摘要
海绵是结构简单的低等动物，机体由多细胞组成，但细胞间仅有功能上的差异，还未形成组织或器官。海绵体内存在一种高效的过滤管系统，大量海水连同各种营养物质从中通过，经过滤后在各个功能细胞区被消化，进而为海绵的生长和繁殖提供养料和氧气。所以海绵可以在营养贫瘠的环境中生长，而且大多数海绵中有微生物与其共生。
海绵广泛分布于海洋中，从热带海域到温带海域甚至极地海域都发现有海绵存在。海绵通常能够产生大量的活性次生代谢产物用于防止腐生生物的危害，这一特点也使海绵在与其它生物的竞争中处于优势地位，而人类则把海绵作为活性新药先导化合物的来源。
运用正相硅胶柱、凝胶Sephadex LH-20柱以及高效液相等多种层析技术，对采自我国海南陵水海域的三种海绵进行了较深入的化学成分的研究，从中共分离鉴定了51个化合物，包括24个倍半萜、22个二倍半萜、1个三萜、3个吲哚类化合物和1个甾醇。通过综合波谱分析技术鉴定了上述化合物的结构，51个化合物中有10个新化合物，它们是二倍半萜hyrtiosin A-E；吲哚生物碱hyrtioindolealkaloid；螺环倍半萜spirofragilin；含甲酰胺基团的倍半萜acanformamide：含异硫腈基团的倍半萜acanisothiocynate和acanisothiobisabolene。另外还有3个化合物第一次从自然界分离得到。己知化合物中有18个是首次从我国南海海绵中分离得到。还发现新螺环倍半萜spirofragilin在氘代氯仿(CDCl_3)中室温下会发生化学变化，生成二聚体，并且通过单晶X-衍射分析确定了二聚体的结构。
通过广泛的生物活性筛选，发现化合物204(heteronemin)对人肺癌A-549、人白血病HL-60、人宫颈癌HELA和人肝癌BEL-7402等四个细胞株的增殖有抑制作用，IC_(50)分别为2.31×10~(-10)M，1.92×10~(-7)M，2.42×10~(-6)M和1.72×10~(-8)M。还发现化合物222(hyrtiosal)、208(12，18-diepiscalaradial)、212(scalarafuran)具有PTP1B酶抑制作用，IC_(50)分别为6.04×10~(-5)M，3.16×10~(-5)M和5.42×10~(-5)M。
The marine sponges are considered to be primitive organisms, with relative simple internal organization. The constituent cells of marine sponges form neither tissue layer nor organs, however, it dose perform specialized functions depending on the location within the sponge. Marine sponges have a very strong pumping capability of filtering a large volume of water through its tissues for food and oxygen, it is thus not surprising that marine sponges can live in a poor nutrient environment and many marine sponges contain symbiotic micro-organisms. Marine sponges occur in all oceans and have a wide distribution from tropical to temperate to arctic regions. They frequently produce large quantities of secondary metabolites to deter potential predators and to inhibit the growth of fouling organisms, and thus become one of important sources of bioactive marine natural products.In the process of searching for bioactive compounds, we have successively investigated three species of marine sponges collected off the Lingshui Bay, Hainan Province, China. By repeatedly chromatography on gel Sephadex LH-20 and silica gel columns, as well as purification by RP-HPLC, 51 compounds were obtained from the acetone extracts of the three species, including 24 sesquiterpens, 22 sesterterpenes, 1 triterpene, 3 indole compounds and 1 sterol. The structures of the compounds were elucidated on the basis of extensive spectroscopic analysis and comparison with reported data, one of which was secured by X-ray diffraction analysis experiment. Ten of the metabolites were identified as new compounds, and three were isolated from the natural source for the first time. The interesting fact is that the new spiro-sesquiterpene could convert to its dimer in dauterated chloroform solution under room temperature, which was further confirmed by X-ray diffraction analysis.All the compounds were subjected to a series of bio-screening experiments. Heteronemin was found to be cytotoxic against A-549, HL-60, HELA and BEL-7402 with IC_(50) of 2.31×10~(-10)M, 1.92×10~(-7)M, 2.42×10~(-6)M and 1.72×10~(-8)M, respectively. Hyrtiosal, 12, 18-diepiscalaradial, and scalarafuran were found to show inhibitory activity against PTP1B with IC_(50) of 6.04×10~(-5)M, 3.16×10~(-5)M, and 5.42×10~(-5)M, respectively.
