黑乳海参和黄疣海参生物活性成分研究
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摘要
作为本研究中心“海洋天然活性成分研究和新药开发”这一研究方向的一个子课题,本文主要介绍了黑乳海参(Holothuria nobilis Selenka)和黄疣海参(Holothuria hilla Lesson)中皂苷类生物活性成分的研究。两种海参均为体形较大的海参,在我国从福建东山到海南岛的海域均有广泛分布。目前国内外尚未见有关该两种海参体内皂苷类成分的研究报道。在本课题的研究中,作者以稻瘟霉活性追踪为指导,应用大孔吸附树脂,硅胶,反相硅胶,葡聚糖凝胶等多种现代层析分离技术,对采集于我国福建省东山岛海域的黑乳海参及黄疣海参体内的抗肿瘤与抗真菌活性成分进行了系统的分离纯化和药理研究。共分离得到单体化合物19个。对活性较强,得量较多的化合物进行化学结构修饰,得到衍生物5个。应用现代光谱技术(尤其是2D-NMR和ESI-MS技术)和化学方法对这些化合物进行结构测定,确定了其中20个化合物的化学结构和立体构型。其中新化合物15个,包括皂苷类化合物13个,苷元2个。
从黑乳海参中分离纯化得到化合物12个,经过化学修饰得到化合物5个,测定所有17个化合物的化学结构。其中分离得到的10个新的皂苷化学结构为:3-O-{3''''-O-甲基-β-D-吡喃葡萄糖(1→3)-β-D-吡喃奎诺糖(1→)-β-D-吡喃奎诺糖(1→2)-4'-O-磺酸钠-β-D-吡喃木糖}-海参烷-9-烯-3β,12α,17α,25β-四醇,命名为nobiliside A(1):3-O-{3''''-O-甲基-β-D-吡喃葡萄糖(1→3)-β-D-吡喃葡萄糖(1→4)-β-D-吡喃奎诺糖(1→2)-4'-O-磺酸钠-β-D-吡喃木糖}-海参烷-22,25环氧-9-烯-3β,12α,17α,25β-四醇,命名为nobiliside B(2);3-O-{β-D-吡喃奎诺糖(1→2)-4'-O-磺酸钠-β-D-吡喃木糖}-海参烷-9-烯-18,16-内酯环-22,25-环氧-3β,12α,17α-三醇,命名为nobiliside C(3);3-O-{β-D-吡喃木糖(1→2)-4'-O-磺酸钠-β-D-吡喃木糖}-海参烷-9-烯-3β,12α,17α,25β-四醇,命名为nobiliside D(4);3-O-β-D-吡喃木糖-16β-乙酰氧基-海参烷-9-烯-22,25-环氧-3β,12α,17α-三醇,命名为nobiliside E(5);16β-乙酰氧基-3-O-[3''''-O-甲基-β-D-吡喃葡萄糖-(1→3)-β-D-吡喃木糖-(1→3)-β-D-吡喃奎诺糖-(1→2)-4'-O-磺酸钠-β-D-吡喃木糖]-海参烷-7,22-二烯-3β,17α-二醇,命名为nobiliside F(6);3-O-[β-D-吡喃葡萄糖-(1→3)-4'-O-磺酸钠-β-D-吡喃木糖]-海参烷-9-烯22,25-环氧-3β,17α-二醇,命名为nobiliside G(7);3-O-{β-D-吡喃奎诺糖(1→2)-4'-O-磺酸钠-β-D-吡喃木糖}-
Holothuria nobilis Selenka and Holothuria hilla Lesson, Holothuriidae-typesea cucumbers, are both widely distributed in the South China Sea, especially Dongshan Island, Fujian Province, People's Republic of China. Guided by P. oryzae bioassay model, the antitumor and antifungal constituents of these two kinds of sea cucumber have been investigated by various chromatography methods including LPLC, MPLC,HPLC on resin, silica gel, ODS RP C-18 and Zobax SB C-18 respectively, and twenty four compounds were isolated by various chromatography methods. On the basis of chemical and spectral analysis, especially by 2D-NMR and ESI-MS techniques, the structures oftwenty compounds were elucidated.The structures of ten new triterpene glycosides from the H. nobilis were elucidated as: 3-O-{3""-O-methyl-β-D-glucopyranosyl(1→3)-β-D-quinovopyrano