摘要
由于陆生环境日益恶化，陆生资源日益匮乏，严重威胁人类生命健康的疑难病症频频发生，对新药的需求与日俱增。因此，人们把寻求新药的希望寄托在海洋这个特殊的生态系统。高压、高盐、低温、缺氧等特殊的海洋生态环境造就了海洋生物的特殊性和多样性，赋予了海洋天然产物结构的多样性和新颖性。结构多样的海洋天然产物也具有独特、显著的生物活性。其中，相当一部分海洋天然产物具有抗菌活性。研究表明海洋无脊椎动物及其共附生微生物是丰富的抗菌资源。本研究以三株海洋来源真菌及四种短指软珊瑚为研究对象，以抗菌活性筛选为指导，进行次级代谢产物研究，以期获得具有抗菌活性的化合物，从而为海洋活性天然产物以及海洋药物先导化合物的筛选和发现提供基础资料。
本研究对3株海洋来源的真菌，青霉属真菌(Penicillium sp.)，茎点属真菌(Phoma sp.)，黄蓝状菌(Talaromyces sp.)和4种同时、同地采集的短指软珊瑚(Sinularia sp.)为研究对象，综合运用正、反相硅胶柱层析，SephadexLH-20凝胶柱层析及半制备HPLC等分离手段，NMR、MS、IR、UV、CD等波谱学技术，并结合化学方法，分离并鉴定了110个化合物，其中新化合物21个(1–3,6–8,11–14,36–38,40,50,66,80,81和91)。涉及9种结构类型，包括：异香豆素及苯并呋喃类化合物21个，色原酮类化合物10个，联苯醚类化合物6个，甾体化合物40个，萜类化合物11个，芳香族化合物7个，含氮化合物12个，醌类化合物2个以及内酯类化合物1个。从真菌Penicillium sp.中发现了仅在C-4位有取代基，而C-3位没有取代基的罕见的异香豆素类化合物(1,1A-1和1A-2)，运用Mosher法及CD量化计算的方法确定了化合物的绝对构型；从该菌中还发现含脂肪侧链的异香豆素类化合物(2–5)，通过与相似化合物比较CD谱图，结合Mosher法，确定了其绝对构型。从短指软珊瑚Sinularia sp.中首次分离获得了芳香化的amphilectane-type二萜化合物(80和81)。
对分离获得的部分化合物进行了抗菌活性评价，此外还通过细胞毒、抗藤壶幼虫附着、斑马鱼胚胎毒性和卤虫致死等生物活性模型，对分离获得的单体化合物进行了生物活性评价，发现具有抗菌、细胞毒活性的化合物25个；具有抗藤壶幼虫附着、卤虫致死以及斑马鱼胚胎毒活性的化合物24个。Amphilectane二萜类化合物对Escherichia coli， Staphylococcus albus以及Vibrio anguillarum的抑制活性与阳性药环丙沙星相当，其中化合物80对S. albus的MIC为0.156μM，强于阳性药(MIC0.312μM)的活性。甾体类化合物15，18，21和22对鳗弧菌(Vibrio anguillarum)显示了强的抗菌活性，其MIC分别为0.39,0.78,0.78和0.39μM。甾体四环系统中的酮羰基、环氧以及过氧环基团是甾体类化合物抗菌活性的有效官能团。联苯醚类化合物显示了较强的抗菌活性，其中化合物39的抗菌活性明显高于化合物36和38的活性，表明苯环上甲氧基取代和糖基化作用会导致抗菌活性的减弱。除此之外，异香豆素类化合物2，4，5和7对斑马鱼胚胎的24h卵凝结的EC50值分别为6.42，5.68，8.87和7.13μg/mL，对斑马鱼胚胎72h致死IC50值分别为4.07，3.95，6.48和4.15μg/mL。构效关系研究发现，异香豆素类化合物C-3位脂肪侧链的存在和C-4位羟甲基的乙酰化增强了化合物的斑马鱼胚胎毒活性，C-7位被羟基取代后活性明显降低。研究结果表明，异香豆素及苯并呋喃类化合物、9,11-开环甾体、发生电子迁移的甾体类化合物以及联苯醚类化合物显示了多种生物学活性。
对相同时间采自相同地域的四种短指软珊瑚Sinularia sp.1(GX-WZ-27-49)，Sinularia sp.2(GX-WZ-32-47)，Sinularia sp.3(GX-WZ-28-33)，Sinularia sp.4(GX-WZ-46)中的次级代谢产物进行了比较研究。结果表明，相同时间采自相同地域的同属不同种的短指软珊瑚的次级代谢产物结构类型存在差异，包括9,11-开环甾体、amphilectane二萜、孕甾、过氧化倍半萜等多种结构类型。本发现对该属短指软珊瑚的化学分类学研究具有一定的借鉴意义。
综上所述，本研究通过抗菌活性筛选和化学筛选，从三株海洋来源真菌和四种短指软珊瑚中分离获得了结构类型丰富多样的海洋天然产物，运用Mosher法及ECD法确定了化合物的绝对构型。抗菌活性构效关系初步表明共轭酮羰基、环氧及过氧环基团是甾体类化合物的有效官能团。Amphilectane二萜的芳香化可以增强其抗菌活性。生物活性筛选评价表明，分离获得的化合物具有综合的化学生态学效应。本研究发现了海洋来源真菌和短指软珊瑚中的次级代谢产物具有丰富多样的结构类型和显著的抗菌活性，为海洋抗菌药物先导化合物的开发应用研究提供了化合物基础。
Since terrestrial environment is deteriorating, terrestrial resources areincreasingly scarce, and the incurable diseases, a serious threat to human life andhealth, occur frequently. The demand for new drugs is increasing. Therefore, the hopeof seeking new drugs was put on the marine ecology environment. Marine ecologyenvironment which have a high pressure, high salt, hypothermia, hypoxia and otherspecial environmental characteristics may create abundant biodiversity which can beendowed with unique chemical diversity and distinct bioactivities. Among them, avariety of marine natural products exhibited antibacterial activities. Marineinvertebrates and microorganisms from coral reef ecosystem, rich in antibacterialsecondary metabolites, have become important bioresources for screening anddiscovery of lead compounds and marine drugs. In this study, the chemical diversityand antibacterial activity of secondary metabolites of three marine-derived fungi andfour soft corals Sinularia sp. have been investigated. These researches providedfoundations for the screening and discovery of bioactive marine natural products andlead compounds of marine drugs.