引文
[1] Burkhard Haefner Drugs from the deep, marine natural products as drug candidates DDT 2003, 8, (12), 536-544
[2] D. John Faulkner Highlights of marine natural products chemistry (1972-1999) Nat. Prod. Rep. 2000, 17, 1-6
[3] John W. Blunt, Brent R. Copp, Murray H. G. Munro, Peter T. Northcote and Michele R. Prinsep Marine natural products Nat. Prod. Rep. 2005, 22, 15-61
[4] Hallock Y, Cardellina J H, Boyd M R. (-)-Frondosins A and D, HIV-innibitory sesquiterpene hydroquinone derivatives from Euryspongia sp. Nat. Prod. Lett., 1998, 11, 153-157
[5] Guzman de F S, Copp B R, Mayne C L, et al. Bolinaquinone, A novol cytotoxic sesquiterpene hydroquinone from a Philipine Dysidea sponge J. Org. Chem., 1998, 63, 8042-8044
[6] Goclik E, Konig G M, Wright A D, et al. Pelorol from the tropical marine sponge Dactylospongia elegans J. Nat. Prod, 2000, 63, 1150-1152
[7] Kwak J H, Schmitz F J, Kelly M. Sesquiterpene quinols/quinines from the Micronesian sponge Petrosaspongia metachromia J. Nat. Prod., 2000, 63, 1153-1156
[8] Salmoun M, Devijver C, Daloze D, et al. New sesquiterpene quinones from two sponges of the genus Hyrtios J. Nat. Prod, 2000, 63, 452-453
[9] R. Kazlauskas, P. T. Murphy and R. J. Wells Two Sesquiterpene Furans with new carbocyclic ring systems and related thiol acetates from a speciese of the sponge genus Dysidea Tetrahedron Lett. 1978, 4951-4954
[10] Clark J R, Garson M J, Brereton M I, et al. Vinylfurans revisited, a new sesquiterpene from Euryspongia delicilata J. Nat. Prod, 1999, 62, 915-917
[11] Flowers A E, Garson M J, Byriel K A, et al. Two new isonakafurans from the Great Barrier Reef sponge Dysidea sp. Nov Aust. J. Chem., 1998, 51,195-203
[12] Li C J, Schmitz F J, Kelly M. New nitrogenous bisabolene-type sesquiterpenes from a Micronesian marine sponge, Axinyssa species J. Nat. Prod., 1999, 62, 1330-1331+
[13] Mary J. Garson and Jamie S. Simpson Marine isocyanides and related natural products-structure, biosynthesis and ecology Nat. Prod. Rep. 2004, 21, 164-179
[14] Li C J, Schmitz F J, Kelly-Borges M. New diterpene lactones from the sponge Spongia matamata J. Nat. Prod, 1998, 61,546-547
[15] Li C J, Schmitz F J, Kelly-Borges M. Six new diterpenes from the sponge spongia matarnata J. Nat. Prod., 1999, 62, 287-290
[16] Mitchell S S, Harper M K, Faulkner D J. Spongiabutenolides A-D, minor γ-hydroxybutenolide diterpenoids from a Phillippines Spongia sp. Tetrahedron Lett., 1999, 33, 10887-10891
[17] Hyosu M, Kimura J. Two new spongian diterpenes from Coscinoderma mathewsi J. Nat. Prod., 2000, 63, 422-423
[18] Oliveros M B, Edrada R A, Proksch P, et al. A new meroditerpenoid dimmer from an undescribed Philippine marine sponge of the genus Strongylophora. J. Nat. Prod., 1998, 61, 948-952
[19] Wolf D, Schmitz F J. New diterpene isomitriles from the sponge Phakellia pulcherrima, J. Nat. Prod., 1998, 61, 1524-1527
[20] Miyaoka H, Shimomura M, Kimura H, et al. Antimalarial activity of kalihinol A and new relative diterpenoids from the Okinawan sponge, Acanthella sp.. Tetrahedron, 1998, 54, 13467-13474
[21] Ciavatta M L, Fontana A, Puliti R, et al. Structures and absolute stereochemistry of isocyanide and isothiocyanate amphilectenes from the Caribbean sponge Cribochalina sp. Tetrahedron, 1999, 55, 12629-12636
[22] Clark R J, Stepleton B L, Garson M J. New isocyano and isothicyanato terpene metabolites from the tropical marine sponge Acanthella cavernosa. Tetrahedron, 2000, 56, 3071-3076