syl(1→4)-β-D-quinovopyranosyl(1→2)-4'-O-sulfate-β-D-xylopyranosyl}-holosta-9 -en-3β,12α,17α,25β-tetraol sodium salt (nobiliside A); 3-O-{3""-O-methyl-β-D-glucopyranosyl(1→3)-β-D- glucopyranosyl(1→4)-β-D-quinovopyranosyl(1→2)-4' -O-sulfate-β-D-xylopyranosyl}-holosta-22,25-epoxy-9-ene-3β,12α, 17α,25β-tetraol-sodium salt (nobiliside B); 3-O-{β-D-quinovopyranosyl(1→2)-4'-O-sulfate-β-D-xylopyranosyl}-holoshillaside A8(16)-lactone-22,25-epoxy-9-ene-3β,12α,17α-triol sodium salt (nobiliside C); 3-O{β-D-xylopyranosyl(1→2)-4'-O-sulfate-β-D-xy lopyranosyl}-holosta-9-ene-3β,12α,17α,25β-tetraol sodium salt (nobiliside D); 1 6β-acetoxy-3-O-β-D-xylopyranosyl-holosta-22,25-epoxy-9-ene-3β,12α,17α-triol (nobiliside E); 16β-acetoxy-3-O-{3""-O-methyl-β-D-glucopyranosyl(1→3)-β-D-qu inovopyranosyl(1→4)-β-D-xylopyranosyl(1→2)-4'-O-sulfate-β-D-xylopyranosyl}-h olosta-7,22-diene-3β,17α-diol-sodium salt (nobiliside F); 3-O-{β-D-glucopyrano syl(1→2)-4'-O-sulfate-β-D-xylopyranosyl}-holosta-9-ene-22,25-epoxy-3β,17α-diol -sodium salt (nobiliside G); 3-O-{β-D-quinovopyranosyl(1→2)-4'-O-sulfateβ-D-xylopyranosyl}-holosta-22,25-epoxy-9-ene-3β,12α,17α-triol-sodium salt (nobilisi de H); 16β-acetoxy-3-O- (3""-O-methyl-β-D-glucopyranosyl(1→3)-β-D-glucopyra
从黑乳海参中分离纯化得到化合物12个,经过化学修饰得到化合物5个,测定所有17个化合物的化学结构。其中分离得到的10个新的皂苷化学结构为:3-O-{3''''-O-甲基-β-D-吡喃葡萄糖(1→3)-β-D-吡喃奎诺糖(1→)-β-D-吡喃奎诺糖(1→2)-4'-O-磺酸钠-β-D-吡喃木糖}-海参烷-9-烯-3β,12α,17α,25β-四醇,命名为nobiliside A(1):3-O-{3''''-O-甲基-β-D-吡喃葡萄糖(1→3)-β-D-吡喃葡萄糖(1→4)-β-D-吡喃奎诺糖(1→2)-4'-O-磺酸钠-β-D-吡喃木糖}-海参烷-22,25环氧-9-烯-3β,12α,17α,25β-四醇,命名为nobiliside B(2);3-O-{β-D-吡喃奎诺糖(1→2)-4'-O-磺酸钠-β-D-吡喃木糖}-海参烷-9-烯-18,16-内酯环-22,25-环氧-3β,12α,17α-三醇,命名为nobiliside C(3);3-O-{β-D-吡喃木糖(1→2)-4'-O-磺酸钠-β-D-吡喃木糖}-海参烷-9-烯-3β,12α,17α,25β-四醇,命名为nobiliside D(4);3-O-β-D-吡喃木糖-16β-乙酰氧基-海参烷-9-烯-22,25-环氧-3β,12α,17α-三醇,命名为nobiliside E(5);16β-乙酰氧基-3-O-[3''''-O-甲基-β-D-吡喃葡萄糖-(1→3)-β-D-吡喃木糖-(1→3)-β-D-吡喃奎诺糖-(1→2)-4'-O-磺酸钠-β-D-吡喃木糖]-海参烷-7,22-二烯-3β,17α-二醇,命名为nobiliside F(6);3-O-[β-D-吡喃葡萄糖-(1→3)-4'-O-磺酸钠-β-D-吡喃木糖]-海参烷-9-烯22,25-环氧-3β,17α-二醇,命名为nobiliside G(7);3-O-{β-D-吡喃奎诺糖(1→2)-4'-O-磺酸钠-β-D-吡喃木糖}-