In this study, under the guidance of the chemical and bioactive screening, threemarine-derived fungi including Penicillium sp., Phoma sp., Talaromyces sp. and foursoft corals Sinularia sp. collected from the same area at the same time wereinvestigated for their bioactive secondary metabolites. The compounds were isolatedby column chromatography on silica gel, Sephadex LH-20and preparative reversedphase HPLC, and identified by spectroscopy of NMR, MS, IR, UV, CD as well aschemical methods. From these organisms,110compounds were obtained, including 21new compounds (1–3,6–8,11–14,36–38,40,50,66,80,81and91). More than9structural types were found, including21isocoumarins and benzofurans,10chromones,6diphenyl ethers,40steroids,11terpenoids,7aromatic compounds,12nitrogen compounds,2quinone derivatives and1lactone. Compounds1,1A-1and1A-2were isolated from the sponge-derived fungus, Penicillium sp., which representa rare naturally occurring isocoumarin derivative with4-substitution, but nosubstituent at the3-position. The relative and absolute configurations of1weredetermined by quantum chemical calculation of its ECD spectrum combined with themodified Mosher’s method. The isocoumarins (2–5) with side chain at C-3, were alsoobtained from the Penicillium sp. fungus. The absolute configurations of compounds2–5were assigned by the modified Mosher’s method together with comparison of CDspectra. The new aromatic amphilectane-type diterpenes (80and81) were isolatedfrom Sinularia sp. for the first time.
The isolated compounds were evaluated their antibacterial activity and otheractivities by various of screening modles including antifouling, ichthyotoxic, lethalityand so on. A variety of bioactive compounds had been found, including25antibacterial and cytotoxic activity compounds and24antifouling, lethality activity,and ichthyotoxic activity compounds. Amphilectane-type diterpenes showed stronginhibitory activity against Escherichia coli, Staphylococcus albus and Vibrioanguillarum. Compound80displayed strong inhibitory activity against S. albus withan MIC value of0.156μM, which was stronger than that of the positive controlciprofloxacin (MIC0.312μM). Steroids15,18,21and22exhibited inhibitory activityagainst Vibrio anguillarum with MIC values of0.39,0.78,0.78and0.39μM,respectively, which were stronger than or equivalent to that of the positive controlciprofloxacin. The results of antibacterial activity suggested that the ketone carbonylgroups, epoxy rings and peroxy groups in steroids played apparent role on theantibacterial activity. The diphenyl ethers exhibited antibacterial activity. Compound39displayed better potent antibacterial activity than compounds36and38, with thesubstituted methoxy and hexose residue. These results indicated that the antibacterialactivity might be weakened due to the substituent of methoxy and hexose residue. And the isocoumarins2,4,5and7displayed24h coagulated eggs of zebrafish at theconcentrate of6.42,5.68,8.87and7.13μg/mL,72h death of zebrafish at theconcentrate of4.07,3.95,6.48and4.15μg/mL, respectively. The study ofstructure-activity relationships about isocoumarins showed that the presence of3-substituted side chain and the acetylation of hydroxymethyl at C-4increased thezebrafish toxicity. The substituted hydroxyl at C-7probably weakened thezebrafish toxicity. The bioactive results indicated that isocoumarins, benzofurans,9,11-secosterols,13(14→8)abeo-8-ergostane and diphenyl ethers exhibited a varietyof biological activities.
The secondary metabolites of four soft corals Sinularia sp.1(GX-WZ-27-49),Sinularia sp.2(GX-WZ-32-47), Sinularia sp.3(GX-WZ-28-33), Sinularia sp.4(GX-WZ-46) collected from the same area at the same time were compared andanalyzed. It indicated that the different species in Sinularia genus collected from thesame area at the same time shared similarities and differences. The secondarymetabolites included many structural types, such as9,11-secosterols,amphilectane-type diterpenes, pregnane, cyclic sesquiterpene peroxides, and so on. Itsupplied foundation for further investigation for the chemotaxonomic significance ofthe Sinularia genus.
In conclusion, in present study under the guidance of the chemical and bioactivescreening, bioassay-guided fractionation of three marine-derived fungi and four softcorals Sinularia sp. led to the isolation of a variety of bioactive natural products. Theabsolute configurations of isocoumarins were assigned by the modified Mosher’smethod and TDDFT ECD calculation together with comparison of CD spectra. Theresults of antibacterial activity suggested that the ketone carbonyl groups, epoxy ringsand peroxy groups in steroids played apparent role on the antibacterial activity. Thearomatization of amphilectane-type diterpenes increased the antibacterial activity. Theresults of bioactive evaluation indicated that the isolated compounds exhibited avariety of biological activities, and some compounds have been found to possessecological activity and pharmacological activities at the same time. The studyindicated that the secondary metabolites of marine-derived fungi and soft corals display chemical diversity and pronounced antibacterial activity. It providedfoundations for the discovery and exploration of antibacterial marine natural products.
引文
[1] Blunt J W, Copp B R, Keyzers R A, et al. Marine natural products. Nat. Prod. Rep.,2012,29:144~222, and previous reviews in the series.
[2] Pettit R, Woyke T, Pon S, et al. In vitro and in vivo antifungal activities of the marine spongeconstituent spongistatin. Med. Mycol.,2005,43(5):453~463.
[3] Bewley C A, Debitus C, Faulkner D J. Microsclerodermins A and B. Antifungal cyclic peptidesfrom the lithistid sponge Microscleroderma sp. J. Am. Chem. Soc.,1994,116(17):7631~7636.
[4] Kernan M R, Faulkner D J. Halichondramide, an antifungal macrolide from the spongeHalichondria sp. Tetrahedron Lett.,1987,28(25):2809~2812.
[5] Wang C Y, Geng M Y, Guan H S. Current and future trends in the investigation of marinedrugs. Chin. J. New. Drugs,2005,14(3):278~282.
[6] Bugni T S, Ireland C M. Marine-derived fungi: a chemically and biologically diverse group ofmicroorganisms. Nat. Prod. Rep.,2004,21:143~163.
[7]韩磊，四种南海珊瑚与两种内生真菌中次级代谢产物及其化学生态学作用：[博士学位论文].青岛:中国海洋大学医药学院,2011.
[8] Scudiero D A, Shoemaker R H, Paull K D, et al. Evaluation of a soluble tetrazolium/formazanassay for cell growth and drug sensitivity in culture using human and other tumor cell lines.Cancer Res.1988,48:4827~4833.
[9] Appendio G, Gibbons S, Giana A, et al. Antibacterial cannabinoids from Cannabis sativa: Astructure-activity study. J. Nat. Prod.2008,71:1427~1430.
[1] Kito K, Ookura R, Yoshida S, et al. New cytotoxic14-membered macrolides frommarine-derived fungus Aspergillus ostianus. Org. Lett.,2008,10(2):225~228.