[23] Umeyama A, Nozaki M, Arihara S. Polasols A-C, three new diterpenes from the marine sponge Epipolasis sp.. J. Nat. Prod, 1998, 61,945-947
[24] Umeyama A, Machida M, Nozaki M, et al. Peroxypolasol and mugipolasol, two novel diterpenes from the marine sponge Epipolasis sp. J. Nat. Prod., 1998, 61, 1435-1436
[25] Fontana A, Ciavatta M L, Amodeo P, et al. Single solutione phase conformation of new antiproliferative cembranes Tetrahedron, 1999, 55, 1143-1152
[26] Fu X, Schmitz F J, Tanner R S, et al. Agelasines H and I, 9-methyladenine-containing diterpenoids from an Agelas sponge, J. Nat. Prod., 1998, 61, 548-550
[27] West L M, Northcote P T, Battershill C N. Two new clerodane diterpenes from the New Zealand marine sponge Raspailia sp. Aust. J. Chem., 1998, 51, 1097-1103
[28] Tasdemir D, ConcepciOn G P, Mangalindan G C, et al. New terpenoids from a Cacospongia sp. from the Philippines. Tetrahedron, 2000, 56, 9025-9030
[29] Tanaka J, Marriott G, Higa T, et al. Cacofurans A and B, new furanoditerpenes from a marine sponge, J. Nat. Prod, 2001, 64, 1468-1470
[30] Mcnally M, Capon R J. Phorbasin B and C, novel diterpenes from a southern Australian marine sponge, Phorbas species, J. Nat. Prod., 2001, 64, 645-647
[31] Vuong D, Capon R J. Phorbasin A, A novel diterpene from a southem Australian marine sponge, Phorbas speciles J. Nat. Prod., 2000, 63, 1684-1685
[32] Wellington K D, Cambie R C, Rutleddge P S, et al. Chemistry of sponges 19. novel bioactive metabolites from Hamigera tarangaensis J. Nat. Prod., 2000, 63, 79-85
[33] 曾陇梅，符雄．具有生物活性的二倍半萜的国外研究进展 中国海洋药物，1991，3，28-34
[34] Liu Y H, Bae B H, Alam N, et al. New cytotoxic sesterterpenes from the sponge Sarcotragus species J. Nat. Prod., 2001, 64, 1301-1302
[35] Kitsch G, Kong G M, Wright A D, et al. A new bioactive sesterterpene and antiplasmodial alkaloids from the marine sponge Hyrtios cf. erecta J. Nat. Prod., 2000, 63, 825-829
[36] Rosa S D, Crispino A, Giulio A D, et al. A new cacospongionolide inhibitor of human secretory phospholipase A_2 from the Tyrrhenian sponge Fasciospongia cavernosa and absolute configuration of cacospongionolides. J. Nat. Prod., 1998, 61, 931-935
[37] Rosa S D, Crispino A, Giulio A D, et al. A new cacospongionolide derivative from the sponge Fasciospongia cavernosa J. Nat. Prod., 1999, 62, 1316-1318
[38] Rosa S D, Crispino A, Giulio A D, et al. A novel C_(21) terpene lactone from the sponge Fasciospongia cavemosa. Tetrahedron, 1999, 55, 13805-13808
[39] Fu X, Ferreira M L G, Schmitz F J, et al. Halisulfate 7, a new sesterterpene sulfate from a sponge, Coscinoderma sp. J. Nat. Prod., 1999, 62, 1190-1191
[40] Musman M, Ohtani I I, Nagaoka D, et al. Hipposulfates A and B, new sesterterpene sulfates from an Okinawa sponge, Hippospongia cf. metachromia J. Nat. Prod., 2001, 64, 350-351
[41] Charan R D, Mckee T C, Boyd M R. Thoractandrols C, D and E, new sesterterpenes from the marine sponge thorectandra sp. J. Nat. Prod., 2002, 65,492-494
[42] Randazzo A, Debitus C, Minale L, et al. Petrosaspongiolides M-R, new potent and selective phospholipase A_2 inhibitors from the New Caledonian marine sponge Petrosaspongia nigra. J. Nat. Prod., 1998, 61, 571-575
[43] Kondracki M L B, Longeon A, Debitus C, et al. New cytotoxic isomalabaricane-type sesterterpenes from the New Caledonian marine sponge Rhabdastrella globostellata. Tetrahedron Lett., 2000, 41, 3087-3091.