Holothuria nobilis Selenka and Holothuria hilla Lesson, Holothuriidae-typesea cucumbers, are both widely distributed in the South China Sea, especially Dongshan Island, Fujian Province, People's Republic of China. Guided by P. oryzae bioassay model, the antitumor and antifungal constituents of these two kinds of sea cucumber have been investigated by various chromatography methods including LPLC, MPLC,HPLC on resin, silica gel, ODS RP C-18 and Zobax SB C-18 respectively, and twenty four compounds were isolated by various chromatography methods. On the basis of chemical and spectral analysis, especially by 2D-NMR and ESI-MS techniques, the structures oftwenty compounds were elucidated.The structures of ten new triterpene glycosides from the H. nobilis were elucidated as: 3-O-{3""-O-methyl-β-D-glucopyranosyl(1→3)-β-D-quinovopyrano syl(1→4)-β-D-quinovopyranosyl(1→2)-4'-O-sulfate-β-D-xylopyranosyl}-holosta-9 -en-3β,12α,17α,25β-tetraol sodium salt (nobiliside A); 3-O-{3""-O-methyl-β-D-glucopyranosyl(1→3)-β-D- glucopyranosyl(1→4)-β-D-quinovopyranosyl(1→2)-4' -O-sulfate-β-D-xylopyranosyl}-holosta-22,25-epoxy-9-ene-3β,12α, 17α,25β-tetraol-sodium salt (nobiliside B); 3-O-{β-D-quinovopyranosyl(1→2)-4'-O-sulfate-β-D-xylopyranosyl}-holoshillaside A8(16)-lactone-22,25-epoxy-9-ene-3β,12α,17α-triol sodium salt (nobiliside C); 3-O{β-D-xylopyranosyl(1→2)-4'-O-sulfate-β-D-xy lopyranosyl}-holosta-9-ene-3β,12α,17α,25β-tetraol sodium salt (nobiliside D); 1 6β-acetoxy-3-O-β-D-xylopyranosyl-holosta-22,25-epoxy-9-ene-3β,12α,17α-triol (nobiliside E); 16β-acetoxy-3-O-{3""-O-methyl-β-D-glucopyranosyl(1→3)-β-D-qu inovopyranosyl(1→4)-β-D-xylopyranosyl(1→2)-4'-O-sulfate-β-D-xylopyranosyl}-h olosta-7,22-diene-3β,17α-diol-sodium salt (nobiliside F); 3-O-{β-D-glucopyrano syl(1→2)-4'-O-sulfate-β-D-xylopyranosyl}-holosta-9-ene-22,25-epoxy-3β,17α-diol -sodium salt (nobiliside G); 3-O-{β-D-quinovopyranosyl(1→2)-4'-O-sulfateβ-D-xylopyranosyl}-holosta-22,25-epoxy-9-ene-3β,12α,17α-triol-sodium salt (nobilisi de H); 16β-acetoxy-3-O- (3""-O-methyl-β-D-glucopyranosyl(1→3)-β-D-glucopyra
引文
(1) 廖玉麟编著:《中国动物志棘皮动物门海参纲》,北京:科学出版社,1997年版.
(2) Kitagawa I.; Yamanaka H.; Kobayashi M.; et al. Saponin and Sapogenol. ⅩⅩⅦ. Revised structures of holotoxin A and B, two antifungal oligoglycosides from the sea cucumber Stichopus japonicus SELENKA. Chem. Pharm. Bull. 1978, 26(12): 3722-3731.
