Two novel triterpene holostane nonsulfated pentaosides, kolgaosides A (1) and B (2), and one known, holothurinoside B (3), were isolated from the Arctic sea cucumber Kolga hyalina, the second representative of the family Elpidiidae, order Elasipodida, from which triterpene glycosides have been obtained. The structures of 1 and 2 were elucidated using 1H and 13C NMR and 2D NMR procedures (HSQC, HMBC, COSY, ROESY, TOCSY) and HRESI mass-spectrometry. Kolgaosides A (1) and B (2) demonstrate low cytotoxic activity against the cells of the ascite form of mouse Ehrlich carcinoma and moderate hemolytic activity against mouse erythrocytes, despite the presence of hydroxy groups in the side chains of the aglycones. The glycosides of K. hyalina are similar to those of the Antarctic sea cucumber Rhipidothuria racowitzai H?rouard, 1901 (=Achlionice violaescupidata) (Elasipodida: Elpidiidae); this may have chemotaxonomic significance.
Kurilosides A1, A2, C1, D, E and F-Triterpene Glycosides from the Far Eastern Sea Cucumber Thyonidium (= Duasmodactyla) kurilensis (Levin): Structures with Unusual Non-Holostane Aglycones and Cytotoxicities.
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Pr. 100-letya Vladivostoka 159, 690022 Vladivostok, Russia.
Six new monosulfated triterpene tetra-, penta- and hexaosides, namely, the kurilosides A1 (1), A2 (2), C1 (3), D (4), E (5) and F (6), as well as the known earlier kuriloside A (7), having unusual non-holostane aglycones without lactone, have been isolated from the sea cucumber Thyonidium (= Duasmodactyla) kurilensis (Levin) (Cucumariidae, Dendrochirotida), collected in the Sea of Okhotsk near Onekotan Island from a depth of 100 m. Structures of the glycosides were established by 2D NMR spectroscopy and HR-ESI mass spectrometry. Kurilosides of the groups A and E contain carbohydrate moieties with a rare architecture (a pentasaccharide branched by C(4) Xyl1), differing from each other in the second monosaccharide residue (quinovose or glucose, correspondingly); kurilosides of the group C are characterized by a unique tetrasaccharide branched by a C(4) Xyl1 sugar chain; and kurilosides of the groups D and F are hexaosides differing from each other in the presence of an O-methyl group in the fourth (terminal) sugar unit. All these glycosides contain a sulfate group at C-6 of the glucose residue attached to C-4 Xyl1 and the non-holostane aglycones have a 9(11) double bond and lack ?-lactone. The cytotoxic activities of compounds 1-7 against mouse neuroblastoma Neuro 2a, normal epithelial JB-6 cells and erythrocytes were studied. Kuriloside A1 (1) was the most active compound in the series, demonstrating strong cytotoxicity against the erythrocytes and JB-6 cells and a moderate effect against Neuro 2a cells.
G. B. Elyakov Pacific Institute of Bioorganic Chemistry, The Far East Branch of the Russian Academy of Sciences , Prospect 100-let Vladivostoku 159, Vladivostok-22, Russia.
The first representatives of a new group of manzamine-related alkaloids with a previously unknown skeletal systems, namely, lissodendoric acids A (1) and B (2), were isolated from the sponge Lissodendoryx florida collected from the Sea of Okhotsk. The structures and absolute configurations have been elucidated by extensive spectroscopic analysis together with chemical transformations and quantum-chemical modeling. The lissodendoric acids show a potent capability to decrease the production of reactive oxygen species in neuroblastoma Neuro 2a and somewhat increase the survival of these cells upon treatment with 6-hydroxydopamine (an in vitro antiparkinson biotest).
The first representatives of a new group of manzamine-related alkaloids with a previously unknown skeletal systems, namely, lissodendoric acids A (1) and B (2), were isolated from the sponge Lissodendoryx florida collected from the Sea of Okhotsk. The structures and absolute configurations have been elucidated by extensive spectroscopic analysis together with chemical transformations and quantum-chemical modeling. The lissodendoric acids show a potent capability to decrease the production of reactive oxygen species in neuroblastoma Neuro 2a and somewhat increase the survival of these cells upon treatment with 6-hydroxydopamine (an in vitro antiparkinson biotest).