[44] Buchanan M S, Edser A, King G, et al. Cheilanthane sestderterpenes, protein kinase inhibitors, from a marine sponge of the genus Ircinia J. Nat. Prod., 2001, 64, 300-304
[45] Hanson J R. The sestertepenoids. Nat. Prod. Rep., 1996, 2, 529-547
[46] Tsuchiya N, Sato A, Hata T, et al. Cytotoxic scalarane sesterterpenes from a sponge, Hyrtios erecta J. Nat. prod., 1998, 61,468-473
[47] Miyaoka H, Nishijima S, Mitome H, et al. Three new scalarane sesterterpenes from the Okinawa sponge Hyrios erectus J. Nat. Prod., 2000, 63, 1684-1685
[48] Cambie R C, Rutledge P S, Yang X S, et al. Chemistry of sponges . 18. 12-desacetylfuroscalar-16-one, a new sesterterpene from a Cacospongia sp. J. Nat. Prod., 1998, 61, 1416-1417
[49] Rosa S D, Crispino A, Guilio A D, et al. A new dimethylscalaraen derivative from the sponge Cacospongia scalaris Tetrahedron, 1998, 54, 6185-6190
[50] Jahn T, KOnig G M, Wright A D. Three new scalarane-based sesterterpenes from the tropical marine sponge Strepsichordaia lendenfeldi. J. Nat. Prod., 1999,62, 375-377
[51] Simpson J C, Daloze D, Kaisin M, et al. Ichthyotoxic sesterterpenoids from the Neo Guinean sponge Carteriospongia follascens Tetrahedron, 1985,41,4603-4614
[52] Fu X, Zeng L M, Su J Y, et al. Phyllofolactones C and D, two new minor homoscalarane sesterterpenes from the Chinese sponge Phyllospongia foliascens J. Nat. Prod., 1999, 62, 644-646
[53] Jimenez J I, Yoshida W Y, Scheuer P J, et al, Honulactones, new bishomoscalarane sesterterpenes from the Indoesian sponge Strepsichordaia aliena. J. Org. Chem., 2000, 65, 6837-6840
[54] Jimenez J I, Yoshida W Y, Scheuer P J, et al. Scalarane-based sesterterpenes from an Indonesian sponge Strepsichordaia aliena J. Nat. Prod., 2000, 63,1388.
[55] Youssef D T A, Yamaki R K, Kelly M, et al. salmahyrtisol A, a novel cytotoxic sesterterpene from the Red Sea sponge Hyrtois erecta. J. Nat. Prod., 2002, 65,2.