(3) Maltsev I.I.; Stonik V.A.;Kalinovsky A.I. et al. Triterpene glycosides from sea cucumber Stichopus japonicus SELENKA. Comp. Biochem. Physiol. 1984,78B(2):421-426.
(4) Avilov S. A.; Stonik V.A. New triterpene glycosides from the holothurian. Chem. Nat. Comp. 1988,24:656.
(5) Kalinin V.I.; Stepanov B. R.; Stonik V. A.; et al. Structure of psolusoside A-a holostane triterpene glycoside. Chem. Nat. Comp. 1985,21:212.
(6) Miyamoto T.; Togawa K.; Higuchi R.; et al. Six newly identified biologically active triterpenoid glycoside sulfates from the sea cucumber Cucumaria echinata. Liebigs. Ann. Chem. 1990: 453-460.
(7) Chludil H.D.; Muniain C. C.; Seldes A.M.; et al. Cytotoxic and antifungal triterpene glycosides from the Patagonian sea cucumber Hemoiedema spectabilis. J. Nat. Prod. 2002,65:860-865.
(8) Drozdova O. A.; Avilov S. A.; Kalinin V.I. et al. Cytotoxic triterpene glycosides from the far-eastern sea cucumber belonging to the genus Cucumaria. Liebigs. Ann. Chem. 1997:2351-2356.
(9) Miyamoto T.; Togawa K.; Higuchi R.; et al. Structures of four new triterpenoid oligoglycosides DS-penaustrosides A,B,C,and D from the sea cucumber Pentacta australis. J. Nat.Prod. 1992,55(7):940-946.
(10) Findaly J. A.; Yayli N. Novel sulfated oligosaccharides from the sea cucumber Cucumaria frondosa. J. Nat. Prod. 1992,55 (1):93-101.
(11) Yayli N.; Findaly J. A. A triterpenoid saponin from Cucumaria frondosa. Phytochemistry. 1999(50): 135-138.
(12) Kalinin V.I.; Avilov S.A.; Kalinina E.Y. Structure of eximisoside A, a novel triterpene glycoside from the far-eastern sea cucumber Psolus eximius, J.Nat.Prod. 1997,60:817-819.
(13) Maier M.S.; Roccatagliata A.J.; Kuriss A. et al.Two new cytotoxic and virucidal trisulfated triterpene glycosides from the antarctic sea cucumber Staurocucumis liouvillei, J. Nat. Prod. 2001,64:732-736.
(14) Zou Z.R.; Yi Y.H.; Wu J.H.; et al. Intercedensides A-C, three new cytotoxic triterpene glycosides from the sea cucumber Mensamaria intercedens Lampert. J. Nat. Prod. 2003,66:1055-1060.
(15) Kitagawa I.; Kobayashi M.; Hori M. et al. Structures of four new triterpenoidal oligoglycosides, bivittoside A,B,C,and D,from the sea cucumber Bohadschia bivittata MITSUKURI. Chem.Pharm.Bull. 1981,29(1):282-285.
(16) Kitagawa I.; Kobayashi M.; Hori M. et al. Marine natural products. ⅩⅧ. Four lanostane type triterpene oligoglycosides, bivittosides A,B,C,and D,from the Okinawan sea cucumber Bohadschia bivittata MITSUKURI. Chem.Pharm.Bull. 1989,37(1):61-67.
(17) Kitagawa I.; Inamoto T.; Fuchida M. et al. Structures of echinoside A and B,two antifugal oligoglycosides from the sea cucumber Actinopyga echinites (JAEGER). Chem. Pharm. Bull. 1980,28(5): 1651-1653.
(18) Kitagawa I.; Kobayashi M.; Inamoto T. et al. Marine natural products. ⅪⅤ. Structures of echinosides A and B, antifugal lanostane-oligosides from sea cucumber Actinopyga echinites (JAEGER). Chem. Pharm. Bull. 1985,33(12):5214-5224.