[2] Shao C L, Wang C Y, Zheng C J, et al. A new anthraquinone derivative from the marineendophytic fungus Fusarium sp.(NO. b77). Nat. Prod. Res.2010,24(1):81~85.
[3] Takamatsu S, Hiraoka H, Kim Y P, et al. Macrosphelides C and D, novel inhibitor of celladhesion. J. Antibiot.,1997,50(10):878~880.
[1] Tsuda M, Kasai Y, Komatsu K, et al. Citrinadin A, a novel pentacyclic alkaloid frommarine-derived fungus Penicillium citrinum. Org. Lett.,2004,6(18):3087~3089.
[2] Chen L, Fang Y C, Zhu T J, et al. Gentisyl alcohol derivatives from the marine-derived fungusPenicillium terrestre. J. Nat. Prod.,2008,71(1):66~70.
[3] Tsuda M, Sasaki M, Mugishima T, et al. Scalusamides A-C, new pyrrolidine alkaloids fromthe marine-derived fungus Penicillium citrinum. J. Nat. Prod.,2005,68(2):273~276.
[4] Bringmann G, Lang G, Gulder T A M, et al. The first sorbicillinoid alkaloids, the antileukemicsorbicillactones A and B, from a sponge-derived Penicillium chrysogenum strain Tetrahedron,2005,61:7252~7265.
[5] Xin Z H, Tian L, Zhu T J, et al. Isocoumarin derivatives from the sea squirt-derived fungusPenicillium stoloniferum QY2-10and the halotolerant fungus Penicillium notatum B-52. Arch.Pharm. Res.,2007,30(7):816~819.
[6] Larsen T O and Breinholt J. Dichlorodiaportin, Diaportinol, and Diaportinic Acid: Three novelisocoumarins from Penicillium nalgiovense. J. Nat. Prod.,1999,62(8):1182~1184.
[7] Bode H B, Bethe B, Zeeck A, et al. Big effects from small changes: Possible ways to explorenature′s chemical diversity. Chem. Bio. Chem.,2002,3(7):619~627.
[8] Spartan04; Wavefunction Inc.: Irvine, CA.
[9] Gaussian09, Revision A.1, M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A.Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, H. Nakatsuji,M. Caricato, X. Li, H. P. Hratchian, A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M.Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O.Kitao, H. Nakai, T. Vreven, J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro, M. Bearpark, J. J.Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Kobayashi, J. Normand, K.Raghavachari, A. Rendell, J. C. Burant, S. S. Iyengar, J. Tomasi, M. Cossi, N. Rega, J. M.Millam, M. Klene, J. E. Knox, J. B. Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin, K.Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg, S. Dapprich, A. D.Daniels, O. Farkas, J. B. Foresman, J. V. Ortiz, J. Cioslowski, and D. J. Fox, Gaussian, Inc.,Wallingford CT,2009.
[10] Stephens P J, Harada N. ECD Cotton effect approximated by the Gaussian curve and othermethods. Chirality,2010,22,229~233.
[11] Kusumi T, Fujita Y, Ohtani I, et al. Anomaly in the modified Mosher’s method: absoluteconfigurations of some marine cembranolides. Tetrahedron Lett.1991,32(25):2923~2926.
[12] Li S D, Wei M Y, Chen G Y, et al. Two new dihydroisocoumarins from the endophyticfungus Aspergillus sp. collected from the South China Sea. Chem. Nat. Comp.,2012,48:371~373.
[13] Choukchou-Braham N, Asakawa Y, Lepoittevin J P. Isolation, structure determination andsynthesis of new dihydroisocoumarins from Ginkgo bilobu L. Tetrahedron Lett.1994,35(23):3949~3952.
[14] Chinworrungsee M, Kittakoop P, Isaka M, et al. Halorosellins A and B, unique isocoumaringlucosides from the marine fungus Halorosellinia oceanica. J. Chem. Soc., Perkin Trans.1.2002,2473~2476.
[15] Schlegel B, Hartl A, Gollmick F A, et al.7-methoxy-2,3-dimethylbenzofuran-5-ol, a newantioxidant from Malbranchea cinnamomea HKI0286. J. Antibiot.2003,56(9):792~794.
[16] Barrero A F, Cabrera E, Rodriguez I, et al. Alkylresorcinols and isocoumarins from ononispubescens. Phytochemistry,1994,35(2):493~498.
[17] Findlay J A, Li G, Miller J D, et al. Insect toxins from spruce endophytes. Can. J. Chem.2003,81:284~292.
[18] Amagata T, Tanaka M, Yamada T, et al. Variation in cytostatic constituents of asponge-derived Gymnascella dankaliensis by manipulating the carbon source. J. Nat. Prod.,2007,70:1731~1740.
[19] Wang F Z, Fang Y C, Zhang M,et al. Six new ergosterols from the marine-derived fungusRhizopus sp. steroids,2008,73,19~26.
[20] Nishitoba T, Sato H, Oda K, et al. Novel triterpenoids and a steroid from the fungusGanoderma lucidum, Agric. Biol. Chem.,1988,52(1):211~216.
[21] Della Greca M, Monaco P, Previtera L. Stigmasterols from typha latzfolza, J. Nat. Prod.,1990,53(6):1430~1435.
[22] Kwon H C, Zee S D, Cho S Y, et al. Cytotoxic ergosterols from Paecilomyces sp. J300, Arch.Pharm. Res.,2002,25(6):851~855.
[23]张敏，唐旭利，李国强.滨海湿地耐盐植物二色补血草化学成分研究.中国海洋大学学报自然科学版,2010,40(5):89~92.
[24] Kawagishi H, Katsumi R, Sazawa T, et al. Cytotoxic steroids from the mushroom Agaricusblazei, Phytochemistry,1988,27(9):2777~2779.
[25] Shu R G, Wang F W, Yang Y M, et al. Antibacterial and xanthine oxidase inhibitorycerebrosides from Fusarium sp. IFB-121, an endophytic fungus in quercus variabilis. Lipids,2004,39(7):667~673.
[26]陈雪松，陈迪华，刘柯.脑甙类化合物的研究概况.天然产物研究与开发,2001,13(2):63~68.
[27]高锦明，沈杰，杨雪等.黄白红菇的化学成分.云南植物研究,2001,23(3):385~393.
[28] Jinichiro K, Toyozo Y, Masaru S, et al. Cerebrosides A and C, sphingolipid elicitors ofhypersensitive cell death and phytoalexin accumulation in rice plants. J. Bio. Chem.,1998,273(48):31985~31991.
[29]张鞍灵，刘国强，高锦明.脑苷脂B的结构鉴定.西北植物学报,2001,21(4):684~688.