[56] Rohan Davis and Robet J. Capon Two new scalarane sesterterpenes: isoscalarafuran-A and -B,epimeric alcohols from a southern Australian Marine Sponge, Spongia hispida Aust. J. Chem. 1993, 46, 1295-1299
[57] Pettit G R, Cichacz Z A, Tan R, et al. Antineoplastic agents. 386. isolation of sesterstatins 1-3 from the marine sponge Hyrtios erecta J. Nat. Prod., 1998, 61,13-16
[58] Yan Qiu, Zhiwei Deng, Yuehu Pei, Hongzheng Fu, Jun Li, Peter Proksch, and Wenhan Lin Sesterpenoids from the Marine Sponge Hyrtios erectus J. Nat. Prod., 2004, 67, 921-924
[59] Oku N, Matusunaga S, Wada S, et al. New isomalabaricane triterpenes from the marine sponge Stellatta globostelltta that induce morphological changes in rat fibroblasters J. Nat. Prod., 2000,63, 205-209
[60] Zampella A, D'Auria M V, Debitus C, et al. New isomalabaricane derivatives from a new species of Jaspis sponge collected at the Vanuatu Islands J. Nat. Prod., 2000, 63, 943-946
[61] Meragelman K M, Mckee T C, Boyd M R. New cytotoxic isomalabaricane triterpenes from the sponge Jaspis species J. Nat. Prod., 2001, 64, 389-392
[62] Zhang W H, Che C T. Isomalabaricane-type nortriterpenoids and other constituents of the marine sponge Geodiajaponica J. Nat. Prod, 2001, 64, 1489-1492
[63] Blackburn C L, Hopmann C, Sakowicz R, et al. Adociasulfates 1-6, inhibitors of kinesin motor proteins from the sponge Haliclona sp. J. Org. Chem., 1999, 64, 5565-5570
[64] Kalaitzis J A, Leone P de A, Harris L, et al. Adociasulfates 1, 7, and 8, new bioactive hexaprenoid hydroquinone from the marine sponge Adocia sp. J. Org. Chem., 1999, 64, 5571-5574
[65] Kalaitzis J A, Quinn R J. Adociasulfate-9, a new hexaprenoid hydroquinone from the Great Barrier Reef sponge Adocia aculeate J. Nat. Prod, 1999, 62, 1682-1684
[66] Blackburn C L, Faulkner D J. Adociasulfate 10, a new merohexaprenoid sulfate from the sponge Haliclona sp.. Tetrahedron, 2000, 56, 8429-8432
[67] Crews P, Harrison B. New triterpene-ketides (merotriterpenes), haliclotriol A and B, from an Indo-Pacific Haliclona sponge. Tetrahedron, 2000, 56, 9039-9046
[68] Bokesch H R, Stull A C, Pannell L K, et al. A new pentacyclic sulfated hydroquinone from the marine sponge Haliclona sp. Tetrahedron Lett., 2002, 43, 3079-3082
[69] Costantino V, Fattorusso E, Imperatore C, et al. The first 12-methyihopanoid, 12-methylbacteriohopanetetrol from the marine sponge Plakortis simplex. Tetrahedron 2000, 56, 3781-3784
[70] Shatz M, Yoseif T, Kashman Y. Bacteriohopanehexol, a new triterpene from the marine sponge Petrosia species J. Nat. Prod, 2000, 63, 1554-1556
[71] Williams D E, Tahir A, Anderson R J. A new acyclic diketotriterpenoid isolated from the Indonesian marine sponge Hyrtios erectus. J. Nat. Prod, 1999, 62, 653-654.
[72] Wei Zhang, Song Xue, Quanyu Zhao, Xiaoying Zhang, Jinhe Li, Meifang Jin, Xinju Yu, Quan Yuan Biopotentials of marine sponges from China oceans: past and future Biomolecular Engineering 2003, 20, 413-419
[73] 黄孝春，郭跃伟 海绵药物的研究进展：化学和生物活性 中国天然药物 2005，3，(1)，1-9
[76] Dieter Enders, Thomas SchUBeler First Highly Efficent Asymmetric Synthesis of the Hyrtios Erectus Diketotriterpenoid Synthesis 2002, 15, 2280-2288
