Nazumazoles A–C, Cyclic Pentapeptides Dimerized through a Disulfide Bond from the Marine Sponge <i>Theonella swinhoei</i>

A mixture of nazumazoles A–C (<b>1</b>–<b>3</b>) was purified from the extract of the marine sponge <i>Theonella swinhoei</i>. The mixture was eluted as an extraordinarily broad peak in the reversed-phase HPLC. The structures of nazumazoles were determined by interpretation of the NMR data and chemical degradations. Nazumazoles contain one residue each of alanine-derived oxazole and α-keto-β-amino acid residue. Nazumazoles exhibited cytotoxicity against P388 cells

Nazumazoles D–F, Cyclic Pentapeptides That Inhibit Chymotrypsin, from the Marine Sponge <i>Theonella swinhoei</i>

Nazumazoles D–F (<b>1</b>–<b>3</b>) were isolated from the marine sponge <i>Theonella swinhoei.</i> The compounds gave extremely broad peaks by reversed-phase HPLC using an ODS column. HPLC using a gel permeation column was instrumental for the separation of the three compounds. Their planar structures were determined by interpretation of NMR data to be cyclic pentapeptides. Nazumazoles D–F contained one residue each of α-keto-l-norvaline (l-Knv) {or α-keto-d-leucine (l-Kle)}, l-alanyloxazole (l-Aox), d-Abu (or d-Ser), <i>N</i>-α-CHO-β-l-Dpr, and <i>cis</i>-4-methyl-l-proline. The absolute configuration of each amino acid residue was determined by Marfey’s method in combination with conversion of the α-keto-β-amino acid to the α-amino acid by oxidation. Nazumazoles D–F are not cytotoxic against P388 cells at 50 μM, but inhibit chymotrypsin

Resolution of the Confusion in the Assignments of Configuration for the Ciliatamides, Acylated Dipeptides from Marine Sponges

Direct comparison of authentic ciliatamide A with four synthetic isomers (<b>1</b>–<b>4</b>) by means of NMR and chiral-phase HPLC revealed that ciliatamide A possesses the 12<i>R</i> (d-<i>N</i>-MePhe residue) and 22<i>S</i> (l-Lys residue) configurations, which were not identical with either our previous assignment or those proposed by others through total synthesis. The absolute configuration of the methionine sulfoxide residue in ciliatamide D was also revised to be d

Revised Structure of Cyclolithistide A, a Cyclic Depsipeptide from the Marine Sponge <i>Discodermia japonica</i>

A cyclic peptide was isolated from the deep-sea marine sponge <i>Discodermia japonica</i>, 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 Marfey’s 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

Miuramides A and B, Trisoxazole Macrolides from a <i>Mycale</i> sp. Marine Sponge That Induce a Protrusion Phenotype in Cultured Mammalian Cells

Morphology-guided cell-based screening of the extract of a <i>Mycale</i> sp. marine sponge led to the isolation of two trisoxazole macrolides, miuramides A (<b>1</b>) and B (<b>2</b>), which induced characteristic morphological changes in 3Y1 cells. The structure of <b>1</b> including absolute configuration was elucidated by a combination of the analysis of spectroscopic data, derivatization, and degradation. Both compounds exhibit potent cytotoxicity against 3Y1 cells

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

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

Isolation of Spirastrellolides A and B from a Marine Sponge <i>Epipolasis</i> sp. and Their Cytotoxic Activities

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

Enigmazole Phosphomacrolides from the Marine Sponge Cinachyrella enigmatica

Enigmazole B (1) and four new analogues, cis-enigmazole B (2), dehydroenigmazole B (3), enigmimide B (4), and enigmimide A (5), were isolated from the marine sponge Cinachyrella enigmatica. Their planar structures were elucidated by detailed NMR and MS data analyses, which established 1–3 to be oxazole-substituted 18-membered phosphomacrolides, while 4 and 5 were oxazole ring-opened congeners. The relative and absolute configurations in 1 were determined by a combination of chemical transformations and spectroscopic analyses. Photooxidation of the oxazole moiety in 1 gave enigmimide B (4), thus establishing that 4 has the same absolute configuration of 1. Enigmazole B (1) along with analogues 2 and 3 showed cytotoxicity against murine IC-2 mast cells with IC50 values of 3.6–7.0 μM. The enigmimides (4 and 5) and dephosphoenigmazoles did not show cytotoxicity (IC50 > 10 μM), implying that both the oxazole moiety and the phosphate group are necessary for the cytotoxicity of the enigmazole class macrolides

Cycloforskamide, a Cytotoxic Macrocyclic Peptide from the Sea Slug <i>Pleurobranchus forskalii</i>

A macrocylic dodecapeptide, cycloforskamide, was isolated from the sea slug <i>Pleurobranchus forskalii</i>, collected off Ishigaki Island, Japan. Its planar structure was deduced by extensive NMR analyses and was further confirmed by MS/MS fragmentation analyses. Finally, the absolute configuration was determined by total hydrolysis and chiral-phase gas chromatographic analysis. This novel dodecapeptide contains three d-amino acids and three thiazoline heterocycles and exhibits cytotoxicity against murine leukemia P388 cells, with an IC₅₀ of 5.8 μM

Gliotoxin Analogues from a Marine-Derived Fungus, <i>Penicillium</i> sp., and Their Cytotoxic and Histone Methyltransferase Inhibitory Activities

Seven gliotoxin-related compounds were isolated from the fungus <i>Penicillium</i> sp. strain JMF034, obtained from deep sea sediments of Suruga Bay, Japan. These included two new metabolites, bis­(dethio)-10a-methylthio-3a-deoxy-3,3a-didehydrogliotoxin (<b>1</b>) and 6-deoxy-5a,6-didehydrogliotoxin (<b>2</b>), and five known metabolites (<b>3</b>–<b>7</b>). The structures of the new compounds were elucidated by analysis of spectroscopic data and the application of the modified Mosher’s analysis. All of the compounds exhibited cytotoxic activity, whereas compounds containing a disulfide bond showed potent inhibitory activity against histone methyltransferase (HMT) G9a. None of them inhibited HMT SET7/9