(19) Kitagawa I.; Kobayashi M.; Inamoto T. et al. The structures of six antifugal oligoglycosides, stichlorosides A_1,A_2,B_1,B_2,C_1, and C_2,, from the sea cucumber Stichopus chloronotus (BRANDT). Chem.Pharm.Bull. 1981,29(8):2387-2391.
(20) Kitagawa I.; Nishino T.; Kobayashi M. et al. Marine natural products. Ⅶ. Bioactive triterpene-oligoglycosides from the sea cucumber Holothuria leucospilota BRANDT (1). Structure of holothurin B. Chem. Pharm. Bull. 1981,29(7):1942-1950.
(21) Kitagawa I.; Nishino T.; Kobayashi M. et al. Marine natural products. Ⅷ. Bioactive triterpene-oligoglycosides from the sea cucumber Holothuria leucospilota BRANDT (2). Structure of holothurin A. Chem. Pharm. Bull. 1981, 29(7): 1951-1956.
(22) Kitagawa I.; Kobayashi M.; Kyogoku Y. et al. Marine natural products. Ⅸ. Structural elucidation of triterpenoidal oligoglycosides from the Bahamean sea cucumber Actinopyga agassizi SELENKA. Chem.Pharm.Bull. 1982,30(5):2045-2050.
(23) Encarnacion R.; Carrasco G.; Espinoza M. et al. Neothyoside A, proposed structure of a triterpenoid tetraglycoside from the Pacific sea cucumber, Neothyone gibbosa. J. Nat. Prod. 1989,52(2):248-251.
(24) Kitagawa I.; Kobayashi M.; Son B.W. et al. Marine natural products. ⅪⅩ. Pervicosides A, B, and C, lanostane-type triterpene-oligoglycoside sulfates from the sea cucumber Holothuria pervicax. Chem. Pharm. Bull. 1989, 37(5): 1230-1234.
(25) Rodriguez J.; Castro R.; Riguera R. et al. Holothurinosides: new antitumour non sulphated triterpenoid glycosides from the sea cucumber Holothuria forskalii. Tetrahedron. 1991, 47(26): 4753-4762.
(26) Avilov S. A.; Kalinin V.I.; Makarieva T.N. et al. Structure of cucumarioside G2, a novel nonholostane glycoside from the sea cucumber Eupentacta fraudatrix. J. Nat. Prod. 1994, 57(8):1166-1171.
(27) Avilov S.A.; Antonov A.S.; Drozdova O.A. et al. Triterpene glycosides from the far-eastern sea cucumber Pentamera calcigera. 1. Monosulfated glycosides and cytotoxicity of their unsulfated derivatives. J. Nat. Prod. 2000,63:65-71.
(28) Hegde V.R.; Chan T.M.; Pu H.Y. Two selective novel triterpene glycosides from sea cucumber Telenata ananas: inhibitors of chemokine receptor-5. Bioorg. Med Chem. Lett. 2002,12:3203-3205.
(29) Kalinin V.I. Kalinovskii A.I. Stonik V.A. et al. Structure of psolusoside B-a nonholostane triterpene glycoside. Chem. Nat. Comp. 1989,25:311-317.
(30) Avilov S.A.; Kalinovsky A.I.; Kalinin V.I. Koreoside A, a new nonholostane triterpene glycoside from the sea cucumber Cucumaria koraiensis. J. Nat. Prod. 1997,60:808-810.
(31) Avilov S.A.; Antonov A.S.; Silchenko A. S. et al. Triterpene glycosides from the far eastern sea cucumber cucumaria conicospermium. J. Nat. Prod. 2003,66:910-916.
(32) Anisimov M. M.; Prokofieva N.G.; Korotkikh L.Y. et al. Comparative study of cytototic activity of triterpene glycosides from marine organisms. Toxicon. 1980,20(1): 221～223.
(33) 周清凯,杨惠英,蔡云见,等.玉足海参素的抗真菌作用及其临床应用.海洋药物,1985,(4):43～44.