[77] Kazuo Iguchi, Yoshie Shimada, and Yasuji Yamada Hyrtiosal, a New Sesterterpenoid with a Novel Carbon Skeleton from the Okinawan Marine Sponge Hyrtios erectus J. Org. Chem. 1992, 57, 522-524
[78] Phillip Crews and Pedro Bescansa Sesterterpens from a Common Marine Sponge Hyrtios erecta J. Nat. Prod. 1986, 49, 1041-1052
[79] G. Cimino, S. De Stefano and A. Di. Luccia Further Sesterteroenes from the Sponge Spongia nitens, 12-epi-scalaradial and 12, 18-diepi-scalaradial Experientia 1979, 35, 1277-1278
[80] M. L. Bourguet-Kondracki, M. T. Martin, C. Debitus and M. Guyot 12-epi-Heteronemin : New Sesterterpene From The Marine Sponge Hyrtios erecta Tetrahedron Lett. 1994, 35, 109-110
[81] Roger P. Walker, Janice E. Thompson, and D. John Faulkner Sesterterpenes from Spongia idia J. Org. Chem. 1980, 45, 4976-4979
[82] R. Kazlauskas, P. T. Murphy, R. J. Quinn and R. J. Wells Heterronemin, a New Scalarin Type Sesterterpene from the Sponge Heterronema erecta Tetrahedron Lett. 1976, 30, 2631-2634
[83] Guido Cimino, Salvatore De Stefano, Luigi Minale, and Enrico Trivellone 12-epi-Scalarin and 12-epi-Deoxoscalarin, Sesterpenes from the Sponge Spongia Nitens J. C S. Perkin I 1977, 1587-1593
[84] Junichi Kobayashi, Tetsuya Murayama, Masami Ishibashi et al Hyrtiosins A and B, New Indole Alkaloids from the Okinawan Marine Sponge Hyrtios erectus Tetrahedron 1990, 46, 7699-7702
[85] 李莉娅，邓志威，李军，付宏征，林文翰 中国南海海绵Cinachyrella australiensis化学成分研究 北京大学学报(医学版)2004，36，(2)12-17
[86] Qing Lu and D. John Faulkner Two New Sesterterpenoids and a New 9, 11-Secosterol from Spongia matamata J. Nat. Prod. 1997, 60, 195-198
[87] Geonseek Ryu, Shigeki Matsunaga, and Nobuhiro Fusetani Three New Cytotoxic Sesterterpenes from the Marine Sponge Hyrtios cf. erectus J. Nat. Prod. 1996, 59, 515-517
[88] George M. Cameron, Bronwin L. Stapleton Shane M. Simonsen, Douglas J. Brecknell and Mary J. Garson New Sesquiterpene and Brominated Metabolites from the Tropical Marine Sponge Dysidea SP. Tetrahedron 2000, 56, 5347-5252
[89] Reddy, N. S. and Venkateswarlu, Y. Two New Sesquiterpenoids from the Marine Sponge Dysidea Fragilis, Indian J. Chem. Sect. B 1999, 38, 1002-1004.
[90] C. Charles, J. C. Braekman, D. Daldae, B. Tursch Chemical Studies of Marine Invertebrates, Herbadysidolide and Herbasolide, Two Unusual Sesquiterpenoids from the Sponge Dysidea herbacea Bull. Soc. Chim. Bilg. 1978, 87, 481-486
[91] Kazlauskas. R., Murphy, P. T. and Wells, R. J. A New Sesquiterpene from the Sponge Dysidea herbacea Tetrahedron Lett. 1978, 19, 4949-4950
[92] R. Kazlauskas, P. T. Murphy and R. J. Wells Two Sesquiterpene Furans with New Carbocyclic Ring Systems and Related Thiol Acetates from a Speciese of the Sponge Genus Dysidea Tetrahedron Lett. 1978, 4951-4954
[93] Stephen H. Grode and John H. Cardellina Ⅱ Sesquiterpenes from the Sponge Dysidea etheria and the Nudibranch Hypselodoris zesra J. Nat. Prod. 1984, 47, (1), 76-83
[94] 肖定军，邓松之，曾陇海南海海绵Clathria fasciculate化学成分的研究(Ⅰ)中国海洋药物2002，21 (2), 1-4
[95] Janice E. Thompson, Roger P. Walker, Stepher J. Wratten, D. John Faulkener A Chemical Defense Mechanism For the Nudibranch Cadlida Luteomarginata Tetrahedron 1982, 38(13), 1865-1873