[30]王文良，耐盐微生物的分离及两株耐盐真菌次级代谢产物的研究：[博士学位论文].青岛：中国海洋大学医药学院，2008.
[31] Sitrin R D, Chan G, Dingerdissen J, et al. Isolation and structure determination ofPachybasium cerebrosides which potentiate the antifungal activity of aculeacin. J. Antibiotic.,1988,41(4):469~480.
[32] Ballantine J A, Hassal C H, Jones B D. Some phenolic metabolites of mutant strains ofAspergillus rugulosus. Phytochemistry,1968,7:1529~1534.
[33] Itabashi T, Nozawa K, Nakajima S, et al. A new azaphilone, falconensin H, from Emericellafalconensis. Chem. Pharm. Bull.,1993,41(11):2040~2041.
[34]王涛，姜锡然，裴月湖等.云南土壤真菌07-11号菌株中的活性成分.中国药物化学杂志,2001,11(6):333~335.
[35] Srivastava R M, Brinn I M, Juan O, et al. Benzamidoximes: structural, conformational andspectroscopic studies. Journal of Molecular Structure,1997,406:159~167.
[36] Ui H, Shiomi K, Yamaguchi Y, et al. Nafuredin, a novel inhibitor of NADH-fumaratereductase, produced by Aspergillus niger FT-0554. J. Antibiot.,2001,54(3):234~238.
[37] Arunpanichlert J, Rukachaisirikul V, Sukpondma Y, et al. Azaphilone and isocoumarinderivatives from the endophytic fungus Penicillium sclerotiorum PSU-A13. Chem. Pharm.Bull.,2010,58(8):1033~1036.
[38] Zhang W, Krohn K, Draeger S, et al. Bioactive isocoumarins isolated from the endophyticfungus Microdochium bolleyi, J. Nat. Prod.,2008,71:1078~1081.
[39] Tsukada M, Fukai M, Miki K, et al. Chemical constituents of a marine fungus, Arthriniumsacchari. J. Nat. Prod.,2011,74:1645~1649.
[40] Fusetani N, Sugawara T, Mataunaga S. Cytotoxic metabolites of the marine sponge Mycaleadhaerens Lambel. J. Org. Chem.,1991,56(16):4971~4974.
[41] Nitta K, Yamamoto Y, Yamamoto I, et al. The metabolic products of Oospora (Oosporaastringenes). VI. Chemical structure of ospoglycol and its formation from oosponol byfungus. Agric. Biol. Chem.,1963,27(12):822~827.
[42](a) Nozawa K, Yamada M, Tsuda Y, et al. Antifungal activity of oospolactone, phyllodulcin,hydrangenol, and some other related compounds. Chem. Pharm. Bull.,1981,29(9):2689~2691.(b) Nitta K, Imai J, Yamamoto I, et al. The metabolic products of Oospora(Oospora astringenes). V. Determination of the chemical structure of oosponol by synthesis.Agric. Biol. Chem.,1963,27(12):817~821.(c) Nakajima S, Kawai K, Yamada S. Studies onfungal products. Part3. The identification of lenzitin as oosponol. Phytochemistry,1976,15(2):327.
[43] Aldrige D C, Grove J F, Turner W B.4-Acetyl-6,8-dihydroxy-5-methyl-2-benzopyran-1-one,a metabolite of Aspergillus viridinutans. J. Chem. Soc. C,1966,(2):126~129.
[44] Kimura Y, Nakadoi M, Shimada A, et al. Biosyntheses of sescandelin and sescandelin B: newisocoumarin compounds produced by the fungus, Sesquicillium candelabrum. Biosci.Biotechnol. Biochem.,1994,58(8):1525~1526.
[45] Lee J H, Park Y J, Kim H S, et al. Anti-angiogenic activities of novel isocoumarins, AGI-7and sescandelin. J. Antibiot.,2001,54(5):463~466.
[46] Cao Y J, Wei X Y, Xu H H, et al. Antifungal properties of methanol extract and its activecompounds from Brickellia rosmarinifolia Vent, Fitoterapia,2010,81:1176~1179.
[47] Rukachaisirikul V, Rodglin A, Sukpondma Y, et al. Phthalide and isocoumarin derivativesproduced by an Acremonium sp. isolated from a mangrove Rhizophora apiculata, J. Nat.Prod.,2012,75:853~858.
[48] Takenaka Y, Tanahashi T, Nagakura N, et al. Three isocoumarins and a benzofuran from thecultured lichen mycobionts of Pyrenula sp. Phytochemistry,2004,65:3119~3123.
[49] Krohn K, Florke U, Rao M S, et al. Metabolites from fungi15. New isocoumarins from anendophytic funfus isolated from the Canadian thistle Cirsium arvense. Nat. Prod. Lett.,2001,15(5):353~361.
[50](a) Canonica L, Danieli B, Lesma G, et al. Unusual photochemical behavior of the enonechromophore of the insect molting hormone20α-hydroxyecdysone. J. Chem. Soc.,Chem.Commun.1985,(19):1321~1322.(b) Canonica L, Danieli B, Lesma G, et al. Iron(II)-induced fragmentation reaction of γ-hydroperoxy-α,β-enones. Part1. Synthesis of13(14→8)-abeo steroids. Helv. Chim. Acta,1987,70(3):701~716.
[51] Amagata T, Doi M, Tohgo M, et al. Dankasterone, a new class of cytotoxic steroid producedby a Gymnascella species from a marine sponge, Chem. Commun,1999,1321~1322.
[52]申毅，邹建华，戴均贵.海洋红树林微生物土曲霉的代谢产物研究，2011,36(18):2515~2519.
[53] Barton D H R, Overton K H, Wylie A. Diterpenoid bitter principles. Part IV Investigations onthe constitution of palmarin. J. Chem. Soc.1962:4809~4815.
[54] Hori T, Kiang A K, Nakanishi K, et al. Structures of fibraurin and a minor product fromFibraurea chloroleuca. Tetrahedron,1967,23(6):2649~2656.
[55] Mohamed I E, Gross H, Pontius A, et al. Epoxyphomalin A and B, prenylated polyketideswith potent cytotoxicity from the marine-derived fungus Phoma sp. Org. Lett.,2009,11(21):5014~5017.
[56] Shim S H, Baltrusaitis J, Gloer J B, et al. Phomalevones A-C: dimeric and pseudodimericpolyketides from a fungicolous Hawaiian Isolate of Phoma sp.(Cucurbitariaceae). J. Nat.Prod.,2011,74:395~401.