(34) Kunetsova T.A.; Anisimov M.M.; Popov A.M.; et al. A comparative study in vitro of physiological activity of triterpene glycosides of marine invertebrates of echinoderm type. Comp. Biochem. Physiol. 1982, 73 (1): 41～43.
(35) Kalinin V.I.; Prokofieva N.G.; Likhatskaya G.N.; et al. Hemolytic activities of triterpene glycosides from the holothurian order Dendrochirotida: some trends in the evolution of this group of toxins. Toxicon. 1996, 34(2): 475-478.
(36) Gorshkova I.A.; Kalinovsky A.I.; Ilyin S.G. Physicochemical characteristics of interaction of toxic triterpene glycosides from holothrians with rat brain Na+-K+-ATPase. Toxicon. 1989,27(8):937-945.
(37) Gorshkov B.A.; Gorshkova I.A.; Stonik V.A. Effect of marine glycosides on adenosinetriphosphatase activity. Toxicon. 1982,20(3):655-658.
(38) Santhakumari G.; Stephen J. Antimitotic effects of holothurin. Cytologia. 1998, 53(2): 163～168.
(39) Turishchev S.N.; Bol'shakova G. V.; Sakandelidze O.G. The effect of triterpene glycoside complexes from holothurians on liver repair. Izv. Akad. Nauk. SSSR. Biol. 1991 Mar-Apr(2): 306-310.
(40) Kobayashi H, Namikoshi M, Yoshimoto T, et. al, A screening method for antimiotic and antifungal substances using conidia of Pyricularia oryzae, modification and application to tropical marine fungi[J]. J Antibiotics, 1996, 49(9): 873～879.
(41) 于德泉,杨峻山主编.分析化学手册(第二版)第七分册 核磁共振波谱分析.北京:化学工业出版社,1999:495.
(42) 劳彦斌,蒋亭,李军,付宏征,林文翰 柄海鞘Styela clava次生代谢产物的化学研究(Ⅰ) 中国海洋药物.2001,20(2):14。
(2) Kitagawa I.; Yamanaka H.; Kobayashi M.; et al. Saponin and Sapogenol. ⅩⅩⅦ. Revised structures of holotoxin A and B, two antifungal oligoglycosides from the sea cucumber Stichopus japonicus SELENKA. Chem. Pharm. Bull. 1978, 26(12): 3722-3731.
(3) Maltsev I.I.; Stonik V.A.;Kalinovsky A.I. et al. Triterpene glycosides from sea cucumber Stichopus japonicus SELENKA. Comp. Biochem. Physiol. 1984,78B(2):421-426.
(4) Avilov S. A.; Stonik V.A. New triterpene glycosides from the holothurian. Chem. Nat. Comp. 1988,24:656.
(5) Kalinin V.I.; Stepanov B. R.; Stonik V. A.; et al. Structure of psolusoside A-a holostane triterpene glycoside. Chem. Nat. Comp. 1985,21:212.
(6) Miyamoto T.; Togawa K.; Higuchi R.; et al. Six newly identified biologically active triterpenoid glycoside sulfates from the sea cucumber Cucumaria echinata. Liebigs. Ann. Chem. 1990: 453-460.
(7) Chludil H.D.; Muniain C. C.; Seldes A.M.; et al. Cytotoxic and antifungal triterpene glycosides from the Patagonian sea cucumber Hemoiedema spectabilis. J. Nat. Prod. 2002,65:860-865.
(8) Drozdova O. A.; Avilov S. A.; Kalinin V.I. et al. Cytotoxic triterpene glycosides from the far-eastern sea cucumber belonging to the genus Cucumaria. Liebigs. Ann. Chem. 1997:2351-2356.
(9) Miyamoto T.; Togawa K.; Higuchi R.; et al. Structures of four new triterpenoid oligoglycosides DS-penaustrosides A,B,C,and D from the sea cucumber Pentacta australis. J. Nat.Prod. 1992,55(7):940-946.
(10) Findaly J. A.; Yayli N. Novel sulfated oligosaccharides from the sea cucumber Cucumaria frondosa. J. Nat. Prod. 1992,55 (1):93-101.