The minor cerebrosides from a Far-Eastern glass sponge Aulosaccus sp. were analyzed as constituents of some multi-component RP-HPLC fractions. The structures of eighteen new and one known cerebrosides were elucidated on the basis of NMR spectroscopy, mass spectrometry, optical rotation data and chemical transformations. These ß-D-glucopyranosyl-(1?1)-ceramides contain sphingoid bases N-acylated with straight-chain (2R)-2-hydroxy fatty acids, namely, (2S,3S,4R,11Z)-2-aminoeicos-11-ene-1,3,4-triol, acylated with 15E-22:1, 16Z-21:1, 15Z-21:1, 15Z-20:1, 15E-20:1, 19:0, 18:0 acids, (2S,3S,4R)-2-amino-13-methyltetradecane-1,3,4-triol--with 19Z-26:1, 16Z-23:1, 23:0, 22:0 acids, (2S,3S,4R)-2-amino-14-methylpentadecane-1,3,4-triol--with 16Z-23:1, 16E-23:1, 15Z-22:1, 22:0 acids, (2S,3S,4R)-2-amino-14-methylhexadecane-1,3,4-triol, linked to 16Z-23:1, 15Z-22:1 acids, (2S,3S,4R)-2-amino-9-methylhexadecane-1,3,4-triol--to 16Z-23:1 acid, and (2S,3S,4R)-2-aminohexadecane-1,3,4-triol, attached to 15Z-22:1 acid. The 13-methyl and 9-methyl-branched trihydroxy sphingoid base backbones (C15 and C17, respectively) have not been found previously in sphingolipids. The ceramide parts, containing other backbones, present new variants of N-acylation of the marine sphingoid bases with the 2-hydroxy fatty acids. The combination of the instrumental and chemical methods used in this study improved the efficiency of the structural analysis of such complex cerebroside mixtures that gave more detailed information on glycosphingolipid metabolism of the organism.
Structures and Bioactivities of Psolusosides B1, B2, J, K, L, M, N, O, P, and Q from the Sea Cucumber Psolus fabricii. The First Finding of Tetrasulfated Marine Low Molecular Weight Metabolites.
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Pr. 100-letya Vladivostoka 159, 690022 Vladivostok, Russia.
Ten new di-, tri- and tetrasulfated triterpene glycosides, psolusosides B1 (1), B2 (2), J (3), K (4), L (5), M (6), N (7), O (8), P (9), and Q (10), were isolated from the sea cucumber Psolus fabricii collected in the Sea of Okhotsk near the Kurile Islands. Structures of these glycosides were established by two-dimensional (2D) NMR spectroscopy and HR-ESI mass-spectrometry. It is particularly interesting that highly polar compounds 9 and 10 contain four sulfate groups in their carbohydrate moieties, including two sulfates in the same terminal glucose residue. Glycoside 2 has an unusual non-holostane aglycone with 18(16)-lactone and a unique 7,8-epoxy fragment. Cytotoxic activities of compounds 1-10 against several mouse cell lines such as Ehrlich ascites carcinoma cells, neuroblastoma Neuro 2A, normal epithelial JB-6 cells, and erythrocytes were quite different depending both on structural peculiarities of these glycosides and the type of cells subjected to their actions. Psolusoside L (5), pentaoside, with three sulfate groups at C-6 of two glucose and one 3-O-methylglucose residue and holostane aglycone, is the most active compound in the series. The presence of a sulfate group at C-2 of the terminal glucose residue attached to C-4 of the first (xylose) residue significantly decreases activities of the corresponding glycosides. Psolusosides of group B (1, 2, and known psolusoside B) are inactive in all tests due to the presence of non-holostane aglycones and tetrasaccharide-branched sugar chains sulfated by C-2 of Glc4.
Structures and Bioactivities of Six New Triterpene Glycosides, Psolusosides E, F, G, H, H1, and I and the Corrected Structure of Psolusoside B from the Sea Cucumber Psolus fabricii.
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Pr. 100-letya Vladivostoka 159, Vladivostok 690022, Russia. sialexandra@mail.ru.
Seven sulfated triterpene glycosides, psolusosides B (1), E (2), F (3), G (4), H (5), H1 (6), and I (7), along with earlier known psolusoside A and colochiroside D have been isolated from the sea cucumber Psolus fabricii collected in the Sea of Okhotsk. Herein, the structure of psolusoside B (1), elucidated by us in 1989 as a monosulfated tetraoside, has been revised with application of modern NMR and particularly MS data and proved to be a disulfated tetraoside. The structures of other glycosides were elucidated by 2D NMR spectroscopy and HR-ESI mass-spectrometry. Psolusosides E (2), F (3), and G (4) contain holostane aglycones identical to each other and differ in their sugar compositions and the quantity and position of sulfate groups in linear tetrasaccharide carbohydrate moieties. Psolusosides H (5) and H1 (6) are characterized by an unusual sulfated trisaccharide carbohydrate moiety with the glucose as the second sugar unit. Psolusoside I (7) has an unprecedented branched tetrasaccharide disulfated carbohydrate moiety with the xylose unit in the second position of the chain. The cytotoxic activities of the compounds 2-7 against several mouse cell lines-ascite form of Ehrlich carcinoma, neuroblastoma Neuro 2A, normal epithelial JB-6 cells, and erythrocytes-were quite different, at that hemolytic effects of the tested compounds were higher than their cytotoxicity against other cells, especially against the ascites of Ehrlich carcinoma. Interestingly, psolusoside G (4) was not cytotoxic against normal JB-6 cells but demonstrated high activity against Neuro 2A cells. The cytotoxic activity against human colorectal adenocarcinoma HT-29 cells and the influence on the colony formation and growth of HT-29 cells of compounds 1-3, 5-7 and psolusoside A was checked. The highest inhibitory activities were demonstrated by psolusosides E (2) and F (3).
