A and B inhibit cathepsin B with an IC(50) value of 10 μg/mL.

Cytotoxic Glycosylated Fatty Acid Amides from a Stelletta sp. Marine Sponge

We have discovered new glycosylated fatty acid amides, stellettosides, from a Stelletta sp. marine sponge. They were detected through LC-MS analysis of the extract combined with the cytotoxicity assay of the prefractionated sample. Their planar structures were determined by analyses of the NMR and tandem FABMS data. Stellettosides A1 and A2 (1 and 2) as well as stellettosides B1-B4 (3-6) were obtained as inseparable mixtures. Careful analysis of the NMR and tandem FABMS data of each mixture, along with comparison of the tandem FABMS data with that of a synthetic model compound, permitted us to assign the structure of the constituents in the mixture. The absolute configuration of the monosaccharide unit was determined by LC-MS after chiral derivatization. The relative configurations of the vicinal oxygenated methines in the fatty acid chains were assigned by the (1)H NMR data of the isopropylidene derivative. The mixture of stellettosides B1-B4 (3-6) exhibit moderate cytotoxic activity against HeLa cells with an IC50 value of 9 μM, whereas the mixture of stellettosides A1 and A2 (1 and 2) was not active at a concentration of 10 μM.

Isolation of Ciliatamide D from a Marine Sponge Stelletta sp. and a Reinvestigation of the Configuration of Ciliatamide A

A new lipopeptide, ciliatamide D (1), was isolated from a marine sponge Stelletta sp., collected at Oshimashinsone, together with the known compound ciliatamide A (2). Ciliatamide D (1) is a congener of 2, in which N-Me-Phe is replaced by N-Me-Met(O). Marfeys analysis of the acid hydrolysate of 1 demonstrated that the two constituent amino acids were both in the l-form. This result prompted us to carefully investigate the configuration of 2, resulting in the assignment of the l-form for both residues.

Structure Revision of Poecillastrin C and the Absolute Configuration of the β-Hydroxyaspartic Acid Residue

The planar structure of poecillastrin C (1) was revised through selective reduction of the ester carbon. The absolute configuration of the β-hydroxyaspartic acid (OHAsp) residue was determined to be d-threo by Marfeys analysis. The acid hydrolysate of the reduction product of 1 liberated (2R,3R)-2-amino-3,4-dihydroxybutanoic acid, demonstrating that the β-carboxyl group in poecillastrin C was esterified. The structures of poecillastrins B-D and 73-deoxychondropsin A were also revised.

Yakushinamides, Polyoxygenated Fatty Acid Amides That Inhibit HDACs and SIRTs, from the Marine Sponge Theonella swinhoei

Yakushinamides A (1) and B (2), prolyl amides of polyoxygenated fatty acids, have been isolated from the marine sponge Theonella swinhoei as inhibitors of HDACs and SIRTs. Their planar structures were determined by interpretation of the NMR data of the intact molecules and tandem FABMS data of the methanolysis products. For the assignment of the relative configurations of the three contiguous oxymethine carbons in 1 and 2, Kishis universal NMR database was applied to the methanolysis products. During the assignments of relative configurations of the isolated 1-hydroxy-3-methyl moiety in 1 and the isolated 1-hydroxy-2-methyl moiety in 2, we found diagnostic NMR features to distinguish each pair of diastereomers. The absolute configurations of 1 and 2 were determined by a combination of the modified Moshers method and Marfeys method. Although the modified Moshers method was successfully applied to the methanolysis product of 1, this method gave an ambiguous result at C-20 when applied to the methanolysis product of 2, even after oxidative cleavage of the C-14 and C-15 bond.