(11) Yayli N.; Findaly J. A. A triterpenoid saponin from Cucumaria frondosa. Phytochemistry. 1999(50): 135-138.
(12) Kalinin V.I.; Avilov S.A.; Kalinina E.Y. Structure of eximisoside A, a novel triterpene glycoside from the far-eastern sea cucumber Psolus eximius, J.Nat.Prod. 1997,60:817-819.
(13) Maier M.S.; Roccatagliata A.J.; Kuriss A. et al.Two new cytotoxic and virucidal trisulfated triterpene glycosides from the antarctic sea cucumber Staurocucumis liouvillei, J. Nat. Prod. 2001,64:732-736.
(14) Zou Z.R.; Yi Y.H.; Wu J.H.; et al. Intercedensides A-C, three new cytotoxic triterpene glycosides from the sea cucumber Mensamaria intercedens Lampert. J. Nat. Prod. 2003,66:1055-1060.
(15) Kitagawa I.; Kobayashi M.; Hori M. et al. Structures of four new triterpenoidal oligoglycosides, bivittoside A,B,C,and D,from the sea cucumber Bohadschia bivittata MITSUKURI. Chem.Pharm.Bull. 1981,29(1):282-285.
(16) Kitagawa I.; Kobayashi M.; Hori M. et al. Marine natural products. ⅩⅧ. Four lanostane type triterpene oligoglycosides, bivittosides A,B,C,and D,from the Okinawan sea cucumber Bohadschia bivittata MITSUKURI. Chem.Pharm.Bull. 1989,37(1):61-67.
(17) Kitagawa I.; Inamoto T.; Fuchida M. et al. Structures of echinoside A and B,two antifugal oligoglycosides from the sea cucumber Actinopyga echinites (JAEGER). Chem. Pharm. Bull. 1980,28(5): 1651-1653.
(18) Kitagawa I.; Kobayashi M.; Inamoto T. et al. Marine natural products. ⅪⅤ. Structures of echinosides A and B, antifugal lanostane-oligosides from sea cucumber Actinopyga echinites (JAEGER). Chem. Pharm. Bull. 1985,33(12):5214-5224.
(19) Kitagawa I.; Kobayashi M.; Inamoto T. et al. The structures of six antifugal oligoglycosides, stichlorosides A_1,A_2,B_1,B_2,C_1, and C_2,, from the sea cucumber Stichopus chloronotus (BRANDT). Chem.Pharm.Bull. 1981,29(8):2387-2391.
(20) Kitagawa I.; Nishino T.; Kobayashi M. et al. Marine natural products. Ⅶ. Bioactive triterpene-oligoglycosides from the sea cucumber Holothuria leucospilota BRANDT (1). Structure of holothurin B. Chem. Pharm. Bull. 1981,29(7):1942-1950.
(21) Kitagawa I.; Nishino T.; Kobayashi M. et al. Marine natural products. Ⅷ. Bioactive triterpene-oligoglycosides from the sea cucumber Holothuria leucospilota BRANDT (2). Structure of holothurin A. Chem. Pharm. Bull. 1981, 29(7): 1951-1956.
(22) Kitagawa I.; Kobayashi M.; Kyogoku Y. et al. Marine natural products. Ⅸ. Structural elucidation of triterpenoidal oligoglycosides from the Bahamean sea cucumber Actinopyga agassizi SELENKA. Chem.Pharm.Bull. 1982,30(5):2045-2050.
(23) Encarnacion R.; Carrasco G.; Espinoza M. et al. Neothyoside A, proposed structure of a triterpenoid tetraglycoside from the Pacific sea cucumber, Neothyone gibbosa. J. Nat. Prod. 1989,52(2):248-251.
(24) Kitagawa I.; Kobayashi M.; Son B.W. et al. Marine natural products. ⅪⅩ. Pervicosides A, B, and C, lanostane-type triterpene-oligoglycoside sulfates from the sea cucumber Holothuria pervicax. Chem. Pharm. Bull. 1989, 37(5): 1230-1234.