[57] Zhang W, Krohn K, Egold H, et al. Diversity of antimicrobial pyrenophorol derivatives froman endophytic fungus, Phoma sp. Eur. J. Org. Chem.,2008,4320~4328.
[58] Sakurai M, Nishio M, Yamamoto K, et al. TMC-264, a novel antiallergic heptaketideproduced by the fungus Phoma sp. TC1674. Org. Lett.,2003,5(7):1083~1085.
[59] Zhang H, Yang F, Qi J, et al. Homoisoflavonoids from the Fibrous Roots of Polygonatumodoratum with Glucose Uptake-Stimulatory Activity in3T3-L1Adipocytes, J. Nat. Prod.2010,73:548~552.
[60] Kornsakulkarn J, Thongpanchang C, Lapanun S, et al. Isocoumarin glucosides from the scaleinsect fungus Torrubiella tenuis BCC12732, J. Nat. Prod.2009,72:1341~1343.
[61] Du L, Zhu T J, Liu H B, et al. Cytotoxic polyketides from a marine-derived fungusAspergillus glaucus, J. Nat. Prod.,2008,71:1837~1842.
[62] Yun B S, Cho Y, Lee I K, et al. Sterins A and B, New antioxidative compounds from Stereumhirsutum, J. Antibiot.,2002,55(2):208~210.
[63] Serianni A S, Barker R.[13C]-Enriched tetroses and tetrofuranosides: an evaluation of therelationship between NMR parameters and furanosyl ring conformation. J. Org. Chem.,1984,49(18):3292~3300.
[64]孙利，李冬利，陈玉婵等，南海海洋真菌帚状弯孢聚壳次级代谢产物及其抗肿瘤活性研究.中草药,2011,42(3):432~436.
[65] Weber H A, Gloer J B. Interference competition among natural fungal competitors: anantifungal metabolite from the coprophilous fungus Preussza flezschhakzz, J. Nat. Prod.,1988,51(5),879~883.
[66] Aly A H, Edrada-Ebel R A, Wray V, et al. Bioactive metabolites from the endophytic fungusAmpelomyces sp. isolated from the medicinal plant Urospermum picroides, Phytochemistry,2008,69:1716~1725.
[67] Lai S, Shizuri Y, Yamamura S, et al. Three new phenolic metabolites from penicilliumspecies. Heterocycles,1991,32(2):297~305.
[68] Yan H J, Gao S S, Li C S, et al. Chemical constituents of a marine-derived endophytic fungusPenicillium commune G2M, Molecules,2010,15:3270~3275.
[69]阙东枚，戴好富，曾艳波等，见血封喉内生真菌Acremonium sp. J1化学成分研究，中国药物化学杂志，2009,19(3):200~205.
[70] Notarov G, Piccialli V, Sica D. New steroidal hydroxyketones and closely related diols fromthe marine sponge clzona copzosa. J. Nat. Prod.,1992,55(11):1588~1594.
[71] Malmstrom J, Christophersen C, Frisvad J C. Secondary metabolites characteristic ofPenicillium citrinum, Penicillium steckii and related species. Phytochemistry,2000,54:301~309.
[72] Watanabe A, Ono Y, Fujii I, et al, Product identification of polyketide synthase coded byAspergillus nidulans wA gene. Tetrahedron Lett.,1998,39,7733~7736.
[73] Sorensen J L, Aveskamp M M, Thrane U, et al. Chemical characterization of Phomapomorum isolated from Danish maize. International Journal of Food Microbiology,2010,136:310~317.
[74] Kimura T, Nishida M, Kuramochi K, et al. Novel azaphilones, kasanosins A and B, which arespecific inhibitors of eukaryotic DNA polymerases β and λ from Talaromyces sp. Bioorg.Med. Chem.,2008,16:4594~4599.
[75] Hayashi H, Oka Y, Kai K, et al. New chrodrimanin congeners, chrodrimanins D-H, fromYO-2of Talaromyces sp. Biosci. Biotechnol. Biochem.,2012,76(9):1765~1768.
[76] Tomikawa T, Shin-Ya K, Furihata K, et al. Rasfonin, a new apoptosis inducer inras-dependent cells from Talaromyces sp. J. Antibiot.,2000,53(8):848~850.
[77] Zhang W, Krohn K, Ullah Z, et al. New mono-and dimeric members of the secalonic acidfamily: Blennolides A–G isolated from the fungus Blennoria sp. Chem. Eur. J.,2008,14:4913~4923.
[78]蒋亭，田黎，郭爱华等，黄海葵附生真菌Penicillium thomii的化学成分。药学学报，2002,37(40):271~274.
[79] Steyn P S. The isolation, structure and configuration of secalonic acid D, the toxic metaboliteof Penicillium oxalicum. Tetrahedon,1970,26(1):51~57.
[80] Steffens J C, Robeson D J. Secalonic acid A, a vivotoxin in pink root-infected onion.Phytochemistry,1987,26(6):1599~1602.
[81] Howard C C, Johnstone R A W. Fungal Metabolites. Part1. Stereochemical features andmass spectrometry of secalonic acids. J. Chem. Soc., Perkin Trans.1: Organic andBio-Organic Chemistry,1973,(18):2033~2036.
[82] Franck B, Gottschalk E M, Ohnsorge U, et al. Ergot dyes. XII. Separation, structure, andabsolute configuration of diastereoisomeric secalonic acids A, B, and C. Chemische Berichte,1966,99(12):3842~3862.
[83] Kurobane I, Vining L C, Mcinnes A G. A new secalonic acid. Linkage betweentetrahydroxanthone units determined from deuterium isotope13C chemical shifts.Tetrahedron Lett.,1978,47:4633~4636.
[84] Kumagai H, Amemiya M, Naganawa H, et al. Biosynthesis of antitumor antibiotic, cytogenin.J. Antibiot.,1994,47(4):440~446.
[85] Kashiwada Y, Nonaka G I, Nishioka I. Studies on Rhubarb (Rhei Rhizoma). V. Isolation andcharacterization of chromone and chromanone derivatives. Chem. Pharm. Bull.,1984,32(9):3493~3500.
[86] Aly A H, Edrada-Ebel R A, Indriani I D, et al. Cytotoxic metabolites from the fungalendophyte Alternaria sp. and their subsequent detection in its host plant Polygonumsenegalense. J. Nat. Prod.,2008,71:972~980.
[87]杨志钧，殷瑜，王志强等，一株马兜铃内生真菌Colletotrichum sp.代谢产物中细胞毒活性成分的研究。天然产物研究与开发,2012,24:329~332.
[88] Tan N, Tao Y W, Pan J H, et al. Isolation, structure elucidation, and mutagenicity of fouralternariol derivatives produced by the mangrove endophytic fungus No.2240. Chem. Nat.Com.,2008,44(3):296~300.