[96] George M. Cameron, Bronwin L. Stapleton Shane M. Simonsen, Douglas J. Brecknell and Mary J. Garson New Sesquiterpene and Brominated Metabolites from the Tropical Marine Sponge Dysidea SP. Tetrahedron 2000, 56, 5347-5252
[97] Timothy J. Schram and John H. Cardellina II An Unusual β, γ-Epoxy γ-Lactone from the Sponge Dysidea etheria J. Org. Chem. 1985, 50, 4155-4157
[98] Andreas Brust and Mary J. Garson Advanced Precursors in Marine Biosynthetic Study. Part 3, The Biosynthesis of dichloroimines in the Tropical Marine Sponge Stylotella aurantium Tetrahedron Lett. 2003, 44, 327-330
[99] Brian W. Sullivan and D. John Faulkner (6R, 7S)-7-Amino-7,8-dihydro-α-bisabolene, an Antimicrobial Metabolite from the Marine Sponge Halichondria sp. J. Org. Chem. 1986, 51, 5134-5136
[100] Nanda K. Gulavita, E. Dilip de Silva, Mark R. Haggadone, Peter Karuso, and Paul J. Scheuert Nitrogenous Bisabolene Sesquiterpenes from Marine Invertebrates J. Org. Chem. 1986, 51, 5136-5139
[101] Jamie S. Simpson, Andreas Brust and Mary J. Garson Biosynthetic Pathways to Dichloroimines; Precursor Incorporation Studies on Terpene Metabolites in the Tropical Marine Sponge Stylotella aurantium Org. Biomol.Chem. 2004, 2, 949-956
[102] E. Fattorusso, S. Magno, L. Mayol, C. Santacroce and D. Sica New Sesquiterpenoids from the Sponge Axinella Cannabina Tetrahedron 1975, 269-270
[103] B. J. Burreson, C. Christophersen and P. J. Scheuer Co-occurrence of Two Terpenoid Isocyanide-Formamide Pairs in a Marine Sponge (Halichondria sp.) Tetrahedron 1975, 2015-2018
[104] Hiroshi Hirota, Yasuhiko Tomono, and Nobuhiro Fusetani Terpenoids with Antifouling Activity Against Barnacle Larvae from the Marine Sponge Acanthella cavernosa Tetrahedron 1996, 52,2359-2368
[105] B. Di Blasio, E. Fattorusso, S. Magno, L. Mayol, C. Pedone, C. Santacroce and D. Sica Axisonitrile-3, Axisothiocyanate-3 and Aximide-3. Sesquiterpenes with a Novel Spiro[4,5]Decane Skeletonfrom the Sponge Axinella cannabina Tetrahedron 1976, 32, 473-478
[106] Hidemichi Mitome, Nao Shirato, Hiroaki Miyaoka, Yasuji Yamada and Rob W. M. van Soest Terpene Isocyanides, Isocyanates, and Isothiocyanates from the Okinawan Marine Sponge Stylissa sp. J. Nat. Prod. 2004, 67, 833-837
[107] Robert J. Capon and John K. Macleod New Isothiocyanate Sesquiterpenes from the Australian Marine Sponge Acanthella Pulcherrima Aust. J. Chem. 1988, 41, 979-983
[108] Patrizia Ciminiello, Ernesto Fattorusso, Silvana Magno, and Luciano Mayol New Nitrogenous Sesquiterpenes Based on Alloaromadendrane and Epi-eudesmane Skeletons from the Marine Sponge Axinella cannabina CAN. J. CHEM. 1987, 65, 518-522
[109] Hai-yin He, Javier Salva, Robert F. Catalos, and D. John Faulkner Sesquiterpene Thiocyanates and Isothiocyanates from Axinyssa aplysinoides J. Org. Chem. 1992, 57, 3191-3194
[110] Luciano Mayol, Vincenzo Piccialli and Donato Sica Nitrogenous Sesquiterpenes from the Marine Sponge Acanthella Acuta, Three New Isocyanide-Isothiocyanate Pairs Tetrahedron 1987, 43,(22), 5381-5388
[111] 邱彦，邓志威，裴月湖，付宏征，林文翰 中国南海海绵Hytios erectus中二倍半萜类化学成分 中国天然药物2003，1，(3)，137-141
[112] 严小红，郭跃伟中国南海海绵Acanthella sp．化学成分的研究 天然产物研究与开发2003，15，(3)，199-202