(25) Rodriguez J.; Castro R.; Riguera R. et al. Holothurinosides: new antitumour non sulphated triterpenoid glycosides from the sea cucumber Holothuria forskalii. Tetrahedron. 1991, 47(26): 4753-4762.
(26) Avilov S. A.; Kalinin V.I.; Makarieva T.N. et al. Structure of cucumarioside G2, a novel nonholostane glycoside from the sea cucumber Eupentacta fraudatrix. J. Nat. Prod. 1994, 57(8):1166-1171.
(27) Avilov S.A.; Antonov A.S.; Drozdova O.A. et al. Triterpene glycosides from the far-eastern sea cucumber Pentamera calcigera. 1. Monosulfated glycosides and cytotoxicity of their unsulfated derivatives. J. Nat. Prod. 2000,63:65-71.
(28) Hegde V.R.; Chan T.M.; Pu H.Y. Two selective novel triterpene glycosides from sea cucumber Telenata ananas: inhibitors of chemokine receptor-5. Bioorg. Med Chem. Lett. 2002,12:3203-3205.
(29) Kalinin V.I. Kalinovskii A.I. Stonik V.A. et al. Structure of psolusoside B-a nonholostane triterpene glycoside. Chem. Nat. Comp. 1989,25:311-317.
(30) Avilov S.A.; Kalinovsky A.I.; Kalinin V.I. Koreoside A, a new nonholostane triterpene glycoside from the sea cucumber Cucumaria koraiensis. J. Nat. Prod. 1997,60:808-810.
(31) Avilov S.A.; Antonov A.S.; Silchenko A. S. et al. Triterpene glycosides from the far eastern sea cucumber cucumaria conicospermium. J. Nat. Prod. 2003,66:910-916.
(32) Anisimov M. M.; Prokofieva N.G.; Korotkikh L.Y. et al. Comparative study of cytototic activity of triterpene glycosides from marine organisms. Toxicon. 1980,20(1): 221～223.
(33) 周清凯,杨惠英,蔡云见,等.玉足海参素的抗真菌作用及其临床应用.海洋药物,1985,(4):43～44.
(34) Kunetsova T.A.; Anisimov M.M.; Popov A.M.; et al. A comparative study in vitro of physiological activity of triterpene glycosides of marine invertebrates of echinoderm type. Comp. Biochem. Physiol. 1982, 73 (1): 41～43.
(35) Kalinin V.I.; Prokofieva N.G.; Likhatskaya G.N.; et al. Hemolytic activities of triterpene glycosides from the holothurian order Dendrochirotida: some trends in the evolution of this group of toxins. Toxicon. 1996, 34(2): 475-478.
(36) Gorshkova I.A.; Kalinovsky A.I.; Ilyin S.G. Physicochemical characteristics of interaction of toxic triterpene glycosides from holothrians with rat brain Na+-K+-ATPase. Toxicon. 1989,27(8):937-945.
(37) Gorshkov B.A.; Gorshkova I.A.; Stonik V.A. Effect of marine glycosides on adenosinetriphosphatase activity. Toxicon. 1982,20(3):655-658.
(38) Santhakumari G.; Stephen J. Antimitotic effects of holothurin. Cytologia. 1998, 53(2): 163～168.
(39) Turishchev S.N.; Bol'shakova G. V.; Sakandelidze O.G. The effect of triterpene glycoside complexes from holothurians on liver repair. Izv. Akad. Nauk. SSSR. Biol. 1991 Mar-Apr(2): 306-310.
(40) Kobayashi H, Namikoshi M, Yoshimoto T, et. al, A screening method for antimiotic and antifungal substances using conidia of Pyricularia oryzae, modification and application to tropical marine fungi[J]. J Antibiotics, 1996, 49(9): 873～879.
(41) 于德泉,杨峻山主编.分析化学手册(第二版)第七分册 核磁共振波谱分析.北京:化学工业出版社,1999:495.
(42) 劳彦斌,蒋亭,李军,付宏征,林文翰 柄海鞘Styela clava次生代谢产物的化学研究(Ⅰ) 中国海洋药物.2001,20(2):14。