[89] Pfeiffer E, Schebb N H, Podlech J, et al. Novel oxidative in vitro metabolites of themycotoxins alternariol and alternariol methyl ether. Mol. Nutr. Food Res.,2007,51:307~316.
[90]董丁，王淮滨，李广义。石灰菌代谢产物的化学研究(I).天然产物研究与开发。1992,4(2):44~47
[1] Fattorusso E, Luciano P, Taglialatela-Scafati O, et al. Chloroscabrolides, chlorinatednorcembranoids from the Indonesian soft coral Sinularia sp. Tetrahedron,2011,67(41):7983~7988.
[2]秦铭俐，李晓明，王斌贵。多指软珊瑚Sinularia numerosa中的倍半萜类化学成分[J].海洋与湖沼.2007,40(5):540~543.
[3] Sheu J H, Chang K C, Duh C Y. A cytotoxic5α,8α-epidioxysterol from a soft coral Sinulariaspecies. J. Nat. Prod.,2000,63(1):149~151.
[4] Ojika M, Islam M K, Shintani T, et al. Three new cytotoxic acylspermidines from the softcoral Sinularia sp. Bio. Biote. Bio.,2003,67(6):1410~1412.
[5] Choi Y H, Schmitz F J. Cytotoxic acylated spermidine from a soft coral Sinularia sp. J. Nat.Prod.,1997,60(5):495~496.
[6]何细新,杨若林,苏镜娱。鹿角短指软珊瑚的次生代谢产物研究.中山大学学报(自然科学版).2002,41(2):114~116.
[7] Chen B W, Chang S M, Huang C Y, et al. Hirsutosterols A–G, polyoxygenated steroids from aFormosan soft coral Cladiella hirsute. Org. Biomol. Chem.,2011,9:3272~3278.
[8] Moss G P. Nomenclature of steroids. Pure Appl. Chem.,1989,61(10):1783~1822.
[9] Migliuolo A, Piccialli V, Sica D. Two new9,11-secosterols from the marine sponge Spongiaofficinalis. Synthesis of9,11-seco-3β,6α,11-trihydroxy-5α-cholest-7-en-9-one. Steroids,1992,57(7):344~347.
[10] Ioannou E, Abdel-Razik A F, Alexi X, et al.9,11-Secosterols with antiproliferative activityfrom the gorgonian Eunicella cavolini. Bioorg. Med. Chem.,2009,17(13):4537~4541.
[11] Aknin M, Costantino V, Mangoni A, et al. New9,11-secosterols from gorgoniaSubergorgia suberosa of the Indian Ocean. Steroids,1998,63(11):575~578.
[12] Li L Y, Deng Z W, Fu H Z, et al.6-Hydroxy-4-en-3-one sterols from the marine spongeIotrochoto birotulata. Journal of Asian Natural Products Research,2005,7(2):115~120.
[13] Anjaneyulu A S R, Rao N S K, Venugopal M J R V. A novel furanosesquiterpenoid from thesoft coral Lobophytum catalai Tixier Durivault of the Andaman and Nicobar Islands. Indian J.Chem. Sect B: Organic Chemistry Including Medicinal Chemistry,1996,35B(10):1001~1003.
[14] Zhang H J, Tan G T, Santarsiero B D, el al. New Sesquiterpenes from Litsea verticillata. J.Nat. Prod.,2003,66(5):609~615.
[15] Kobayashi M. Marine terpenes and terpenoids. Part18. First natural α-Tocopherol andα-Tocopheryl quinone derivatives with an oxygenated side chain, isolated from the soft coralSinularia mayi. J. Chem. Res.(S),1994,12:494~495.
[16]赵君，戴丽香，雷婷等，中药五灵脂的化学成分研究。天然产物研究与开发，2010,22:541~543.
[17] Kernan M R, Cambie R C, Bergquist P R. Chemistry of sponges, VIII. Anomoian A, abromotyrosine derivative from Anomoianthella popeae. J. Nat. Prod.1990,53(3):720~723.
[18] Ciminiello P, Costantino V, Fattorusso E, et al. Chemistry of verongida sponges. Constituentsof the caribbean sponge aplysina fistularis forma fulva. J. Nat. Prod.,1994,57(6):705~712.
[19] Chowdhury B K, Chakrabory D P.3-formyl indole from Murraya exotica. Phytochemistry,1971,10(5):481~483.
[20] Moyer M P, Shiurba J F, Rapoport H. Metal-halogen exchange of bromoindoles. A route tosubstituted indoles. J. Org. Chem.,1986,51(26):5106~5110.
[21] Abou-Shoer M I, Shaala L A, Youssef D T A, et al. Bioactive Brominated Metabolites fromthe Red Sea Sponge Suberea mollis. J. Nat. Prod.,2008,71:1464~1467.
[22] Andersen R J, Faulkner D J. Novel antibiotic from a sponge of the genus Verongia.Tetrahedron Lett.,1973,(14):1175~1178.
[23] Venkateswarlu Y, Rao M R, Venkatesham U. A new dibromotyrosine-derived metabolitefrom the sponge Psammaplysilla purpurea. J. Nat. Prod.,1998,61(11):1388~1389.
[24] Rogers E W, Molinski T F. Highly Polar Spiroisoxazolines from the Sponge Aplysina fulva. J.Nat. Prod.,2007,70:1191~1194.
[25] Radwan M M, Manly S P, El Sayed K A, et al. Sinulodurins A and B, Antiproliferative andAnti-invasive Diterpenes from the Soft Coral Sinularia dura. J. Nat. Prod.,2008,71:1468~1471.
[26] Molina-Salinas G M, Rivas-Galindo V M, Said-Fernandez S, et al. Stereochemical analysis ofLeubethanol, an anti-TB-active serrulatane, from Leucophyllum frutescens. J. Nat. Prod.,2011,74:1842~1850.
[27] Yamada K, Ujiie T, Yoshida K, et al. Sinulobatins A~D, New Amphilectane-typediterpenoids from the Japanese Soft Coral Sinularia nanolobata. Tetrahedron,1997,53(13):4569~4578.
[28]孟丽媛，李秀保，张文等，短指软珊瑚中的生态活性物质。药学实践杂志，2010,28(4):274~278.
[29] Qiu Y, Qi S, Zhang S, et al. New polyoxygenated steroids from the South China Seagorgonian Echinogorgia aurantiaca. Pharmazie,2006,61(7):645~648.
[30] Shen Y C, Prakash C V S, Chang Y T. Two new polyhydroxysteroids from the gorgonian Isishippuris. Steroids,2001,66(9):721~725.
[31] Tanaka J, Trianto A, Musman M, et al. New polyoxygenated steroids exhibiting reversal ofmultidrug resistance from the gorgonian Isis hippuris. Tetrahedron,2002,58(32):6259~6266.
[32] Chang C H, Wen Z H, Wang S K, et al. New anti-inflammatory steroids from the Formosansoft coral Clavularia viridis. Steroids,2008,73(5):562~567.
[33] Jia R, Guo Y W, Mollo E, et al. Two new polyhydroxylated steroids from the Hainan SoftCoral Sinularia sp.. Helv. Chim. Acta.,2006,89(7):1330~1336.
[34] Ramesh P, Venkateswarlu V. Novel steroid constituents of the soft coral Sinularia dissecta.Steroids,1999,64(11):785~789.
[35] Vanisree M, Subbaraju G V, Bheemasankara Rao C. Alcyonacean metabolites VII-chemicalconstituents of Lobophytum denticulatum and Lobophytum strictum of the Indian Ocean. J.Asian Nat. Prod. Res.,2000,2(2):87~95.
[36] Umeyama A, Shoji N, Ozeki M, et al. Sarcoaldesterols A and B, two new polyhydroxylatedsterols from the soft coral Sarcophyton sp. J. Nat. Prod.,1996,59(9):894~895.
[37] Notaro G, Piccialli V, Sica D.3β,5α,6β-trihydroxylated sterols with a saturated nucleus fromtwo populations of the marine sponge Clzona copiosa. J. Nat. Prod.,1991,54(6):1570~1575.
[38] Prakasa Rao T S, Sarma N S, Murthy Y L N, et al. New polyhydroxy sterols from the marinesponge Callyspongia fibrosa (Ridley&Dendly). Tetrahedron Lett.,2010,51(27):3583~3586.
[39] Roccatagliata A J, Maier M S, Seldes A M. A novel marine steroidal sulfate from the starfishLuidza ludwzgi. J. Nat. Prod.,1995,58(12):1941~1944.
[40] Iorizzi M. Chemical and biological investigation of the polar constituents of the starfishLuzdza clathrata, collected in the gulf of Mexico. J. Nat. Prod.,1995,58(5):653~671.
[41] Finamore E, Minale L, Riccio R, et al. Novel marine polyhydroxylated steroids from thestarfish Myxoderma platyacanthum. J. Org. Chem.,1991,56(3):1146~1153.
[42]黄建设，李庆欣，吴军等。粗吻海龙化学成分的研究。中草药，2004,35(5):485~487.
[43]林文瀚，马爱英，季宇彬。中国南海软珊瑚化学成分Sinularia sp.的研究。哈尔滨商业大学学报，自然科学版，2006,22(2),1~3.
[44] Chen W T, Li Y, Guo Y W. Terpenoids of Sinularia soft corals: chemistry and bioactivity.Acta Pharmaceutica Sinica B.2012,2(3):227~237.
[45] Ettouati W S, Jacobs R S. Effect of pseudopterosin A on cell division, cell cycle progression,and DNA and protein synthesis in cultured sea urchin embryos. Mol. Pharmacol.1987,31(5):500~505.
[46](a) Fenical W. Marine soft corals of the genus Pseudopterogorgia: a resource for novelanti-inflammatory diterpenoids. J. Nat. Prod.,1987,50(6):1001~1008.(b) Rodriguez A D.The natural products chemistry of West Indian gorgonian octocorals. Tetrahedron,1995,51(16):4571~4618.
[47] Look S A, Fenical W, Matsumoto G K, et al. The pseudopterosins: a new class ofanti-inflammatory and analgesic diterpene pentosides from the marine sea whipPseudopterogorgia elisabethae (Octocorallia). J. Org. Chem.,1986,51(26):5140~5145.
[48] Roussis V, Wu Z, Fenical W, et al. New anti-inflammatory pseudopterosins from the marineoctocoral Pseudopterogorgia elisabethae. J. Org. Chem.,1990,55(16):4916~4922.
[49] Ata A, Kerr R G, Moya C E, et al. Identification of anti-inflammatory diterpenes from themarine gorgonian Pseudopterogorgia elisabethae. Tetrahedron,2003,59(23):4215~4222.
[50] Look S A, Fenical W. The seco-pseudopterosins, new anti-inflammatory diterpene-glycosidesfrom a Caribbean gorgonian octocoral of the genus Pseudopterogorgia. Tetrahedron,1987,43(15):3363~3370.
[51] Rodriguez I I, Shi Y P, Garcia O J, et al. New Pseudopterosin and seco-Pseudopterosinditerpene glycosides from two Colombian Isolates of Pseudopterogorgia elisabethae andtheir diverse biological activities. J. Nat. Prod.,2004,67:1672~1680.
[52] Coleman A C, Kerr R G. Radioactivity-guided isolation and characterization of the bicyclicpseudopterosin diterpene cyclase product from Pseudopterogorgia elisabethae. Tetrahedron,2000,56:9569~9574.
[53] Ferns T A, Kerr R G. Identification of amphilectosins as key intermediates in pseudopterosinbiosynthesis. J. Org. Chem.,2005,70(16):6152~6157.
[54] Tanaka J, Ogawa N, Liang J, et al. Helioporins: bioactive diterpenes from the blue coralHeliopora coerulea. Tetrahedron,1993,49(4):811~822.
[55](a) Look S A, Fenical W, Jacobs R S, et al. The pseudopterosins: anti-inflammatory andanalgesic natural products from the sea whip Pseudopterogorgia elisabethae. Proc. Nat. Acad.Sci. USA,1986,83(17):6238~6240.(b) Harvis C A, Burch M T, Fenical W. New marinediterpenoids, including a unique hydroperoxide, from a Caribbean gorgonian coral of thegenus Pseudopterogorgia. Tetrahedron Lett.,1988,29(35):4361~4364.(c) Rodriguez A D,Ramirez C, Rodriguez I I. Elisabatins A and B: New amphilectane-type diterpenes from theWest Indian sea whip Pseudopterogorgia elisabethae. J. Nat. Prod.,1999,62(7):997~999.(d) Duque C, Puyana M, Castellanos L, et al. Further studies on the constituents of thegorgonian octocoral Pseudopterogorgia elisabethae collected in San Andres and Providenciaislands, Colombian Caribbean: isolation of a putative biosynthetic intermediate leading toerogorgiaene. Tetrahedron,2006,62(17):4205~4213.
[56](a) Baker J T, Wells R J, Oberhaensli W E, et al. A new diiscoyanide of novel ring structurefrom a sponge. J. Am. Chem. Soc.,1976,98(13):4010~4012.(b) Wratten S J, Faulkner D J,Hirotsu K, et al. Diterpenoid isocyanides from the marine sponge Hymeniacidon amphilecta.Tetrahedron Lett.,1978,(45):4345~4348.(c) Kazlauskas R, Murphy P T, Well R J, et al.New diterpene isocyanides from a sponge. Tetrahedron Lett.,1980,21(3):315~318.(d)Molinski T F, Faulkner D J, Van Duyne G D, et al. Three new diterpene isonitriles from aPalauan sponge of the genus Halichondria. J. Org. Chem.,1987,52(15):3334~3337.(e)Koenig G M, Wright A D, Angerhofer C K. Novel potent antimalarial diterpene isocyanates,isothiocyanates, and isonitriles from the tropical marine sponge Cymbastela hooperi. J. Org.Chem.,1996,61(10):3259~3267.(f) Wattanapiromsakul C, Chanthathamrongsiri N,Bussarawit S, et al.8-Isocyanoamphilecta-11(20),15-diene, a new antimalarial isonitrilediterpene from the sponge Ciocalapata sp. Can. J. Chem,2009,87(5):612~618.(g)Chanthathamrongsiri N, Yuenyongsawad S, Wattanapiromsakul C, et al. BifunctionalizedAmphilectane Diterpenes from the Sponge Stylissa cf. massa. J. Nat. Prod.,2012,75(4):789~792.
[57] Wang S K, Dai C F, Duh C Y. Cytotoxic pregnane steroids from the Formosan soft coralStereonephthya crystalliana. J. Nat. Prod.,2006,69(1):103~106.
[58] Qi S H, Zhang S, Huang J S, et al. Complete1H and13C NMR assignments of four newsteroidal glycosides from a gorgonian coral Junceella juncea. Magn. Reson. Chem.,2005,43(3):266~268.
[59] Szendi Z, Forgo P, Sweet F. Complete1H and13C NMR spectra of pregnenolone. Steroids,1995,60:442~446.
[60] Wong F F, Chen C Y, Chen T H, et al. Synthesis of3α-hydroxy-21-(1′-imidazolyl)-3β-methoxylmethyl-5α-pregnan-20-one via lithium imidazole with17α-acetylbromopregnanone.Steroids,2006,71:77~82.
[61] Viger A, Coustal S, Marquet A. A reinvestigation of the mechanism of Pseudomonastestosteroni Δ5-3-ketosteroid isomerase. J. Am. Chem. Soc.,1981,103(2):451~458.
[62] Della Greca M, Mangoni L, Molinaro A, et al. Studies on aquatic plants. XIII.5β,8β-Epidioxyergosta-6,22-dien-3β-ol from Typha latifolia. Gazz. Chim. Ital.,1990,120(6):391~392.
[63] Seo Y, Rho J R, Cho K W, et al. Isolation of epidioxysteroids from a Sponge of the GenusTethya. Bull. Korean Chem. Soc.,1997,18(6):631~635.
[64] Ioannoua E, Abdel-Razik A F, Zervouc M, et al.5α,8α-Epidioxysterols from the gorgonianEunicella cavolini and the ascidian Trididemnum inarmatum: Isolation and evaluation oftheir antiproliferative activity. Steroids,2009,74:73~80.
[65] Gauvin A, Smadja J, Aknin M, et al. Isolation of bioactive5α,8α-epidioxy sterols from themarine sponge Luffariella cf. variabilis. Can. J. Chem.,2000,78:986~992.
[66] Kawai S, Takada Y, Tsuchida S, et al. Sterols from bivalves Calyptogena soyoae andBathymodiolus septemdierum living in deep sea. Fisheries science,2007,73:902~906.
[67]吴少华，陈有为，杨丽源等。印度块菌的化学成分研究。中草药，2009,40(8):1211~1214.
[68] Chao C H, Hsieh C H, Chen S P, et al. Novel cyclic sesquiterpene peroxides from theFormosan soft coral Sinularia sp. Tetrahedron Letters,2006,47:2175~2178.
[69] Bowden B F, Coll J C, Silva E D, et al. Studies of Australian Soft Corals. XXXI*Novelfuranosesquiterpenes from several Sinularian Soft Corals (Coelenterata, Octocorallia,Alcyonacea). Aust. J. Chem.,1983,36:371~376.
[70] Bortolotto M, Braekman J C, Daloze D, et al. Chemical studies of marine invertebrates.XVIIIFour novel polyhydroxylated steroids from Sinularia dissecta (Coelenterata, Octocorallia,Alcyonacea). Bull. Soc. Chim. Belg.,1976,85:27~34.
[71] Byon CY, Kimball H L, Gut M. Synthesis of7α-Hydroxycholesterol. Steroids,1977,30(3):419~423.
[72] DellaGreca M, Marino C D, Zarrelli A, et al. Isolation and phytotoxicity of apocarotenoidsfrom Chenopodium album. J. Nat. Prod.,2004,67:1492~1495.
[73] Miyase T, Ueno A, Takizawa N, et al. Studies on the glycosides of Epimedium grandiflorumMORR. var. thunbergianum (MIQ.) NAKAI. I. Chem. Pharm. Bull.,1987,35(3):1109~1117.
[74] Shiraga Y, Okano K, Akira T, et al. Structures of potent antiulcerogenic compounds fromCinnamomum cassia. Tetrahedron,1988,44(15):4703~4711.
[75] Doi Y, Ishibashi M, Yamaguchi N, et al. Isolation of apo-9’-fucoxanthinone from thecultured marine dinoflagellate Amphidinium sp. J. Nat. Prod.,1995,58(7):1097~1099.
[76] Mori K, Ooi T, Hiraoka M, et al. Fucoxanthin and its metabolites in edible brown algaecultivated in deep seawater. Mar. Drugs,2004,2(2):63~72.
[77] Shaw B A, Andersen R J, Harrisson P J. Feeding deterrence properties ofapo-fucoxanthinoids from marine diatoms. I. Chemical structures of apo-fucoxanthinoidsproduced by Phaeodactylum tricornutum. Mar. Biol.,1995,124(3):467~472.
[78] Shaw B A, Andersen R J, Harrison P J. Feeding deterrent and toxicity effects ofapo-fucoxanthinoids and phycotoxins on a marine copepod (Tigriopus californicus). Mar.Biol.,1997,128(2):273~280.
[79] Hattab M E, Culioli G, Valls R, et al. Apo-fucoxanthinoids and loliolide from the brown algaCladostephus spongiosus f. verticillatus (Heterokonta, Sphacelariales). Biochem. Syst. Ecol.,2008,36:447~451.